Structural Classification of Complex Molecules by Artificial Intelligence Techniques

Algorithms for classification and taxonomy bases on criteria, e.g., information entropy. The feasibility of replacing a given molecule by similar ones in the composition of a complex drug is studied. Some local anaesthetics currently in use are classified using structural properties. In taxonomy the detailed comparison of the sequences of biomolecules, proteins or nucleic acids, allows the reconstruction of a molecular phylogenetic tree. The method is applied to the classifications of (1) indazolols (against Trichomonas vaginalis), (2) fullerenes and fullerite, (3) living and heat-inactivated lactic acid bacteria against cytokines, (4) phylogenesis of avian birds and 1918 influenza virus, (…

Applications of Bond-Based 3D-Chiral Quadratic Indices in QSAR Studies Related to Central Chirality Codification

The concept of bond-based quadratic indices is generalized to codify chemical structure information for chiral drugs, making use of a trigonometric 3D-chirality correction factor. In order to evaluate the effectiveness of this novel approach in drug design, we have modeled several well-known data sets. In particularly, Cramer's steroid data set has become a benchmark for the assessment of novel QSAR methods. This data set has been used by several researchers using 3D-QSAR approaches. Therefore, it is selected by us for the shake of comparability. In addition, to evaluate the effectiveness of this novel approach in drug design, we model the angiotensin-converting enzyme inhibitory activity o…

Valence Topological Charge-Transfer Indices for Dipole Moments

Valence topological charge-transfer (CT) indices are applied to the calculation of dipole moments. The dipole moments calculated by algebraic and vector semisums of the CT indices are defined. The combination of the CT indices allows the estimation of the dipole moments. The model is generalized for molecules with heteroatoms. The ability of the indices for the description of the molecular charge distribution is established by comparing them with the dipole moment of the valence-isoelectronic series of benzene and styrene. Two CT indices, μ v e c (vector semisum of vertex-pair dipole moments) and μ V v e c (valence μ v e c ) are proposed. μ v e c and μ V v e c are important for the predicti…

A Chemical Index Inspired by Biological Plastic Evolution:  Valence-Isoelectronic Series of Aromatics

Plastic evolution is a new perspective of the evolutionary process conjugating the effect, on one hand, of the acquired characters and, on the other, of the relationships that emerge among the principle of evolutionary indeterminacy, the principle of morphologic determination, and natural selection. Plastic evolution is applied to design the coordination index Ic. Ic is used to characterize the valence-isoelectronic series of cyclopentadiene, benzene, toluene, and styrene and compared to charge indices for dipole moment. The parameters needed to calculate Ic are minus the standard enthalpy of formation T, molecular surface area S, and molecular weight W. With the exception of the O heteromo…

Incorporation of Silica Nanospherical Particles into Epoxy-Amine Crosslinked Materials

Composites of silica nanospheres coated with crosslinked epoxy–amine were synthesised and examined by 29Si-magic-angle-spinning nuclear magnetic resonance spectroscopy, thermogravimetric analysis, Fourier transform infrared spectroscopy and scanning electron microscopy. The most representative fact is that epoxy-modified nanospheres lost less weight at high temperatures. At temperatures greater than 300°C the loss of weight for epoxy-modified nanospheres was rather lower than for unmodified nanospheres. This helped them to retain their structures, as the loss of weight can have adverse effects on network defects, due to the loss of crosslinks by unit of volume.

Calculations of organic-solvent dispersions of single-wall carbon nanotubes

The aqueous solubility Sw and 1-octanol–(Po), cyclohexane–(Pch), and chloroform–(Pcf) water partition coefficients are calculated. The properties of single-wall carbon nanotubes (SWNT) are related to the indices (n, m) designating the chiral vector. SWNTs are classified in zigzag (n, 0), armchair (n, n), and chiral (n, m). These properties permit classifying SWNTs according to (n, m). Correlations between (n2 + nm + m2)1/2, log Sw, log Po, log Pch, and log Pcf show that (n, m) are adequate indices. The (10,10) is the most abundant SWNT, presenting consistency between great kinetic stability, small Sw, and great {Po, Pch, Pcf}. The room temperature solubility of SWNTs is investigated in a va…

TOMOCOMD-CARDD descriptors-based virtual screening of tyrosinase inhibitors: evaluation of different classification model combinations using bond-based linear indices.

Abstract A new set of bond-level molecular descriptors (bond-based linear indices) are used here in QSAR (quantitative structure–activity relationship) studies of tyrosinase inhibitors, for finding functions that discriminate between the tyrosinase inhibitor compounds and inactive ones. A database of 246 compounds was collected for this study; all organic chemicals were reported as tyrosinase inhibitors; they had great structural diversity. This dataset can be considered as a helpful tool, not only for theoretical chemists but also for other researchers in this area. The set used as inactive has 412 drugs with other clinical uses. Twelve LDA-based QSAR models were obtained, the first six us…

<strong>Predicting Proteasome Inhibition using Atomic Weighted Vector and Machine Learning</strong>

Ubiquitin/Proteasome System (UPS) is a highly regulated mechanism of intracellular protein degradation and turnover. Through the concerted actions of a series of enzymes, proteins are marked for proteasomal degradation by being linked to the polypeptide co-factor, ubiquitin. The UPS participates in a wide array of biological functions such as antigen presentation, regulation of gene transcription and the cell cycle, and activation of NF-κB. Some researchers have applied QSAR method and machine learning in the study of proteasome inhibition (EC50(µmol/L)), such as: the analysis of proteasome inhibition prediction, in the prediction of multi-target inhibitors of UPP and in the prediction of p…

Fullerite crystal thermodynamic characteristics and the law of corresponding states.

The existence of single-wall carbon nanotubes in organic solvents in the form of clusters is discussed. A theory is developed based on a bundlet model, which enables describing the cluster-size distribution function. Comparison of calculated solubilities with experiments would permit obtaining energetic parameters, characterizing the interaction of a nanotube with its surrounding. Fullerenes and nanotubes are objects whose behaviour in many physical situations is characterized by peculiarities, which show up in that these systems represent the only soluble forms of carbon, what is related to their molecular structures. The fullerene molecule is a virtually uniform closed spherical-spheroida…

Discrete Derivatives for Atom-Pairs as a Novel Graph-Theoretical Invariant for Generating New Molecular Descriptors: Orthogonality, Interpretation and QSARs/QSPRs on Benchmark Databases.

This report presents a new mathematical method based on the concept of the derivative of a molecular graph (G) with respect to a given event (S) to codify chemical structure information. The derivate over each pair of atoms in the molecule is defined as ∂G/∂S(vi  , vj )=(fi -2fij +fj )/fij , where fi (or fj ) and fij are the individual frequency of atom i (or j) and the reciprocal frequency of the atoms i and j, respectively. These frequencies characterize the participation intensity of atom pairs in S. Here, the event space is composed of molecular sub-graphs which participate in the formation of the G skeleton that could be complete (representing all possible connected sub-graphs) or comp…

Effect of packing on the cluster nature of C nanotubes: An information entropy analysis

The possibility of the existence of single-wall carbon nanotubes (SWNTs) in organic solvents in the form of clusters is discussed. A theory is developed based on a bundlet model for clusters, which enables describing the distribution function of clusters by size. Comparison of the calculated values of solubility with experiments would permit obtaining energetic parameters characterizing the interaction of an SWNT with its surrounding, in a solid or solution. Fullerenes and SWNTs are unique objects, whose behaviour in many physical situations is characterized by remarkable peculiarities. Peculiarities in solutions show up first in that fullerenes and SWNTs represent the only soluble forms of…

Experimental Studies for Modelling the Phase Behaviour of Monomer/Polymer/Disc Composites

Nanoparticles do not stabilize the mixtures of epoxy monomer (prepolymer)/thermoplastic modifier (PS) and the ones of thermoplastic modifier dispersed within cured epoxy matrix. A small amount of thermoplastic co-polymer poly(styrene-b-methyl methacrylate) [P(S-b-MMA)] of MMA 4-22 wt.%, mixed with PS, makes compatible the mixtures with monomer epoxy precursor and cured epoxy matrix. The mixtures of cured epoxy matrix with thermoplastic consisting of PS and P(S-b-MMA), with nanofil 1%, are stable: the instability produced by the nanofil is overcome by the stability provided by the co-polymer. A model by Balazs' group to explain the phase behaviour of polymer/clay composites is extended.

Predicting antitrichomonal activity: A computational screening using atom-based bilinear indices and experimental proofs

Existing Trichomonas vaginalis therapies are out of reach for most trichomoniasis people in developing countries and, where available, they are limited by their toxicity (mainly in pregnant women) and their cost. New antitrichomonal agents are needed to combat emerging metronidazole-resistant trichomoniasis and reduce the side effects associated with currently available drugs. Toward this end, atom-based bilinear indices, a new TOMOCOMD-CARDD molecular descriptor, and linear discriminant analysis (LDA) were used to discover novel, potent, and non-toxic lead trichomonacidal chemicals. Two discriminant functions were obtained with the use of non-stochastic and stochastic atom-type bilinear in…

Comparative analysis of the electrostatics of the binding of cationic proteins to vesicles: Asymmetric location of anionic phospholipids

The role of electrostatics is studied in the adsorption of cationic proteins to zwitterionic phosphatidylcholine (PC) and anionic PC/phosphatidylglycerol (PG) mixed small unilamellarvesicles (SUVs). For model proteins the interaction is monitored vs. PG content at low ionic strength. The adsorption of lysozyme and myoglobin (isoelectric point, pl 7-11) is investigated in SUVs, along with changes of the fluorescence emission spectra of the cationic proteins, via their adsorption on SUVs. In the Gouy-Chapman formalism, the activity coefficient goes with the square of charge number. Deviations from the ideal model could indicate the asymmetric location of the anionic phospholipid in the bilaye…

New dimension indices for the characterization of the solvent-accessible surface

Event-based criteria in GT-STAF information indices: theory, exploratory diversity analysis and QSPR applications

Versatile event-based approaches for the definition of novel information theory-based indices (IFIs) are presented. An event in this context is the criterion followed in the "discovery" of molecular substructures, which in turn serve as basis for the construction of the generalized incidence and relations frequency matrices, Q and F, respectively. From the resultant F, Shannon's, mutual, conditional and joint entropy-based IFIs are computed. In previous reports, an event named connected subgraphs was presented. The present study is an extension of this notion, in which we introduce other events, namely: terminal paths, vertex path incidence, quantum subgraphs, walks of length k, Sach's subg…

New ligand-based approach for the discovery of antitrypanosomal compounds.

The antitrypanosomal activity of 10 already synthesized compounds was in silico predicted as well as in vitro and in vivo explored against Trypanosoma cruzi. For the computational study, an approach based on non-stochastic linear fingerprints to the identification of potential antichagasic compounds is introduced. Molecular structures of 66 organic compounds, 28 with antitrypanosomal activity and 38 having other clinical uses, were parameterized by means of the TOMOCOMD-CARDD software. A linear classification function was derived allowing the discrimination between active and inactive compounds with a confidence of 95%. As predicted, seven compounds showed antitrypanosomal activity (%AE > 7…

Atom- and Bond-Based 2D TOMOCOMD-CARDD Approach and Ligand-Based Virtual Screening for the Drug Discovery of New Tyrosinase Inhibitors

Two-dimensional atom- and bond-based TOMOCOMD-CARDD descriptors and linear discriminant analysis (LDA) are used in this report to perform a quantitative structure-activity relationship (QSAR) study of tyrosinase-inhibitory activity. A database of inhibitors of the enzyme is collected for this study, within 246 highly dissimilar molecules presenting antityrosinase activity. In total, 7 discriminant functions are obtained by using the whole set of atom- and bond-based 2D indices. All the LDA-based QSAR models show accuracies above 90% in the training set and values of the Matthews correlation coefficient (C) varying from 0.85 to 0.90. The external validation set shows globally good classifica…

Fractal dimension of zeolite catalysts

Atom—atom analyses of the geometric descriptors, topological indices and fractal dimension D are applied to active-site models of Br⊘nsted acid zeolites. The results are compared with those from the literature for rings and cavities. A method is tested similar to that used in previous works for crystal fragments. The results obtained are encouraging and the good quality of the analysis is clear from a comparison with cavity results. The active sites are modelled by sets of Al—OH—Si units. These bridges form 2–12 membered rings. Indices for the models are calculated. An analysis shows that the maximal Dsi contribution corresponds to the 6-ring, matching the maximal Dcavity. It is suggested t…

Molecular Classification of Pesticides Including Persistent Organic Pollutants, Phenylurea and Sulphonylurea Herbicides

Pesticide residues in wine were analyzed by liquid chromatography–tandem mass spectrometry. Retentions are modelled by structure–property relationships. Bioplastic evolution is an evolutionary perspective conjugating effect of acquired characters and evolutionary indeterminacy–morphological determination–natural selection principles; its application to design co-ordination index barely improves correlations. Fractal dimensions and partition coefficient differentiate pesticides. Classification algorithms are based on information entropy and its production. Pesticides allow a structural classification by nonplanarity, and number of O, S, N and Cl atoms and cycles; different behaviours depend …

Nucleotide's bilinear indices: Novel bio-macromolecular descriptors for bioinformatics studies of nucleic acids. I. Prediction of paromomycin's affinity constant with HIV-1 Ψ-RNA packaging region

A new set of nucleotide-based bio-macromolecular descriptors are presented. This novel approach to bio-macromolecular design from a linear algebra point of view is relevant to nucleic acids quantitative structure-activity relationship (QSAR) studies. These bio-macromolecular indices are based on the calculus of bilinear maps on Re(n)[b(mk)(x (m),y (m)):Re(n) x Re(n)--Re] in canonical basis. Nucleic acid's bilinear indices are calculated from kth power of non-stochastic and stochastic nucleotide's graph-theoretic electronic-contact matrices, M(m)(k) and (s)M(m)(k), respectively. That is to say, the kth non-stochastic and stochastic nucleic acid's bilinear indices are calculated using M(m)(k)…

Ideas in the History of Nano/Miniaturization and (Quantum) Simulators: Feynman, Education and Research Reorientation in Translational Science

Cultural history of nanominiaturization, computing, quantum computing and simulating is necessary to comprehend human character and place it in the whole of living beings. Ideas in the history of physics by Feynman, etc. are valued by the questions that generate. A series of questions, answers and hypothesis introduces the nature of the history of nanominiaturization, providing facts. Nanotechnology adds a third dimension to the periodic table of the elements. Thinking about computers was useful. It must do with learning computers possibilities and physics potential. Provisional conclusions follow. (1) Nature (space–time) is not classical but discrete; quantization is a different kind of ma…

Tyrosinase Enzyme: 1. An Overview on a Pharmacological Target

The tyrosinase enzyme (EC 1.14.18.1) is an oxidoreductase inside the general enzyme classification and is involved in the oxidation and reduction process in the epidermis. These chemical reactions that the enzyme catalyzes are of principal importance in the melanogenesis process. This process of melanogenesis is related to the melanin formation, a heteropolymer of indolic nature that provides the different tonalities in the skin and helps to the protection from the ultraviolet radiation. However, a pigment overproduction, come up by the action of the tyrosinase, can cause different disorders in the skin related to the hyperpigmentation. Several studies mainly focused on the characteristics …

Modelling Monomer/Disc Composites Phase Behaviour

Summary: A model developed by Balazs' group to explain the phase behaviour of polymer/clay composites is extended to obtain an expression for the free energy of polymer/thin disc mixtures. Phase diagrams for monomer/disc mixtures are built by minimizing the free energy and calculating the chemical potentials of the three system components. Via the comparison of the diagrams, it is studied the effects of nanodisc size and interaction parameters on mixture stability and attained morphology. The performed predictions between monomers and discs give criteria that advance the properties of the mixture. Changes in monomer concentration and interaction parameters provide a means to prevent van der…

Graphene and Fullenene Clusters

Interacting induced-dipoles polarization in code POLAR permits calculating molecular polarizability, which is tested with endohedral metallofullerenes Scn@Cm and clusters Cn (fullerene, graphene, GR). Polarizability identifies aggregates with dissimilar numbers of atoms and separates isomers. Results are of the same order of magnitude as reference computations performed with code PAPID. Polarizability bulk limit is estimated from Clausius–Mossotti relationship. Polarizability trend for clusters vs. size is unexpected: they are more polarizable than bulk. Theory yielded the same for small Sin, Gen and GanAsm; however, experiment oppositely deferred for larger Sin, GanAsm and GenTem. Smaller …

Information entropy-based classification of triterpenoids and steroids from Ganoderma

Abstract A set of 71 triterpenoid and steroid compounds from Ganoderma were periodically classified using a procedure based on information entropy with artificial intelligence. Six features were used in hierarchical order to classify the triterpenoids and steroids structurally. The phytochemicals belonging to the same group in the periodic table present similar antioxidant activity, and those compounds belonging to the same period exhibit maximum resemblance. The periodic classification is related to the experimental bioactivity and antioxidant potency data that are available in the literature: a steroid with a three-ketone group conjugated with two carbon–carbon double bonds in the right s…

Incorporation of Silica Nanospherical Particles in Epoxy–Amine Crosslinked Materials II. Dynamic Mechanical Measurements of Epoxy Matrix-Silica Nanocomposites

The mechanical strengths of epoxy composites reinforced with silica nanospheres, unfunctionalised or functionalised with either amine or epoxy groups, increase up to a proportion of 5 wt.% of filler, as reflected in a study of the shear storage modulus carried out in dynamic mechanical analysis. This improvement is observed in both glassy and rubbery states, moderately affecting the glass transition temperature of the material. From this percentage of strengthening substance the mechanical properties begin to deteriorate, but keeping (up to 10 wt.% of strengthening material), a greater storage modulus in shear than that of the pristine epoxy resin. A trend can be discerned as the percentag…

Comparative study to predict toxic modes of action of phenols from molecular structures.

Quantitative structure-activity relationship models for the prediction of mode of toxic action (MOA) of 221 phenols to the ciliated protozoan Tetrahymena pyriformis using atom-based quadratic indices are reported. The phenols represent a variety of MOAs including polar narcotics, weak acid respiratory uncouplers, pro-electrophiles and soft electrophiles. Linear discriminant analysis (LDA), and four machine learning techniques (ML), namely k-nearest neighbours (k-NN), support vector machine (SVM), classification trees (CTs) and artificial neural networks (ANNs), have been used to develop several models with higher accuracies and predictive capabilities for distinguishing between four MOAs. M…

Improved AMYR program: an algorithm for the theoretical simulation of molecular associations, including geometrical and topological characterization of the dimers.

Program AMYR, originally written by S. Fraga (University of Alberta, Canada), allows for the calculation of molecular associations using a pair-wise atom-atom potential. The interaction energy is evaluated through a 1/R expansion. Our improved version includes a dispersion energy term in the potential corrected by damping functions, the possibility of carrying out energy minimizations through variable metric methods, as well as the optional calculation of geometrical and topological indices. Program AMYR has been adapted also for high-performance computing and vectorization. An interactive version of the program carries out real-time molecular graphics showing simultaneously the energy prof…

QSPR Prediction of Retention Times of Methylxanthines and Cotinine by Bioplastic Evolution

High-performance liquid-chromatographic retention times of methylxanthines and cotinine in human plasma and urine are modelled by structure–property relationships. Bioplastic evolution is an evolutionary perspective conjugating the effect of acquired characters, and relations that emerge among the principles of evolutionary indeterminacy, morphological determination and natural selection. It is applied to design co-ordination index, which is used to characterize retentions of methylxanthines, etc. Parameters used to calculate co-ordination index are formation enthalpy, molecular weight and surface area. Morphological and co-ordination indices provide strong correlations. Effect of different…

Retrained Classification of Tyrosinase Inhibitors and “In Silico” Potency Estimation by Using Atom-Type Linear Indices

In this paper, the authors present an effort to increase the applicability domain (AD) by means of retraining models using a database of 701 great dissimilar molecules presenting anti-tyrosinase activity and 728 drugs with other uses. Atom-based linear indices and best subset linear discriminant analysis (LDA) were used to develop individual classification models. Eighteen individual classification-based QSAR models for the tyrosinase inhibitory activity were obtained with global accuracy varying from 88.15-91.60% in the training set and values of Matthews correlation coefficients (C) varying from 0.76-0.82. The external validation set shows globally classifications above 85.99% and 0.72 fo…

Ligand-based discovery of novel trypanosomicidal drug-like compounds: In silico identification and experimental support

Abstract Two-dimensional bond-based linear indices and linear discriminant analysis are used in this report to perform a quantitative structure–activity relationship study to identify new trypanosomicidal compounds. A database with 143 anti-trypanosomal and 297 compounds having other clinical uses, are utilized to develop the theoretical models. The best discriminant models computed using bond-based linear indices provides accuracies greater than 90 for both training and test sets. Our models identify as anti-trypanosomals five out of nine compounds of a set of already-synthesized substances. The in vitro anti-trypanosomal activity of this set against epimastigote forms of Trypanosoma cruzi…

Thorough evaluation of OECD principles in modelling of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives using QSARINS.

The human immunodeficiency virus is a lethal pathology considered as a worldwide problem. The search for new strategies for the treatment of this disease continues to be a great challenge in the scientific community. In this study, a series of 107 derivatives of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine, previously evaluated experimentally against HIV-I reverse transcriptase, was used to model antiretroviral activity. A model of linear regression, implemented in the QSARINS software, was developed with a genetic algorithm for variable selection. The fit of its parameters was good and exhaustive validation, according to the OECD regulatory principles, was performed. Also, the applica…

Non-stochastic quadratic fingerprints and LDA-based QSAR models in hit and lead generation through virtual screening: theoretical and experimental assessment of a promising method for the discovery of new antimalarial compounds

In order to explore the ability of non-stochastic quadratic indices to encode chemical information in antimalarials, four quantitative models for the discrimination of compounds having this property were generated and statistically compared. Accuracies of 90.2% and 83.3% for the training and test sets, respectively, were observed for the best of all the models, which included non-stochastic quadratic fingerprints weighted with Pauling electronegativities. With a comparative purpose and as a second validation experiment, an exercise of virtual screening of 65 already-reported antimalarials was carried out. Finally, 17 new compounds were classified as either active/inactive ones and experimen…

Molecular Classification of 5-Amino-2-Aroylquinolines and 4-Aroyl-6,7,8-Trimethoxyquinolines as Highly Potent Tubulin Polymerization Inhibitors

Algorithms for classification and taxonomy are proposed based on criteria as information entropy and its production. It is classified a series of 5-amino-2-aroylquinolines (AAQs) and 4-aroyl-6,7,8-trimethoxyquinolines (TMQs) combretastatin analogues for anti-cancer activity. 5-Amino-6-methoxy-2-aroylquinoline AAQ showed anti-proliferative activity more potent as compared to combretastatin A-4 (CA4), against various human cancer cell lines and a multidrug resistance (MDR) cancer cell line. On the basis of AAQ/TMQ structure–activity relationship new derivatives are designed. The AAQs/TMQs are classified using nine characteristic chemical properties in molecules. Many classification algorithms…

Pair potential calculation of molecular associations: a vectorized version

Abstract The program AMYRVF is a vectorized and largely modified version of a previous program called AMYR for calculating molecular associations by means of Fraga's pair-wise atom-atom potential. Three new minimization procedures have been implemented as well as other improvements such as the inclusion of new pair-wise dispersion energy terms with damping functions, and the calculation of topological indices. Benchmark tests have been carried out on an IBM 3090 150E VF; the timings for the new vector algorithms and for the standard scalar computations, as well as the dependence of the overall performance gain on the size of interacting systems are reported for the VS Fortran 2.4 compiler e…

Classification of flavonoid compounds by using entropy of information theory

A total of 74 flavonoid compounds are classified into a periodic table by using an algorithm based on the entropy of information theory. Seven features in hierarchical order are used to classify structurally the flavonoids. From these features, the first three mark the group or column, while the last four are used to indicate the row or period in a table of periodic classification. Those flavonoids in the same group and period are suggested to show maximum similarity in properties. Furthermore, those with only the same group will present moderate similarity. In this report, the flavonoid compounds in the table, whose experimental data in bioactivity and antioxidant properties have been prev…

Characterizing Cavities in Model Inclusion Fullerenes: A Comparative Study

Abstract: The fullerene-82 cavity is selected as a model system in order to test several methods for characterizing inclusion molecules. The methods are based on different technical foundations such as a square and triangular tessellation of the molecular surface, spherical tessellation of the molecular surface, numerical integration of the atomic volumes and surfaces, triangular tessellation of the molecular surface, and cubic lattice approach to the molecular volume. Accurate measures of the molecular volume and surface area have been performed with the pseudorandom Monte Carlo (MCVS) and uniform Monte Carlo (UMCVS) methods. These calculations serve as a reference for the rest of the meth…

Protein linear indices of the ‘macromolecular pseudograph α-carbon atom adjacency matrix’ in bioinformatics. Part 1: Prediction of protein stability effects of a complete set of alanine substitutions in Arc repressor

Abstract A novel approach to bio-macromolecular design from a linear algebra point of view is introduced. A protein’s total (whole protein) and local (one or more amino acid) linear indices are a new set of bio-macromolecular descriptors of relevance to protein QSAR/QSPR studies. These amino-acid level biochemical descriptors are based on the calculation of linear maps on R n [ f k ( x m i ) : R n → R n ] in canonical basis. These bio-macromolecular indices are calculated from the kth power of the macromolecular pseudograph α-carbon atom adjacency matrix. Total linear indices are linear functional on R n . That is, the kth total linear indices are linear maps from R n to the scalar R [ f k …

Computational Study of Nanosized Drug Delivery from Cyclodextrins, Crown Ethers and Hyaluronan in Pharmaceutical Formulations

Abstract The problem in this work is the computational characterization of cyclodextrins, crown ethers and hyaluronan (HA) as hosts of inclusion complexes for nanosized drug delivery vehicles in pharmaceutical formulations. The difficulty is addressed through a computational study of some thermodynamic, geometric and topological properties of the hosts. The calculated properties of oligosaccharides of D-glucopyranoses allow these to act as co-solvents of polyanions in water. In crown ethers, the central channel is computed. Mucoadhesive polymer HA in formulations releases drugs in mucosas. Geometric, topological and fractal analyses are carried out with code TOPO. Reference calculations are…

QSPR prediction of retention times of phenylurea herbicides by biological plastic evolution.

A simple/sensitive high-performance liquid chromatographic method, with ultraviolet (UV) detection, was developed for phenylurea-herbicide analysis, which involves preconcentration using solid-phase extraction. Mobile phase was acetonitrile/water at flow-rate of 1 mL.min-1 with direct UV absorbance detection at 210 nm. Analyte separation studied on a C18 column was applied successfully to herbicide analysis in soft drink's brands and tap water. Good linearity/repeatability was observed for all pesticides. Retention times increase as: metoxuron < monuron < diuron < matazachlor < linuron. They are modelled by structure-property relations. The effect of different types of features is analyzed:…

Prediction of Aquatic Toxicity of Benzene Derivatives to Tetrahymena pyriformis According to OECD Principles

Background: Many QSAR studies have been developed to predict acute toxicity over several biomarkers like Pimephales promelas, Daphnia magna and Tetrahymena pyriformis. Regardless of the progress made in this field there are still some gaps to be resolved such as the prediction of aquatic toxicity over the protozoan T. pyriformis still lack a QSAR study focused in accomplish the OECD principles. Methods: Atom-based quadratic indices are used to obtain quantitative structure-activity relationship (QSAR) models for the prediction of aquatic toxicity. Our models agree with the principles required by the OECD for QSAR models to regulatory purposes. The database employed consists of 392 substitut…

Calculation of partition coefficient and hydrophobic moment of the secondary structure of lysozyme

A method that permits a semiquantitative estimate of the partitioning of any solute between any two media is presented. As an example, the partition coefficients and hydrophobic moment of the secondary structure of lysozyme are calculated. Program GSCAP is written as a version of Pascal's solvent-dependent conformational analysis (SCAP) program. The dipole moments calculated for the helices are trebled with respect to that for the sheet. For helices, the main contribution to the water-accessible surface area is the hydrophobic term, while the hydrophilic part dominates in the sheet. Molecular globularity and the three studied partition coefficients differentiate between helices and sheet.

Solvent features of cluster single-wall C, BC2N and BN nanotubes, cones and horns

Graphical abstractDisplay Omitted Highlights? It is discussed single-wall carbon, BC2N and BN nanocones in organic solvents in cluster form. ? Theory is developed based on a cluster bundlet model describing distribution function by size. ? There is explanation in which (BC2N/BN-)SWNC free energy is combined from two components. ? Bundlet model enables describing the distribution function of (BC2N/BN-)SWNC clusters by size. ? From purely geometrical differences, bundlet and droplet models predict different behaviours. It is discussed the existence of single-wall carbon nanocones (SWNCs), especially nanohorns (SWNHs), and BC2N/boron nitride (BN) analogues in organic solvents in cluster form; …

Molecular Classification of N-Aryloxazolidinone-5-carboxamides as Human Immunodeficiency Virus Protease Inhibitors

Algorithms for classification and taxonomy are proposed in this chapter based information entropy (IE) and its production. The 38  N- aryloxazolidinone-5-carboxamides (NCAs), for human immunodeficiency virus (HIV) protease (PR) inhibition, are classified using seven characteristic chemical properties of different moieties: R 1/2 , R 3–6 on different phenyls and R 7 . Many classification algorithms are based on IE. When applying some procedures to moderate-sized sets, excessive number of results appear compatible with the data and suffer combinatorial explosion. However, after the equipartition conjecture (EC), one has a selection criterion among different variants that results from classifi…

Dynamic Mechanical Measurements of Epoxy Matrix-Silica Nanocomposites II

The mechanical properties of epoxy-silica nanocomposites have been studied; the silica nanosphere fillers used were un-functionalised, functionalised with amine, with epoxy, or a mixture of both kinds. Dynamic mechanical analysis measurements revealed an increase in the shear storage modulus, for all samples with a filler content of 3–5%. Improvements were observed in the glassy and rubbery states, without affecting the glass transition temperature of the materials. Above these strengthening percentages, the mechanical properties began to deteriorate, but in all cases they remained superior to those of the pristine epoxy resin. For low strengthening percentages, samples reinforced with bot…

Computing the Kekulé structure count for alternant hydrocarbons

A fast computer algorithm brings computation of the permanents of sparse matrices, specifically, molecular adjacency matrices. Examples and results are presented, along with a discussion of the relationship of the permanent to the Kekule structure count. A simple method is presented for determining the Kekule structure count of alternant hydrocarbons. For these hydrocarbons, the square of the Kekule structure count is equal to the permanent of the adjacency matrix. In addition, for alternant structures the adjacency matrix for N atoms can be written in such a way that only an N/2 × N/2 matrix need be evaluated. The Kekule structure count correlates with topological indices. The inclusion of…

New antitrichomonal drug-like chemicals selected by bond (edge)-based TOMOCOMD-CARDD descriptors.

Bond-based quadratic indices, new TOMOCOMD-CARDD molecular descriptors, and linear discriminant analysis (LDA) were used to discover novel lead trichomonacidals. The obtained LDA-based quantitative structure-activity relationships (QSAR) models, using nonstochastic and stochastic indices, were able to classify correctly 87.91% (87.50%) and 89.01% (84.38%) of the chemicals in training (test) sets, respectively. They showed large Matthews correlation coefficients of 0.75 (0.71) and 0.78 (0.65) for the training (test) sets, correspondingly. Later, both models were applied to the virtual screening of 21 chemicals to find new lead antitrichomonal agents. Predictions agreed with experimental resu…

Atom-based 3D-chiral quadratic indices. Part 2: prediction of the corticosteroid-binding globulinbinding affinity of the 31 benchmark steroids data set.

A quantitative structure-activity relationship (QSAR) study to predict the relative affinities of the steroid 'benchmark' data set to the corticosteroid-binding globulin (CBG) is described. It is shown that the 3D-chiral quadratic indices closely correlate with the measured CBG affinity values for the 31 steroids. The calculated descriptors were correlated with biological data through multiple linear regressions. Two statistically significant models were obtained when non-stochastic (R = 0.924 and s = 0.46) as well as stochastic (R = 0.929 and s = 0.46) 3D-chiral quadratic indices were used. A leave-one-out (LOO) approach to model validation is used here; the best results obtained in the cr…

A NEW TOOL FOR THE STUDY OF RESONANCE IN CHEMICAL EDUCATION

The objective of this study is to present a computer-based project, for which our program POLAR and our version of PAPID were written for the study of the subject of resonance in chemistry. Both algorithms allow a better didactic strategy and methodological adaptation for the study of molecular properties in chemical education. Teachers will find the options of POLAR and PAPID useful for demonstrations. It is still to be explored the methodological application of these computational programs enriching the present teaching techniques. Implementing new algorithms in learning situations is technically simple, but checking their usefulness in teaching practice is extraordinarily complex and req…

Using Chemical Structural Indicators for Periodic Classification of Local Anaesthetics

Algorithms for classification and taxonomy based on criteria as information entropy and its production are proposed. Some local anaesthetics, currently in use, are classified using five characteristic chemical properties of different portions of their molecules. Many classification algorithms are based on information entropy. When applying the procedures to sets of moderate size, an excessive number of results appear compatible with data and the number suffers a combinatorial explosion. However, after the equipartition conjecture one has a selection criterion between different variants resulting from classification between hierarchical trees. Information entropy and principal component anal…

Relations frequency hypermatrices in mutual, conditional and joint entropy-based information indices.

Graph-theoretic matrix representations constitute the most popular and significant source of topological molecular descriptors (MDs). Recently, we have introduced a novel matrix representation, named the duplex relations frequency matrix, F, derived from the generalization of an incidence matrix whose row entries are connected subgraphs of a given molecular graph G. Using this matrix, a series of information indices (IFIs) were proposed. In this report, an extension of F is presented, introducing for the first time the concept of a hypermatrix in graph-theoretic chemistry. The hypermatrix representation explores the n-tuple participation frequencies of vertices in a set of connected subgrap…

Net charge and polarizability of zeolitic Brønsted acidic sites

The interacting induced-dipoles polarization model, implemented in our program POLAR, is used for the calculation of the effective polarizability of the zeolitic bridged OH group, which results much higher than that of the free silanol group. A high polarizability is also calculated for the bridged OH group with a Si4+, in the absence of Lewis-acid promotion of silanol by Al3+. The crystal polarizability is estimated from the Clausius-Mossotti relationship. Siliceous zeolites are low-permittivity isolators. The interaction of a weak base with the zeolitic OH can be considered as a local bond. Only when cations are located in the zeolite micropore, next to tetrahedra that contain trivalent c…

Revealing the relationship between vegetable oil composition and oxidative stability: A multifactorial approach

Abstract A detailed composition analysis was performed for 22 diverse oils and fats and included determination of tocopherols (α, γ and δ), β-carotene, chlorophyll, total phenolic compounds (TPC) and fatty acid (FA) composition, as well as the determination of their oxidative stability (Rancimat test). Principal components analysis was applied to obtain an overview of the sample variations and to identify behavioural patterns. Linear regression correlations and a multiple linear regression model were performed to quantify the relationship between the composition of oils and fats and their oxidative stability. The TPC and saturated FA were the main individual factors that correlated positive…

Molecular polarizability of Si/Ge/GaAs semiconductors clusters

The interacting induced dipole polarization model implemented in our program for the calculation of molecular polarizabilities (POLAR) is used for the calculation of the molecular dipole-dipole polarizability ${\overline{\overline{α}}}$. POLAR is tested with Si$_{n}$, Ge$_{n}$ and Ga$_{n}$As$_{m}$ small clusters. The polarizability is an important quantity for the identification of clusters with different numbers of atoms and even for the separation of isomers. The results for the polarizability are in agreement with reference calculations performed with our version of the program PAPID (polarisabilites atomiques par interactions dipolaires) and with reference computations from Dr. J.R. Che…

Cooperativity of Protein Binding to Vesicles

Electrostatics role is studied in protein adsorption to phosphatidylcholine (PC) and PC/phosphatidylglycerol (PG) small unilamellar vesicles (SUVs). Protein interaction is monitored vs. PG content at low ionic strength. Adsorption of lysozyme, myoglobin and bovine serum albumin (BSA) isoelectric point (pI) is investigated in SUVs, along with changes in protein fluorescence emission spectra. Partition coefficients and cooperativity parameters are calculated. At pI, binding is maximum while at lower/higher pHs binding drops. In Gouy–Chapman model activity coefficient goes with square charge number, which deviations indicate asymmetric location of anionic lipid in the bilayer inner leaflet, in…

Nanostructures Cluster Models in Solution

The existence of Single-Wall C-Nanocones (SWNCs), especially nanohorns (SWNHs), and BC2N/Boron Nitride (BN) analogues in cluster form is discussed in solution in this chapter. Theories are developed based on models bundlet and droplet describing size-distribution function. The phenomena present unified explanation in bundlet in which free energy of (BC2N/BN-)SWNCs involved in cluster is combined from two parts: volume one proportional to the number of molecules n in cluster and surface one, to n1/2. Bundlet enables describing distribution function of (BC2N/BN-)SWNC clusters by size. From geometrical differences bundlet [(BC2N/BN-)SWNCs] and droplet (C60/B15C30N15/B30N30) predict dissimilar …

Atom-Based Quadratic Indices to Predict Aquatic Toxicity of Benzene Derivatives to &lt;i&gt;Tetrahymena pyriformis&lt;/i&gt;

The non-stochastic and stochastic atom-based quadratic indices are applied to develop quantitative structure-activity relationship (QSAR) models for the prediction of aquatic toxicity. The used dataset, consisting of 392 benzene derivatives for which toxicity data to the ciliate Tetrahymena pyriformis were available, is divided into training and test sets. The obtained multiple linear regression models are statistically significant (R2 = 0.787 and s = 0.347, R2 = 0.806 and s = 0.329, for non-stochastic and stochastic quadratic indices, respectively) and show rather good stability in a cross-validation experiment (q2 = 0.769 and scv = 0.357, q2 = 0.791 and scv = 0.337, correspondingly). In a…

tomocomd-camps and protein bilinear indices - novel bio-macromolecular descriptors for protein research: I. Predicting protein stability effects of a complete set of alanine substitutions in the Arc repressor

Descriptors calculated from a specific representation scheme encode only one part of the chemical information. For this reason, there is a need to construct novel graphical representations of proteins and novel protein descriptors that can provide new information about the structure of proteins. Here, a new set of protein descriptors based on computation of bilinear maps is presented. This novel approach to biomacromolecular design is relevant for QSPR studies on proteins. Protein bilinear indices are calculated from the kth power of nonstochastic and stochastic graph–theoretic electronic-contact matrices, and , respectively. That is to say, the kth nonstochastic and stochastic protein bili…

Compatibility between polystyrene copolymers and polymers in solution via hydrogen bonding

Abstract It has been applied the concept of improving miscibility, by introducing and optimizing the extent of intermolecular hydrogen-bonding interactions between two polymers. We select a commodity polymer such as polystyrene, to study the compatibility in chloroform with poly(vinyl pyridine) and poly(vinyl pyrrolidone), both considered as proton acceptors. In order to enhance polymer–polymer miscibility, polystyrene is slightly modified by copolymerization with methacrylic acid, in the first case, and with vinyl-phenol comonomer, in the second one. In this way, two series of polystyrene-based copolymers are synthesized and characterized bearing ca. 8% (w/w) of –OH groups. The miscibility…

Prediction of tyrosinase inhibition activity using atom-based bilinear indices.

A set of novel atom-based molecular fingerprints is proposed based on a bilinear map similar to that defined in linear algebra. These molecular descriptors (MDs) are proposed as a new means of molecular parametrization easily calculated from 2D molecular information. The nonstochastic and stochastic molecular indices match molecular structure provided by molecular topology by using the kth nonstochastic and stochastic graph-theoretical electronic-density matrices, M(k) and S(k), respectively. Thus, the kth nonstochastic and stochastic bilinear indices are calculated using M(k) and S(k) as matrix operators of bilinear transformations. Chemical information is coded by using different pair com…

QSAR models for tyrosinase inhibitory activity description applying modern statistical classification techniques: A comparative study

Abstract Cluster analysis (CA), Linear and Quadratic Discriminant Analysis (L(Q)DA), Binary Logistic Regression (BLR) and Classification Tree (CT) are applied on two datasets for description of tyrosinase inhibitory activity from molecular structures. The first set included 701 tyrosinase inhibitors (TI) that are used for performance of inhibitory and non-inhibitory activity and the second one is for potency estimation of active compounds. 2D TOMOCOMD-CARDD atom-based quadratic indices are computed as molecular descriptors. CA is used to “rational” design of training (TS) and prediction set (PS) but it shows of not being adequate as classification technique. On the first data, the overall a…

Computational discovery of novel trypanosomicidal drug-like chemicals by using bond-based non-stochastic and stochastic quadratic maps and linear discriminant analysis.

Herein we present results of a quantitative structure-activity relationship (QSAR) studies to classify and design, in a rational way, new antitrypanosomal compounds by using non-stochastic and stochastic bond-based quadratic indices. A data set of 440 organic chemicals, 143 with antitrypanosomal activity and 297 having other clinical uses, is used to develop QSAR models based on linear discriminant analysis (LDA). Non-stochastic model correctly classifies more than 93% and 95% of chemicals in both training and external prediction groups, respectively. On the other hand, the stochastic model shows an accuracy of about the 87% for both series. As an experiment of virtual lead generation, the …

Multiple Linear Regression to predict larvicidal activity against &lt;em&gt;Aedes aegypti &lt;/em&gt;mosquito

Vector-borne diseases are one of the important health problems in most tropical countries. Aedes aegypti is an important vector for transmission of dengue, yellow fever, chikungunya, arthritis, and Zika fever. According to the World Health Organization, it is estimated that Ae. aegypti causes 50 million infections and 25,000 deaths per year. The emerging scenario highlights that the eco-friendly and effective control measures for mosquito vectors is of crucial importance. One of the most effective vector control measures has been the use of larvicidal compounds however; this success was short lived due to development of resistance against them in many mosquito strains, ecological imbalance …

Interacting induced dipoles polarization model for molecular polarizabilities. Reference molecules, amino acids and model peptides

Abstract We outline a method for the calculation of molecular dipole ( μ ) and quadrupole ( Θ = ) moments and dipole–dipole polarizabilities ( α = ) which we have successfully applied to a series of reference molecules, amino acids and model peptides. The results for μ are in line with CPHF reference calculations. In particular, the calculated positive value of CO is in agreement with both experimental and CI calculations. The computation of ( α = ) has been performed by the interacting induced dipoles polarization model that calculates tensor effective anisotropic point polarizabilities (method of Applequist et al.). The POLAR program cannot be used as a black box. Some tests should be per…

Atom, atom-type, and total nonstochastic and stochastic quadratic fingerprints: a promising approach for modeling of antibacterial activity.

The TOpological MOlecular COMputer Design (TOMOCOMD-CARDD) approach has been introduced for the classification and design of antimicrobial agents using computer-aided molecular design. For this propose, atom, atom-type, and total quadratic indices have been generalized to codify chemical structure information. In this sense, stochastic quadratic indices have been introduced for the description of the molecular structure. These stochastic fingerprints are based on a simple model for the intramolecular movement of all valence-bond electrons. In this work, a complete data set containing 1006 antimicrobial agents is collected and presented. Two structure-based antibacterial activity classificat…

Bond-based bilinear indices for computational discovery of novel trypanosomicidal drug-like compounds through virtual screening

Two-dimensional bond-based bilinear indices and linear discriminant analysis are used in this report to perform a quantitative structure-activity relationship study to identify new trypanosomicidal compounds. A data set of 440 organic chemicals, 143 with antitrypanosomal activity and 297 having other clinical uses, is used to develop the theoretical models. Two discriminant models, computed using bond-based bilinear indices, are developed and both show accuracies higher than 86% for training and test sets. The stochastic model correctly indentifies nine out of eleven compounds of a set of organic chemicals obtained from our synthetic collaborators. The in vitro antitrypanosomal activity of …

Complexity, Emergence and Molecular Diversity via Information Theory

Numerous definitions for complexity have been proposed with little consensus. The definition here is related to Kolmogorov complexity and Shannon entropy measures. However, the price is to introduce context dependence into the definition of complexity. Such context dependence is an inherent property of complexity. Scientists are uncomfortable with such context dependence that smacks of subjectivity, which is the reason why little agreement is found on the meaning of the terms. In an article published in Molecules, Lin presented a novel approach for assessing molecular diversity based on Shannon information theory. A set of compounds is viewed as a static collection of microstates that can r…

Are most of the stationary points in a molecular association minima? Application of Fraga's potential to benzene-benzene

The importance of characterizing the stationary points of the intermolecular potential by means of Hessian eigenvalues is illustrated for the calculation of the benzene–benzene interaction using an atom-to-atom pair potential proposed by Fraga (FAAP). Two models, the standard one-center-per atom and another using three-centers-per atom due to Hunter and Sanders, are used to evaluate the electrostatic contributions and the results are compared. It is found in both cases that although using low-gradient thresholds allows optimization procedures to avoid many stationary points that are not true minima computing time considerations makes the usual procedure of using high-gradient thresholds [sa…

Extending Graph (Discrete) Derivative Descriptors to N-Tuple Atom-Relations

In the present manuscript, an extension of the previously defined Graph Derivative Indices (GDIs) is discussed. To achieve this objective, the concept of a hypermatrix, conceived from the calculation of the frequencies of triple and quadruple atom relations in a set of connected sub-graphs, is introduced. This set of subgraphs is generated following a predefined criterion, known as the event (S), being in this particular case the connectivity among atoms. The triple and quadruple relations frequency matrices serve as a basis for the computation of triple and quadruple discrete derivative indices, respectively. The GDIs are implemented in a computational program denominated DIVATI (acronym f…

Effect of elliptical deformation on molecular polarizabilities of model carbon nanotubes from atomic increments.

The interacting induced dipole polarization model implemented in our program POLAR is used for the calculation of the dipole-dipole polarizability alpha. The method is tested with single-wall carbon nanotube models as a function of nanotube radius and elliptical deformation. The results for polarizability follow the same trend as reference calculations performed with our version of the program PAPID. For the zigzag tubes, the polarizability is found to follow a remarkably simple law, that is, it varies as the inverse of the radius. A dramatic effect is also found with elliptical deformation. It is found that the polarizability and related properties can be modified continuously and reversib…

Interacting induced dipoles polarization model for molecular polarizabilities: application to benzothiazole (A)-benzobisthiazole (B) oligomers AB13A

Abstract We have outlined a method for the calculation of atomic net charges and molecular dipole-dipole,  α , dipole-quadrupole,  A , and quadrupole-quadrupole,  C , polarizabilities which we have successfully applied to benzothiazole (A)-benzobisthiazole (B) oligomers in the series AB1A to AB13A, and the results have been extrapolated to give predictions for polybenzobisthiazole. The calculation of  α ,  A and  C has been carried out by the interacting induced dipoles polarization model that calculates tensor effective anisotropic point polarizabilities (method of Applequist). The mean effective atomic αeffpolarizabilities for the monomeric unit are of the same order of magnitud…

An approach to identify new antihypertensive agents using Thermolysin as model: In silico study based on QSARINS and docking

Thermolysin is a bacterial proteolytic enzyme, considered by many authors as a pharmacological and biological model of other mammalian enzymes, with similar structural characteristics, such as angiotensin converting enzyme and neutral endopeptidase. Inhibitors of these enzymes are considered therapeutic targets for common diseases, such as hypertension and heart failure. In this report, a mathematical model of Multiple Linear Regression, for ordinary least squares, and genetic algorithm, for selection of variables, are developed and implemented in QSARINS software, with appropriate parameters for its fitting. The model is extensively validated according to OECD standards, so that its robust…

Cluster Origin of Solvent Features of Fullerenes, Single-Wall Carbon Nanotubes, Nanocones, and Nanohorns

This chapter discusses the existence of single-wall carbon nanocones (SWNCs), especially nanohorns (SWNHs) in organic solvents in the form of clusters. A theory is developed based on a bundlet model describing their distribution function by size. Phenomena have a unified explanation in bundlet model in which free energy of an SWNC, involved in a cluster, is combined from two components: a volume one, proportional to number of molecules n in a cluster, and a surface one proportional to n1/2. A bundlet model enables describing distribution function of SWNC clusters by size. From purely geometrical differences, bundlet (SWNCs) and droplet (fullerene) models predict different behaviours. The SW…

Study and comparison of interaction parameters and phase behavior of epoxy/polystyrene and epoxies copolymer polystyrene-b-poly(methyl methacrylate) blends

Thermodynamic studies in terms of phase separation behavior and interaction parameters, in mixtures of epoxy resins (thermoset materials) with thermoplastic additives, consisting of polystyrene (PS) or polystyrene-b-poly(methyl methacrylate) P(S-MMA) (with small proportion of MMA), have been carried out. It can be confirmed that the solubility of P(S-MMA) is an improvement on that of PS, with the prepolymer epoxy resins. Moreover, the interaction parameters are positive at temperatures in which phase separation is observed, but negative at temperatures in which the phase separation window disappears, in the corresponding phase diagram. POLYM. COMPOS., 2008. © 2008 Society of Plastics Engine…

Molecular polarizability of fullerenes and endohedral metallofullerenes

The interacting induced dipoles polarization model implemented in our program POLAR is used for the calculation of the molecular dipole µ and tensor quadrupole moments and also the dipole–dipole polarizability . The method is tested with Scn, Cn (fullerene and graphite) and endohedral Scn@Cm clusters. The polarizability is an important quantity for the identification of clusters with different numbers of atoms and even for the separation of isomers. The results for the polarizability are of the same order of magnitude as from reference calculations performed with our version of the program PAPID. The bulk limit for the polarizability is estimated from the Clausius–Mossotti relationship. The…

An Improved Force Field for O2, CO and CN Binding to Metalloporphyrins

Parametrization of a molecular-mechanics program to include terms specific for five- and six-coordinate transition metal complexes is applied to heme complexes. The principal new feature peculiar to five and six coordination is a term that represents the effect of electron-pair repulsion modified by the ligand electronegativity and takes into account the different possible structures of complexes. The model system takes into account the structural differences of the fixing centre in the haemoglobin subunits. The customary proximal histidine is added. The macrocycle heme IX is wholly considered in our model. The calculations show clearly that certain conformations of heme IX–histidine models…

Treatment of poly(styrene-co-methacrylic acid)/poly(4-vinylpyridine) blends in solution under liquid–liquid phase-separation conditions. A new method for phase-separation data attainment from viscosity measurements

Phase diagrams are contributed for polymer mixture systems in solution. One polymer has proton-acceptor character and the other has growing proton-donor nature, which is reflected in the phase diagrams. Usually, these diagrams are obtained from size-exclusion chromatographic (SEC) measurements. A totally novel application, which is exposed in this report, is the construction of the phase diagram from the viscometric experiments of polymer mixtures. The evaluated binodal or cloud-point isotherms so built agree well with those from SEC. The results indicate an augmentation in the dimensions of donor polymer B, in the presence of acceptor polymer C, intensifying with the concentration of C, wh…

Atom-based non-stochastic and stochastic bilinear indices: Application to QSPR/QSAR studies of organic compounds

The recently introduced bilinear indices are applied to the QSAR/QSPR studies of heteroatomic molecules. These novel atom-based molecular fingerprints are used to predict the boiling point of 28 alkyl-alcohols and partition coefficient, specific rate constant and antibacterial activity of 34 2-furylethylenes derivatives. The obtained models are statistically significant and show rather very good stability in a cross-validation experiment. The comparison with other approaches exposes a good behavior of our method in this QSPR studies. The obtained results suggest that with the present method, it is possible to obtain a good estimation of physical, chemical and physicochemical properties for …

Nature of FeIII–O2, FeII–CO and FeIII–CN complexes of hemoprotein models

Abstract Parametrization of a molecular-mechanics program to include terms specific for 5- and 6-coordinate transition metal complexes results in computer-simulated structures of hemo complexes. The principal new feature peculiar to 5- and 6-coordination is a term that measures the effect of electron-pair repulsion modified by the ligand electronegativity and takes into account the different structural possibilities. The work consists in the modification of program molecular mechanics for 5- and 6-coordination. The model system takes into account the structural differences of the fixing centre in the haemoglobin (Hb) subunits. The customary proximal histidine is added. The macrocycle hemo I…

Negatively cooperative binding of melittin to neutral phospholipid vesicles

Abstract The association of basic amphipathic peptides to neutral phospholipid membranes is investigated in terms of binding and partition models. The binding of native and modified melittin to egg-yolk phosphatidylcholine vesicles is studied by steady-state fluorescence spectroscopy. The effect of the ionic strength shows an enhancement of the association as the ionic strength increases. After correction for electrostatic effects by the Gouy–Chapman theory, the melittin binding isotherms could be described by a partition model. In terms of conventional binding mechanisms, which do not take into account electrostatic effects, this would correspond to a negative cooperativity. A plausible wa…

Bundlet Model of Single- Wall Carbon, BC2N and BN Nanotubes, Cones and Horns in Organic Solvents

Bundlet Model of Single- Wall Carbon, BC2N and BN Nanotubes, Cones and Horns in Organic Solvents The existence of Single-wall C-nanocones (SWNCs), especially nanohorns (SWNHs) and BC2N/Boron Nitride (BN) analogues is discussed in organic solvents in cluster form. A theory is developed based on the bundlet model, describing distribution function by size. The phenomena present unified explanation in the model, in which free energy of (BC2N/BN )SWNCs involved in cluster, is combined from two components: volume one proportional to the number of molecules n in cluster and surface one, to n1/2. The model enables describing distribution function of (BC2N/BN )SWNC clusters by size. From geometrical…

Information Theoretic Entropy for Molecular Classification: Oxadiazolamines as Potential Therapeutic Agents

In this review we present algorithms for classification and taxonomy based on information entropy, followed by structure-activity relationship (SAR) models for the inhibition of human prostate carcinoma cell line DU-145 by 26 derivatives of N-aryl-N-(3-aryl-1,2,4-oxadiazol-5-yl)amines (NNAs). The NNAs are classified using two characteristic chemical properties based on different regions of the molecules. A table of periodic properties of inhibitors of DU-145 human prostate carcinoma cell line is obtained based on structural features from the amine moiety and from the oxadiazole ring. Inhibitors in the same group and period of the periodic table are predicted to have highly similar propertie…

Discovery of novel anti-inflammatory drug-like compounds by aligning in silico and in vivo screening: The nitroindazolinone chemotype

In this report, we propose the combination of computational methods and in vivo primary screening in zebrafish larvae and confirmatory in mice models as a novel strategy to accelerate anti-inflammatory drug discovery. Initially, a database of 1213 organic chemicals with great structural variability - 587 of them anti-inflammatory agents plus 626 compounds with other clinical uses - was divided into training and test groups. Atom-based quadratic indices - a TOMOCOMD-CARDD molecular descriptors family - and linear discriminant analysis (LDA) were used to develop a total of 13 models to describe the anti-inflammatory activity. The best model (Eq. (13)) shows an accuracy of 87.70% in the traini…

3D-Chiral quadratic indices of the ‘molecular pseudograph’s atom adjacency matrix’ and their application to central chirality codification: classification of ACE inhibitors and prediction of σ-receptor antagonist activities

Quadratic indices of the 'molecular pseudograph's atom adjacency matrix' have been generalized to codify chemical structure information for chiral drugs. These 3D-chiral quadratic indices make use of a trigonometric 3D-chirality correction factor. These indices are nonsymmetric and reduced to classical (2D) descriptors when symmetry is not codified. By this reason, it is expected that they will be useful to predict symmetry-dependent properties. 3D-Chirality quadratic indices are real numbers and thus, can be easily calculated in TOMOCOMD-CARDD software. These descriptors circumvent the inability of conventional 2D quadratic indices (Molecules 2003, 8, 687-726. http://www.mdpi.org) and othe…

Quantitative Structure-Antioxidant Activity Models of Isoflavonoids: A Theoretical Study

Seventeen isoflavonoids from isoflavone, isoflavanone and isoflavan classes are selected from Dalbergia parviflora. The ChEMBL database is representative from these molecules, most of which result highly drug-like. Binary rules appear risky for the selection of compounds with high antioxidant capacity in complementary xanthine/xanthine oxidase, ORAC, and DPPH model assays. Isoflavonoid structure-activity analysis shows the most important properties (log P, log D, pKa, QED, PSA, NH + OH ≈ HBD, N + O ≈ HBA). Some descriptors (PSA, HBD) are detected as more important than others (size measure Mw, HBA). Linear and nonlinear models of antioxidant potency are obtained. Weak nonlinear relationship…

Cluster nature of the solvent features of single-wall carbon nanohorns

The existence of single-wall carbon nanotubes (SWNTs) in organic solvents, in the form of clusters, is discussed. A theory is developed based on a bundlet model for clusters, describing the distribution function of clusters by size. The phenomena have a unified explanation in the bundlet model of clusters, in accordance with which the free energy of an SWNT, involved in a cluster, is combined from two components: a volume one, proportional to the number of molecules n in a cluster, and a surface one proportional to n1/2. The bundlet model for clusters enables describing the distribution function of SWNT clusters by size. The droplet model is formally analogous to the one for fullerene clust…

QSAR of Natural Sesquiterpene Lactones as Inhibitors of Myb-dependent Gene Expression

Background Protein c-Myb is a therapeutic target. Some sesquiterpene lactones suppress Myb-dependent gene expression, which results in their potential anti-cancer activity. Material & methods Database ChEMBL is a representative of lactones for physicochemical and physiochemical properties. Data presented for 31 natural lactones are discussed in terms of quantitative structureactivity relationships with the objective to predict inhibitors of Myb-induced gene expression. Several constitutional descriptors are related to structure-activity. α-Methylene-γ-lactone groups enhance while OH functions worsen potency. The latter feature is in agreement with the fact that the more lipophilic the lacto…

Fractal Dimension of Transdermal-Delivery Drug Models: 4-Alkylanilines

Abstract The pathways that exist in porous membranes used to deliver drugs form fractal percolating paths. For a homologous series of 4-alkylanilines, the fractal dimension D is calculated as a model for transdermal-delivery drugs. Program TOPO is used for the calculation of the solvent-accessible surface AS, which is denoted by the centre of a probe, which is allowed to roll on the outside while maintaining contact with the bare molecular surface S. AS depends on the probe radius R. For 4-alkylanilines, the quadrupole moment Θ is doubled. The hydrophobic contribution to AS is doubled while its hydrophilic part remains constant. D increases 11%. Geometric descriptor and topological index re…

Elementary Polarizability of Sc/Fullerene/Graphene Aggregates and Di/Graphene–Cation Interactions

Elementary Polarizability of Sc/Fullerene/Graphene Aggregates and Di/Graphene–Cation Interactions Interacting induced-dipoles polarization in code POLAR allows molecular polarizability, which is tested with Scn/Cn [fullerene/ graphene (GR)]/Scn@Cm clusters. Polarizability sees clusters of unlike sizes, parting isomers. Bulk limit is estimated from Clausius– Mossotti relation. Clusters are more polarizable than the bulk. Theory yielded this for small Sin/Gen/GanAsm; however, experiment, reversely for larger Sin/GanAsm/GenTem. Smaller clusters need not act like middle: surface dangling bonds cause small-clusters polarizability that resembles metallic. Code AMYR models GR(2)– Mz+. A 24-atom pl…

(Co-)solvent selection for single-wall carbon nanotubes: best solvents, acids, superacids and guest-host inclusion complexes.

Analysis of 1-octanol-water, cyclohexane-water and chloroform (CHCl(3))-water partition coefficients P(o-ch-cf) allows calculation of molecular lipophilicity patterns, which show that for a given atom log P(o-ch-cf) is sensitive to the presence of functional groups. Program CDHI does not properly differentiate between non-equivalent atoms. The most abundant single-wall carbon nanotube (SWNT), (10,10), presents a relatively small aqueous solubility and large elementary polarizability, P(o-ch-cf) and kinetic stability. The SWNT solubility is studied in various solvents, finding a class of non-hydrogen-bonding Lewis bases with good solubility. Solvents group into three classes. The SWNTs in so…

Computational identification of chemical compounds with potential anti-Chagas activity using a classification tree

Chagas disease is endemic to 21 Latin American countries and is a great public health problem in that region. Current chemotherapy remains unsatisfactory; consequently the need to search for new drugs persists. Here we present a new approach to identify novel compounds with potential anti-chagasic action. A large dataset of 584 compounds, obtained from the Drugs for Neglected Diseases initiative, was selected to develop the computational model. Dragon software was used to calculate the molecular descriptors and WEKA software to obtain the classification tree. The best model shows accuracy greater than 93.4% for the training set; the tree was also validated using a 10-fold cross-validation p…

Identification In Silico and In Vitro of Novel Trypanosomicidal Drug-Like Compounds

Atom-based bilinear indices and linear discriminant analysis are used to discover novel trypanosomicidal compounds. The obtained linear discriminant analysis-based quantitative structure–activity relationship models, using non-stochastic and stochastic indices, provide accuracies of 89.02% (85.11%) and 89.60% (88.30%) of the chemicals in the training (test) sets, respectively. Later, both models were applied to the virtual screening of 18 in-house synthesized compounds to find new pro-lead antitrypanosomal agents. The in vitro antitrypanosomal activity of this set against epimastigote forms of Trypanosoma cruzi is assayed. Predictions agree with experimental results to a great extent (16/18…

Calculations on solvents and co-solvents of single-wall carbon nanotubes: Cyclopyranoses

Abstract (10,10) single-wall carbon nanotube (SWNT) presents consistency between relatively small solubility, and great partition coefficients and kinetic stability. Solubility of SWNTs is investigated in a variety of solvents, finding a class of non-hydrogen-bonding Lewis bases that provides good solubility. Electron affinity of d -glucopyranoses ( d -Glcpn) suggests colloids of negatively charged SWNTs in water.

Table of periodic properties of human immunodeficiency virus inhibitors

Classification algorithms are proposed based on information entropy. The feasibility of mixing a given human immunodeficiency virus (HIV) inhibitor with dissimilar ones is studied. The 31 inhibitors are classified by their structural chemical properties. Many classification algorithms are based on information entropy. An excessive number of results appear compatible with the data and suffer combinatorial explosion. However, after the equipartition conjecture one has a selection criterion. According to this conjecture, the best configuration is that in which entropy production is most uniformly distributed. The structural elements of an inhibitor can be ranked according to their inhibitory a…

Characterizing cavity-like spaces in active-site models of zeolites

A method for the calculation of fractal surfaces of crystals is presented. The fractal dimension of fragments of zeolites is computed. Results compare well with reference calculations performed with program GEPOL. The active site of Bronsted acid zeolites is modelled by sets of Al–OH–Si units. These units form 2–12-membered rings. Topological indices for the different active-site models are computed. The comparison of calculations performed with programs GEPOL and SURMO2 allows computing the model indices. The cavity-like globularity and rugosity show sharp discontinuities for the ring with 6 units. Most cavity-like spaces show no fractal character. However, the 6–8-ring cavity-like spaces …

Computational Identification of Chemical Compounds with Potential Activity against Leishmania amazonensis using Nonlinear Machine Learning Techniques.

Leishmaniasis is a poverty-related disease endemic in 98 countries worldwide, with morbidity and mortality increasing daily. All currently used first-line and second-line drugs for the treatment of leishmaniasis exhibit several drawbacks including toxicity, high costs and route of administration. Consequently, the development of new treatments for leishmaniasis is a priority in the field of neglected tropical diseases. The aim of this work is to develop computational models those allow the identification of new chemical compounds with potential anti-leishmanial activity. A data set of 116 organic chemicals, assayed against promastigotes of Leishmania amazonensis, is used to develop the the…

Characterizing cavities in model inclusion molecules: a comparative study

We have selected fullerene-60 and -70 cavities as model systems in order to test several methods for characterizing inclusion molecules. The methods are based on different technical foundations such as a square and triangular tessellation of the molecule taken as a unitary sphere, spherical tessellation of the molecular surface, numerical integration of the atomic volumes and surfaces, triangular tessellation of the molecular surface, and a cubic lattice approach to a molecular space. Accurate measures of the molecular volume and surface area have been performed with the pseudo-random Monte Carlo (MCVS) and uniform Monte Carlo (UMCVS) methods. These calculations serve as a reference for the…

Identification &lt;i&gt;In Silico&lt;/i&gt; and &lt;i&gt;In Vitro&lt;/i&gt; of Novel Trypanosomicidal Drug-like Compounds

Atom-based bilinear indices and linear discriminant analysis are used to discover novel trypanosomicidal compounds. The obtained linear discriminant analysis-based quantitative structure–activity relationship models, using non-stochastic and stochastic indices, provide accuracies of 89.02% (85.11%) and 89.60% (88.30%) of the chemicals in the training (test) sets, respectively. Later, both models were applied to the virtual screening of 18 in-house synthesized compounds to find new pro-lead antitrypanosomal agents. The in vitro antitrypanosomal activity of this set against epimastigote forms of Trypanosoma cruzi is assayed. Predictions agree with experimental results to a great extent (16/18…

New tyrosinase inhibitors selected by atomic linear indices-based classification models.

In the present report, the use of the atom-based linear indices for finding functions that discriminate between the tyrosinase inhibitor compounds and inactive ones is presented. In this sense, discriminant models were applied and globally good classifications of 93.51% and 92.46% were observed for non-stochastic and stochastic linear indices best models, respectively, in the training set. The external prediction sets had accuracies of 91.67% and 89.44%. In addition, these fitted models were used in the screening of new cycloartane compounds isolated from herbal plants. A good behavior is shown between the theoretical and experimental results. These results provide a tool that can be used i…

Classification of stilbenoid compounds by entropy of artificial intelligence

A set of 66 stilbenoid compounds is classified into a system of periodic properties by using a procedure based on artificial intelligence, information entropy theory. Eight characteristics in hierarchical order are used to classify structurally the stilbenoids. The former five features mark the group or column while the latter three are used to indicate the row or period in the table of periodic classification. Those stilbenoids in the same group are suggested to present similar properties. Furthermore, compounds also in the same period will show maximum resemblance. In this report, the stilbenoids in the table are related to experimental data of bioactivity and antioxidant properties avail…

Dry selection and wet evaluation for the rational discovery of new anthelmintics

Helminths infections remain a major problem in medical and public health. In this report, atom-based 2D bilinear indices, a TOMOCOMD-CARDD (QuBiLs-MAS module) molecular descriptor family and linear discriminant analysis (LDA) were used to find models that differentiate among anthelmintic and non-anthelmintic compounds. Two classification models obtained by using non-stochastic and stochastic 2D bilinear indices, classified correctly 86.64% and 84.66%, respectively, in the training set. Equation 1(2) correctly classified 141(135) out of 165 [85.45%(81.82%)] compounds in external validation set. Another LDA models were performed in order to get the most likely mechanism of action of anthelmin…

Cluster Origin of Solvation Features of C-Nanostructures in Organic Solvents

The existence of fullerenes, Single-Wall Carbon Nanocones (SWNCs), especially Nanohorns (SWNHs), Single-Wall Carbon Nanotube (SWNT) (CNT) (NT), NT-Fullerene Bud (NT-BUD), Nanographene (GR) and GR-Fullerene Bud (GR-BUD) in cluster form is discussed in organic solvents. Theories are developed based on columnlet, bundlet and droplet models describing size-distribution functions. The phenomena present a unified explanation in the columnlet model in which free energy of cluster-involved GR comes from its volume, proportional to number of molecules n in cluster. Columnlet model enables describing distribution function of GR stacks by size. From geometrical considerations, columnlet (GR/GR-BUD), b…

&lt;strong&gt;Artemisinin: Tentative Mechanism of Action and Resistance&lt;/strong&gt;

The sesquiterpene lactones constitute a large class of secondary plant metabolites, which carry a‑methylene‑g‑lactone groups as common structural element and display a number of bioactivities. Every year, 1–2 million people living in the tropics and subtropics die of malaria. Lactone artemisinin is the most effective treatment vs. malaria, the most infectious disease in the world today. Artemisinins are derived from extracts of sweet wormwood (Artemisia annua) and are well established for the treatment of malaria, e.g., highly drug-resistant strains. They resulted in one of the most significant advances in the treatment of malaria since the discovery and first use of quinine over 300 years …

Nature of O2, CO, and CN binding to hemoprotein models

Parametrization of a molecular-mechanics program to include terms specific for five- and six-coordinate transition metal complexes results in computer-simulated structures of hemo complexes. The principal new feature peculiar to five- and six-coordination is a term that measures the effect of electron-pair repulsion modified by the ligand electronegativity and takes into account the different structural possibilities. The work consists in the modification of program molecular mechanics for penta and hexacoordination. The model system takes into account the structural differences of the fixing center in the hemoglobin subunits. The customary proximal histidine is added. The macrocycle hemo I…

Interaction of polyelectrolytes with oppositely charged micelles studied by fluorescence and liquid chromatography

It is studied by spectrofluorimetry the association of ionized cationic micelles (cetyltrimethylammonium bromide, CTAB) with oppositely charged polyelectrolyte [sodium poly(styrenesulfonate), PSSNa]. CTAB provokes a change in the fluorescence intensity emitted by PSSNa. The investigated surfactants form micelle-like aggregates before critical micellar concentration (CMC). Two approaches (binding and partition equilibrium) are used to obtain the association constant, KA, number of CTAB molecules in a binding site, N, and apparent partition coefficient, Γ. Analysis of the parameters as a function of polymer concentration and ionic strength μ is performed. The effect of μ shows an enhancement …

Generalized Molecular Descriptors Derived From Event-Based Discrete Derivative.

In the present study, a generalized approach for molecular structure characterization is introduced, based on the relation frequency matrix (F) representation of the molecular graph and the subsequent calculation of the corresponding discrete derivative (finite difference) over a pair of elements (atoms). In earlier publications (22- 24), an unique event, named connected subgraphs, (based on the Kier-Hall's subgraphs) was systematically employed for the computation of the matrix F. The present report is a generalization of this notion, in which eleven additional events are introduced, classified in three categories, namely, topological (terminal paths, vertex path incidence, quantum subgrap…

Discovery of novel trichomonacidals using LDA-driven QSAR models and bond-based bilinear indices as molecular descriptors

Few years ago, the World Health Organization estimated the number of adults with trichomoniasis at 170 million worldwide, more than the combined numbers for gonorrhea, syphilis, and chlamydia. To combat this sexually transmitted disease, Metronidazole (MTZ) has emerged, since 1959, as a powerful drug for the systematic treatment of infected patients. However, increasing resistance to MTZ, adverse effects associated to high-dose MTZ therapies and very expensive conventional technologies related to the development of new trichomonacidals necessitate novel computational methods that shorten the drug discovery pipeline. Therefore, bond-based bilinear indices, new 2-D bond-based TOMOCOMD-CARDD M…

Electrically Conductive Phthalocyanine Assemblies. Structural and Non-Integer Oxidation Number Considerations

Aggregation is a well-known phenomenon in phthalocyanine chemistry. Interactions can occur between adjacent phthalocyanine rings, both in organic and aqueous phases, resulting in coupling between the electronic states of two, or more, phthalocyanine units [1].

Torsional effects on the molecular polarizabilities of the benzothiazole (A)-benzobisthiazole (B) oligomer A-B13-A

Abstract We outline a method for the calculation of multipole moments and molecular dipole-dipole ( ), dipole-quadrupole ( ), and quadrupole-quadrupole ( ) polarizabilities, which we have successfully applied to benzothiazole (A)-benzobisthiazole (B) oligomer A-B13-A. Three model rotational isomers have been characterized: (1) the fully planar (000) rotational isomer; (2) a conformation with each unit rotated 10° in the alternate direction (+−+), and (3) a rotational isomer with each unit rotated 10° in the same direction (+++). The dipole moment, μ , is smaller for isomers 000 and +−+ than for isomer +++. The calculation of , , and has been performed by use of the interacting induced dipol…

Reflections on the Nature of the Periodic Table of the Elements: Implications in Chemical Education

The periodic table of the elements (PTE) results essential to understand our nature and place in the whole of beings. The same happens with our food, drugs, materials, etc. A series of questions were asked to introduce PTE and provide answers. The ideas in PTE should be valued by the number of questions that they generate. The PTE was related to electron configurations. The emergence of elements (nucleosynthesis) in physics was explained. The PTE results essential to understand our nature and place in the whole of beings. The same happens with our food, drugs, materials, etc. Schwarz and Rich asked a series of questions (Qs) to introduce PTE and provided answers. The ideas on PTE should be …

Polarization Force Fields for Peptides Implemented in ECEPP2 and MM2

Abstract The empirical conformational energy program for peptides (ECEPP2) and molecular mechanics (MM2) have been used for the simulation of the For-Gly-NH2 backbone. I propose two different methods for the calculation of the polarization energy term: the polarization procedure by non-interacting induced dipoles (NID) which assumes scalar isotropic point polarizabilities and the polarization scheme by interacting induced dipoles (ID) which calculates tensor effective anisotropic point polarizabilities (method of Applequist). I present a comparative study of ECEPP2 and MM2 + polarization. I discuss molecular mechanics results including the total energy differences, partitional analyses of t…

QSAR Modeling ANTI-HIV-1 Activities by Optimization of Correlation Weights of Local Graph Invariants

Results of using descriptors calculated with the correlation weights (CWs) of local graph invariants for modeling of anti-HIV-1 potencies of two groups of reverse transcriptase (RT) inhibitors are reported. Presence of different chemical elements in molecular structure of the inhibitors and the presence of Morgan extended connectivity values of zeroth-, first- and second order have been examined as local graph invariants in the labeled hydrogen-filled graphs. By Monte Carlo method optimization procedure, values of the CWs which produce as large values as possible of correlation coefficient between the numerical data on the anti-HIV-1 potencies and values of the descriptors on the training s…

Estimation of ADME Properties in Drug Discovery: Predicting Caco-2 Cell Permeability Using Atom-Based Stochastic and Non-stochastic Linear Indices

The in vitro determination of the permeability through cultured Caco-2 cells is the most often-used in vitro model for drug absorption. In this report, we use the largest data set of measured P(Caco-2), consisting of 157 structurally diverse compounds. Linear discriminant analysis (LDA) was used to obtain quantitative models that discriminate higher absorption compounds from those with moderate-poorer absorption. The best LDA model has an accuracy of 90.58% and 84.21% for training and test set. The percentage of good correlation, in the virtual screening of 241 drugs with the reported values of the percentage of human intestinal absorption (HIA), was greater than 81%. In addition, multiple …

Atom-Based 2D Quadratic Indices in Drug Discovery of Novel Tyrosinase Inhibitors: Results ofIn Silico Studies Supported by Experimental Results

Herein we present results of QSAR studies of tyrosinase inhibitors employing one of the atom-based TOMOCOMD-CARDD (acronym of TOpological MOlecular COMputer Design-Computer Aided “Rational” Drug Design) descriptors, molecular quadratic indices, and Linear Discriminant Analysis (LDA) as pattern recognition method. In this way, a database of 246 organic chemicals, reported as tyrosinase inhibitors having great structural variability, was analyzed and presented as a helpful tool, not only for theoretical chemists but also for other researchers in this area. In total, 12 LDA-based QSAR models were obtained, the first six with the non-stochastic total and local quadratic indices and the six rema…

Structure-Activity Relationships of Cytotoxic Lactones as Inhibitors and Mechanisms of Action.

Background: Some lactones prevent protein Myb-dependent gene expression. Objective: The object is to calculate inhibitors of Myb-brought genetic manifestation. Methods: Linear quantitative structure–potency relations result expanded, among sesquiterpene lactones of a variety of macrocycles (pseudoguaianolides, guaianolides, eudesmanolides and germacranolides), to establish which part of the molecule constitutes their pharmacophore, and predict their inhibitory potency on Myb-reliant genetic manifestation, which may result helpful as leads for antileukaemic therapies with a new mechanism of action. Results: Several count indices are connected with structure–activity. The α-methylene-γ-lacto…

Bundlet Model for Single-Wall Carbon Nanotubes, Nanocones and Nanohorns

This paper discusses the existence of single-wall carbon nanocones (SWNCs), especially nanohorns (SWNHs), in organic solvents in the form of clusters. A theory is developed based on a bundlet model describing their distribution function by size. Phenomena have a unified explanation in bundlet model in which free energy of an SWNC, involved in a cluster, is combined from two components: a volume one, proportional to number of molecules n in a cluster, and a surface one proportional to n1/2. Bundlet model enables describing distribution function of SWNC clusters by size. From purely geometrical differences, bundlet (SWNCs) and droplet (fullerene) models predict different behaviours. The SWNCs…

QSPR Modeling of Hydrocarbon Dipole Moments by Means of Correlation Weighting of Local Graph Invariants

Hydrocarbon dipole moments are calculated by means of correlation weighting of local graph invariants within the context of QSPR theory. This sort of flexible topological descriptor is used for several parameters: local invariants of k th vertex in the labeled hydrogen filled graph extended connectivity of zero-, first- and second-orders, number of paths of length 2 at k th vertex and valence shell of the k th vertex. The models predict hydrocarbon dipole moments in a quite sensible way. The best model is that one based upon numbers of path length 2 correlation weighting.

Corrigendum to: “Solvent features of cluster single-wall C, BC2N and BN nanotubes, cones and horns” [Microelectron. Eng. 108 (2013) 127–133]

Universal Organic Solvent−Water Partition Coefficient Model

A method that permits a semiquantitative estimate of the partitioning of any solute between any two media is presented. As an example, the organic solvent-water partition coefficients P are calculated. Program GSCAP is written as a version of Pascal's SCAP program. The only needed parameters are the dielectric constant and molecular volume of the organic solvent. The log P results are compared with the Pomona database. The average absolute deviation is 1.48 log units and the standard deviation is 1.66 log units.

Periodic Classification of Local Anaesthetics (Procaine Analogues)

Algorithms for classification are proposed based on criteria (information entropyand its production). The feasibility of replacing a given anaesthetic by similar ones in thecomposition of a complex drug is studied. Some local anaesthetics currently in use areclassified using characteristic chemical properties of different portions of their molecules.Many classification algorithms are based on information entropy. When applying theseprocedures to sets of moderate size, an excessive number of results appear compatible withdata, and this number suffers a combinatorial explosion. However, after the equipartitionconjecture, one has a selection criterion between different variants resulting fromc…

Mucoadhesive Polymer Hyaluronan as Biodegradable Cationic/Zwitterionic-Drug Delivery Vehicle

Mucoadhesive polymers in pharmaceutical formulations release drugs in mucosal areas. They interact and fix to mucus via molecular interpenetration, etc ., which increase drug bioavailability. Polymers physicochemical properties affect formulation mucoadhesion, rheological behaviour and drug absorption. Hyaluronan (HA) is selected as a mucoadhesive and biodegradable polymer. Geometric, topological and fractal analyses are carried out with program TOPO. Reference calculations are performed with algorithm GEPOL. Procedure TOPO underestimates molecular volume by 0.7%. Error results 5% in surface area and derived topological indices. Solvent-accessible surface is undercalculated by 3%: from hexa…

Aqueous coefficient calculations for chemicals and drugs

Aqueous functional group activity coefficients (AQUAFAC) is a group‐contribution method for estimating the aqueous coefficients. We have written a program for the calculation of these coefficients. The solubility S w of alkanes shows variation of 8 orders of magnitude. The comparison with experiment shows that AQUAFAC gives good S w estimations. For 4'‐substituted acetanilides, I‐, Br‐, nitro‐, Cl‐, F‐ and methoxy‐substituents decrease S w, while formyl‐ and amino‐substituents increase S w. For acetaminophen esters, S w decreases from the acetate to the decanoate. The S w of 29 barbiturates shows typical errors of 0.4 log S w units. For the cyclo‐alkane‐l’,5‐spirobarbituric acids, S w decre…

Table of Periodic Properties of Fullerenes Based on Structural Parameters.

The periodic table (PT) of the elements suggests that hydrogen could be the origin of everything else. The construction principle is an evolutionary process that is formally similar to those of Darwin and Oparin. The Kekulé structure count and permanence of the adjacency matrix of fullerenes are related to structural parameters involving the presence of contiguous pentagons p, q and r. Let p be the number of edges common to two pentagons, q the number of vertices common to three pentagons, and r the number of pairs of nonadjacent pentagon edges shared between two other pentagons. Principal component analysis (PCA) of the structural parameters and cluster analysis (CA) of the fullerenes perm…

State of the Art Review and Report of New Tool for Drug Discovery

BACKGROUND There are a great number of tools that can be used in QSAR/QSPR studies; they are implemented in several programs that are reviewed in this report. The usefulness of new tools can be proved through comparison, with previously published approaches. In order to perform the comparison, the most usual is the use of several benchmark datasets such as DRAGON and Sutherland's datasets. METHODS Here, an exploratory study of Atomic Weighted Vectors (AWVs), a new tool useful for drug discovery using different datasets, is presented. In order to evaluate the performance of the new tool, several statistics and QSAR/QSPR experiments are performed. Variability analyses are used to quantify the…

Dragon method for finding novel tyrosinase inhibitors: Biosilico identification and experimental in vitro assays

QSAR (quantitative structure-activity relationship) studies of tyrosinase inhibitors employing Dragon descriptors and linear discriminant analysis (LDA) are presented here. A data set of 653 compounds, 245 with tyrosinase inhibitory activity and 408 having other clinical uses were used. The active data set was processed by k-means cluster analysis in order to design training and prediction series. Seven LDA-based QSAR models were obtained. The discriminant functions applied showed a globally good classification of 99.79% for the best model Class=-96.067+1.988 x 10(2)X0Av +9 1.907 BIC3 + 6.853 CIC1 in the training set. External validation processes to assess the robustness and predictive pow…

Erratum: Nature of O2, CO, and CN binding to hemoprotein models

The original article to which this Erratum refers was published in International Journal of Quantum Chemistry (2004) 99(6)

QSPR prediction of chromatographic retention times of pesticides: Partition and fractal indices

The high-performance liquid-chromatographic retentions of red-wine pesticide residues are modeled by structure-property relationships. The effect of different types of features is analyzed: geometric, lipophilic, etc. The properties are fractal dimensions, partition coefficient, etc., in linear and nonlinear correlation models. Biological plastic evolution is an evolutionary perspective conjugating the effect of acquired characters and relations that emerge among the principles of evolutionary indeterminacy, morphological determination and natural selection. It is applied to design the co-ordination index that is used to characterize pesticide retentions. The parameters used to calculate th…

Cluster Origin of the Solubility of Single-Wall Carbon Nanotubes

The possibility of the existence of single-wall carbon nanotubes (SWNT) in organic solvents, in the form of clusters containing a number of SWNTs, is discussed. A theory is developed based on a bundletmodel for clusters, which enables describing the distribution function of clusters by size. Comparison of the calculated values of solubility with experimental data would permit obtaining energetic parameters characterizing the interaction of an SWNT with its surrounding in a solid phase or solution. Fullerenes and SWNTs are unique objects, whose behavior in many physical situations is characterized by remarkable peculiarities. Peculiarities in solutions show up in that fullerenes and SWNTs re…

Modeling Studies of the Phase Behavior of Monomer/Polymer/Disk Composites

The model developed by Balazs et al. to explain the phase behavior of polymer/clay composites is extended to monomer/polymer/clay composites, obtaining an expression for the free energy of a monomer/polymer/thin-disk mixture. By minimizing the free energy and calculating the chemical potentials of the three system components, phase diagrams for the monomer/disk and monomer/polymer/disk mixtures are contructed. Through the evolution and comparison of these diagrams, the effects of nanodisk size, polymer molecular mass and interaction parameters (temperature) on mixture stability and attained morphology are then studied.

A novel approach to predict aquatic toxicity from molecular structure

The main aim of the study was to develop quantitative structure-activity relationship (QSAR) models for the prediction of aquatic toxicity using atom-based non-stochastic and stochastic linear indices. The used dataset consist of 392 benzene derivatives, separated into training and test sets, for which toxicity data to the ciliate Tetrahymena pyriformis were available. Using multiple linear regression, two statistically significant QSAR models were obtained with non-stochastic (R2=0.791 and s=0.344) and stochastic (R2=0.799 and s=0.343) linear indices. A leave-one-out (LOO) cross-validation procedure was carried out achieving values of q2=0.781 (scv=0.348) and q2=0.786 (scv=0.350), respecti…

In silicoAntibacterial Activity Modeling Based on the TOMOCOMD-CARDD Approach

In the recent times, the race to cope with the increasing multidrug resistance of pathogenic bacteria has lost much of its momentum and health professionals are grasping for solutions to deal with the unprecedented resistance levels. As a result, there is an urgent need for a concerted effort towards the development of new antimicrobial drugs to stay ahead in the fight against the ever adapting bacteria. In the present report, antibacterial classification functions (models) based on the topological molecular computational design-computer aided >rational> drug design (TOMOCOMD-CARDD) atom-based non-stochastic and stochastic bilinear indices are presented. These models were built using the li…

Calculations on solvents and co-solvents of single-wall carbon nanotubes:cyclopyranoses

The (10, 10) single-wall carbon nanotube (SWNT) presents consistency between relatively small solubility, and large partition coefficients and kinetic stability. The solubility of SWNTs is investigated in a variety of solvents, finding a class of non-hydrogen-bonding Lewis bases that provides good solubility. The organic solvent–water partition and hydrophobic moment of lysozyme show that the main contribution to the water-accessible surface area of helices is the hydrophobic term, while the hydrophilic part dominates in the sheet, which is related to the 1-octanol–, cyclohexane– and chloroform–water partition coefficients Po−ch−cf of helices, which are greater than those of the sheet. The …

Theoretical characterization of iron and manganese porphyrins for catalyzed saturated alkane hydroxylations

Abstract The theoretical characterization of porphin (H2Por), iron and manganese porphyrins MIII(Por) and their chlorine derivatives MIII(Por)Cl has been carried out. This work represents a first step for modelling catalyzed saturated alkane hydroxylations. The chlorine atom is responsible for the existence of a dipole moment of 1.2–2.0 D in the MIII(Por)Cl molecules and for a negative value of the mean quadrupole moment (−16–(−14)DA). The charge of the metal atom (1.8–2.2 e) is rather varied (to 2.1–2.6 e) and the effective polarizability (2.8–2.9 A3) is increased (to 3.5–3.6 A3) by the addition of the chlorine atom. Starting from the porphin molecule, the presence of the metal atom decrea…

A Comparative Study of Nonlinear Machine Learning for the "In Silico" Depiction of Tyrosinase Inhibitory Activity from Molecular Structure.

In the preset report, for the first time, support vector machine (SVM), artificial neural network (ANN), Baye- sian networks (BNs), k-nearest neighbor (k-NN) are applied and compared on two "in-house" datasets to describe the tyrosinase inhibitory activity from the molecular structure. The data set Data I is used for the identification of tyrosi- nase inhibitors (TIs) including 701 active and 728 inactive compounds. Data II consists of active chemicals for potency estimation of TIs. The 2D TOMOCOMD-CARDD atom-based quadratic indices are used as molecular descriptors. The de- rived models show rather encouraging results with the areas under the Receiver Operating Characteristic (AURC) curve …

Improvement of charge-transfer indices for multifunctional amino acids: Application to lysozyme

Valence topological Charge-Transfer (CT) indices are applied to the calculation of pH at the isoelectric point (pI). The model is generalized for molecules with heteroatoms. The ability of the indices for the description of molecular charge distribution is established by comparing them with the pI of 21 amino acids. Linear correlation models are obtained. The CT indices improve multivariable regression equations for pI. The variance decreases by 95%. No superimposition of the corresponding G(k)-J(k) and G(k)(V)-J(k)(V) pairs is observed in most fits, which diminishes the risk of collinearity. The inclusion of heteroatoms in pi-electron system is beneficial for the description of pI, the bec…

Atom-based Stochastic and non-Stochastic 3D-Chiral Bilinear Indices and their Applications to Central Chirality Codification

Abstract Non-stochastic and stochastic 2D bilinear indices have been generalized to codify chemical structure information for chiral drugs, making use of a trigonometric 3D-chirality correction factor. In order to evaluate the effectiveness of this novel approach in drug design we have modeled the angiotensin-converting enzyme inhibitory activity of perindoprilate's σ-stereoisomers combinatorial library. Two linear discriminant analysis models, using non-stochastic and stochastic linear indices, were obtained. The models had shown an accuracy of 95.65% for the training set and 100% for the external prediction set. Next the prediction of the σ-receptor antagonists of chiral 3-(3-hydroxypheny…

QuBiLs-MAS method in early drug discovery and rational drug identification of antifungal agents

The QuBiLs-MAS approach is used for the in silico modelling of the antifungal activity of organic molecules. To this effect, non-stochastic (NS) and simple-stochastic (SS) atom-based quadratic indices are used to codify chemical information for a comprehensive dataset of 2478 compounds having a great structural variability, with 1087 of them being antifungal agents, covering the broadest antifungal mechanisms of action known so far. The NS and SS index-based antifungal activity classification models obtained using linear discriminant analysis (LDA) yield correct classification percentages of 90.73% and 92.47%, respectively, for the training set. Additionally, these models are able to correc…

&lt;strong&gt;New tool useful for drug discovery validated through benchmark datasets&lt;/strong&gt;

Atomic Weighted Vectors (AWVs) are vectors that contain the codified information of molecular structures, which can apply to a set of Aggregation Operators (AOs) to calculate total and local molecular descriptors (MDs). This article presents an exploratory study of a new tool useful for drug discovery using different datasets, such as DRAGON and Sutherland’s datasets, as well as their comparison with other well-known approaches. In order to evaluate the performance of the tool, several statistics and QSAR/QSPR experiments were performed. Variability analyses are used to quantify the information content of the AWVs obtained from the tool, by the way of an information theory-based algorithm. …

Vectorized ‘‘TOPO’’ Program for the Theoretical Simulation of Molecular Shape

The TOPO program for theoretical simulation of molecular shape is presented here. Molecular shape is characterized by a set of electrostatic and geometrical descriptors and topological indices including the fractal dimension of the accessible surface. An atom-atom analysis of all descriptors has been implemented. The program has been adapted for the realization of high-performance computing. Results are reported for porphine and phthalocyanine molecules.

Molecular Clustering of Phenylurea Herbicides: Comparison with Sulphonylureas, Pesticides and Persistent Organic Pollutants

Chromatographic retention times of phenylurea herbicides are modelled by structure–property relationships. Properties are hydration free energy and dipole. Bioplastic evolution is an evolutionary perspective conjugating the effect of acquired characters and relations that emerge among evolutionary indeterminacy, morphological determination and natural selection principles. Classification algorithms are proposed based on information entropy and production. Phenylureas are classified by Cl2, O2 and N2 presence; their different behaviour depends on the number of Cl atoms. When applying procedures to moderate-sized sets, excessive results appear compatible with data and suffer a combinatorial e…

Universal model for the calculation of all organic solvent–water partition coefficients

Abstract We present the basis for building a universal organic solvation model to calculate solubility in any organic solvent and in water, as well as the organic solvent–water partition coefficient ( P ). Log P values are of the same order of magnitude as reference calculations but for a few cases which are discussed. Normalized log P contributions are sensitive to the rest of the atoms. When comparing porphin with phthalocyanine, the latter results in an amphipathic molecule. For C 70 , the contribution of a–e carbons to log P correlates with the distances from the nearest pentagon. The method has been also applied to benzobisthiazole oligomers and phenyl alcohols.

Effect of size and deformation on polarizabilities of carbon nanotubes from atomic increments

The interacting induced-dipole polarization model implemented in program POLAR is used for the calculation of the polarizability α. The method is tested with single-wall carbon nanotubes (SWNTs) as a function of radius and elliptical deformation. This work gives a partial success with the application of POLAR when compared with reference calculations performed with program PAPID. α follows a simple law. PAPID differentiates more effectively than POLAR among SWNTs with increasing radial deformation, a can be modified reversibly by external radial deformation. Different effective αeff are calculated for the atoms at the highest and lowest curvature sites. The difference between POLAR and PAPI…

Bond-based 3D-chiral linear indices: Theory and QSAR applications to central chirality codification

The recently introduced non-stochastic and stochastic bond-based linear indices are been generalized to codify chemical structure information for chiral drugs, making use of a trigonometric 3D-chirality correction factor. These improved modified descriptors are applied to several well-known data sets to validate each one of them. Particularly, Cramer's steroid data set has become a benchmark for the assessment of novel quantitative structure activity relationship methods. This data set has been used by several researchers using 3D-QSAR approaches such as Comparative Molecular Field Analysis, Molecular Quantum Similarity Measures, Comparative Molecular Moment Analysis, E-state, Mapping Prope…

Classification of Complex Molecules

Algorithms for classification and taxonomy based on criteria, e.g., information entropy and its production are proposed. In molecular classification, the feasibility of replacing a given molecule (e.g, anaesthetic) by similar ones in the composition of a complex drug is studied. Some local anaesthetics currently in use are classified using characteristic chemical properties of different portions of their molecules. In taxonomy, the detailed comparison of the sequences (primary structures) of biomolecules, proteins or nucleic acids, allows the reconstruction of a molecular phylogenetic tree for some species, e.g. the 1918 influenza virus. The method is applied to the classifications of: (1) …

Resonance in Interacting Induced-Dipole Polarizing Force Fields: Application to Force-Field Derivatives

The Silberstein model of the molecular polarizability of diatomic molecules, generalized by Applequist et al. for polyatomic molecules, is analyzed. The atoms are regarded as isotropically polarizable points located at their nuclei, interacting via the fields of their induced dipoles. The use of additive values for atom polarizabilities gives poor results, in some cases leading to artificial predictions of absorption bands. The molecular polarizability of methane and its derivative are computed. The agreement with experimental mean molecular polarizabilities is within 1–5%. A hypothesis is indispensable for a suitable representation of polarizability derivative.

Valence Topological Charge-Transfer Indices for Reflecting Polarity: Correction for Heteromolecules

Valence topological charge-transfer (CT) indices are applied to the calculation of dipole moments mu. The mu calculated by algebraic and vector semisums of the CT indices are defined. The model is generalized for molecules with heteroatoms and corrected for sp(3)-heteromolecules. The ability of the indices for the description of the molecular charge distribution is established by comparing them with mu of the valence-isoelectronic series of cyclopentadiene, benzene and styrene. Two CT indices, mu(vec) (vector semisum of vertex-pair mu) and mu(vec)V (valence mu(vec)) are proposed. The mu(vec) behaviour is intermediate between mu(vec) and mu(experiment). The correction is produced in the corr…

Molecular polarizability of Scn, Cn and endohedral Scn@Cm clusters

The interacting induced dipoles polarization model implemented in the program POLAR is used for the calculation of the molecular dipole-dipole polarizability . The method is tested with Sc1-Sc7, Sc12, Sc17, Sc74, C, C12, C60, C70, C82-fullerene, Sc@C60, Sc@C82, Sc2@C82, Sc3@C82, C1-C6, C10, C13, C16, C19, C22, C24, C42, C54, C84 and C96-graphite clusters. The polarizability is an important quantity for the identification of clusters with different numbers of atoms and even for the separation of isomers. The results for the polarizability are of the same order of magnitude as reference calculations performed with another program based on the same formulation. The bulk limit for the polarizab…

Binding of water-soluble, globular proteins to anionic model membranes

Abstract The role of electrostatics is studied in the adsorption of proteins to negatively charged (phosphatidylcholine/phosphatidylglycerol, PC/PG) and neutral (PC) small unilamellar vesicles (SUVs). For model proteins the interaction is monitored vs . pH at low ionic strength. The adsorption behaviour of lysozyme, myoglobin and albumin (isoelectronic point, p I 5–11) is investigated in SUVs, along with changes of the fluorescence emission spectra of the charged proteins, via their adsorption on SUVs. Significant adsorption of the proteins to negatively charged SUVs is found only at pH values, where the number of positive charge moieties exceeds the number of negative charge moieties on th…

Molecular polarizability of semiconductor clusters and nanostructures

Abstract The interacting-induced-dipoles polarization model implemented in program PAPID is used for the calculation of the molecular dipole–dipole polarizability α . The method is tested with Si n , Ge n and GanAsm small clusters. On varying the number of atoms, the clusters show numbers indicative of particularly polarizable structures. The results for the polarizability are in agreement with reference calculations from Chelikowsky. The bulk limit for the polarizability is estimated from the Clausius–Mossotti relationship. The polarizability trend for these clusters as a function of size is different from what one might have expected. The clusters are all more polarizable than what one mi…

Classification of Congeneric and QSAR of Homologous Antileukemic S–Alkylcysteine Ketones

Based on a set of six vector properties, the partial correlation diagram is calculated for a set of 28 S-alkylcysteine diazomethyl- and chloromethyl-ketone derivatives. Those with the greatest antileukemic activity in the same class correspond to high partial correlations. A periodic classification is performed based on information entropy. The first four characteristics denote the group, and the last two indicate the period. Compounds in the same period and, especially, group present similar properties. The most active substances are situated at the bottom right. Nine classes are distinguished. The principal component analysis of the homologous compounds shows five subclasses included in t…

AMYR 2: A new version of a computer program for pair potential calculation of molecular associations

AMYR is a computer program for the calculation of molecular associations using Fraga's pairwise atom-atom potential. The interaction energy is evaluated through a 1R expansion. The electrostatic energy is calculated through either the one-centre-per atom or the three-centres-per atom model by Hunter and Sanders. A pairwise dispersion energy term is included in the potential and corrected by a damping function. The program carries out energy minimizations through variable metric methods. The new version allows for the stationary point analysis of the intermolecular potential by means of the Hessian eigenvalues. Although using low-gradient thresholds optimization procedures to avoid many stat…

Machine learning-based models to predict modes of toxic action of phenols to Tetrahymena pyriformis.

The phenols are structurally heterogeneous pollutants and they present a variety of modes of toxic action (MOA), including polar narcotics, weak acid respiratory uncouplers, pro-electrophiles, and soft electrophiles. Because it is often difficult to determine correctly the mechanism of action of a compound, quantitative structure-activity relationship (QSAR) methods, which have proved their interest in toxicity prediction, can be used. In this work, several QSAR models for the prediction of MOA of 221 phenols to the ciliated protozoan Tetrahymena pyriformis, using Chemistry Development Kit descriptors, are reported. Four machine learning techniques (ML), k-nearest neighbours, support vector…

Bond-Based 2D Quadratic Fingerprints in QSAR Studies: Virtual and In vitro Tyrosinase Inhibitory Activity Elucidation

In this report, we show the results of quantitative structure–activity relationship (QSAR) studies of tyrosinase inhibitory activity, by using the bond-based quadratic indices as molecular descriptors (MDs) and linear discriminant analysis (LDA), to generate discriminant functions to predict the anti-tyrosinase activity. The best two models [Eqs (6) and (12)] out of the total 12 QSAR models developed here show accuracies of 93.51% and 91.21%, as well as high Matthews correlation coefficients (C) of 0.86 and 0.82, respectively, in the training set. The validation external series depicts values of 90.00% and 89.44% for these best two equations (6) and (12), respectively. Afterwards, a second …

Calculation of organic solvent–water partition coefficients of iron–sulfur protein models

Abstract A method is presented that permits semiquantitative estimation of the partitioning of many solutes between many pairs of media. As an example, the organic solvent–water partition coefficients P are calculated. The only needed parameters are the dielectric constant and molecular volume of the organic solvent. Fe 4 S 4 Cys n models of high-potential FeS proteins are studied. The Gibbs free energies of solvation and partition coefficients for Fe 4 S 4 Cys n are calculated. The organic solvent–water partition coefficients for 1-octanol P o , cyclohexane P ch and chloroform P cf decrease 4.41, 6.22 and 4.60 log units per cysteine (Cys) ligand, respectively. P o results are compared with…

Atom, atom-type and total molecular linear indices as a promising approach for bioorganic and medicinal chemistry: theoretical and experimental assessment of a novel method for virtual screening and rational design of new lead anthelmintic.

Abstract Helminth infections are a medical problem in the world nowadays. In this paper a novel atom-level chemical descriptor has been applied to estimate the anthelmintic activity. Total and local linear indices and linear discriminant analysis were used to obtain a quantitative model that discriminates between anthelmintic and non-anthelmintic drug-like compounds. The discriminant model has an accuracy of 90.11% in the training set, with a high Matthews’ correlation coefficient (MCC = 0.80). To assess the robustness and predictive power of the obtained model, internal (leave-n-out) and external validation process was performed. The QSAR model correctly classified 88.55% of compounds in t…

AMYR 2: A new version of a computer program for pair potential calculation of molecular associations

Abstract AMYR is a computer program for the calculation of molecular associations using Fraga's pairwise atom - atom potential. The interaction energy is evaluated through a 1/R expansion. The electrostatic energy is calculated through either the one-centre-per atom or the three-centres-per atom model by Hunter and Sanders. A pairwise dispersion energy term is included in the potential and corrected by a damping function. The program carries out energy minimizations through variable metric methods. Th... Title of program: AMYR 2 Catalogue Id: ADIW_v1_0 Nature of problem The program determines the optimum separation and relative orientation of two interacting molecular systems through a mini…

Pair potential calculation of molecular associations: a vectorized version

Abstract The program AMYRVF is a vectorized and largely modified version of a previous program called AMYR for calculating molecular associations by means of Fraga's pair-wise atom-atom potential. Three new minimization procedures have been implemented as well as other improvements such as the inclusion of new pair-wise dispersion energy terms with damping functions, and the calculation of topological indices. Benchmark tests have been carried out on an IBM 3090 150E VF; the timings for the new vector... Title of program: AMYRVF Catalogue Id: ACBG_v1_0 Nature of problem This program determines the optimum separation and relative orientation of two interacting molecular systems through a min…

In silico Antibacterial Activity Modeling Based on the TOMOCOMD-CARDD Approach

In the recent times, the race to cope with the increasing multidrug resistance of pathogenic bacteria has lost much of its momentum and health professionals are grasping for solutions to deal with the unprecedented resistance levels. As a result, there is an urgent need for a concerted effort towards the development of new antimicrobial drugs to stay ahead in the fight against the ever adapting bacteria. In the present report, antibacterial classification functions (models) based on the topological molecular computational design-computer aided ‘‘rational’’ drug design (TOMOCOMD-CARDD) atom-based non-stochastic and stochastic bilinear indices are presented. These models were built using the …