Search results for "Quantitative"
showing 10 items of 2409 documents
On the contribution of molecular topology to drug design and discovery.
2010
Abstract The role of molecular topology (MT) in the design and selection of new drugs is discussed. After an overview of the different in silico molecular design current technologies, the QSAR analysis is dealt in detail with particular emphasis in the use of topological indices as molecular descriptors. The results of the application of MT in drug design and discovery are described and finally a possible explanation is given about some of the key reasons explaining it's the extraordinary performance.
Advances in the molecular modeling and quantitative structure–activity relationship-based design for antihistamines
2013
Nowadays the use of antihistamines (AH) is increasing steadily. These drugs are able to act on a variety of pathological conditions of the organism. A number of computer-aided (in silico) approaches have been developed to discover and develop novel AH drugs. Among these methods stand the ones based on drug-receptor docking, thermodynamics, as well as the quantitative structure-activity relationships (QSAR).This review collates the most recent advances in the use of computer approaches for the search and characterization of novel AH drugs. Within the QSAR methods, particular attention will be paid to those based on molecular topology (MT) because of their demonstrated efficacy in discovering…
Computational Methods in Developing Quantitative Structure-Activity Relationships (QSAR): A Review
2006
Virtual filtering and screening of combinatorial libraries have recently gained attention as methods complementing the high-throughput screening and combinatorial chemistry. These chemoinformatic techniques rely heavily on quantitative structure-activity relationship (QSAR) analysis, a field with established methodology and successful history. In this review, we discuss the computational methods for building QSAR models. We start with outlining their usefulness in high-throughput screening and identifying the general scheme of a QSAR model. Following, we focus on the methodologies in constructing three main components of QSAR model, namely the methods for describing the molecular structure …
Nucleotide's bilinear indices: Novel bio-macromolecular descriptors for bioinformatics studies of nucleic acids. I. Prediction of paromomycin's affin…
2009
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)…
Application of molecular topology to the prediction of the antimalarial activity of a group of uracil-based acyclic and deoxyuridine compounds.
2008
A topological-mathematical model has been arranged to search for new derivatives of deoxyuridine and related compounds acting as antimalarials against Plasmodium falciparum. By using linear discriminant and multilinear regression analysis a model with two functions was capable to predict adequately the IC(50) for each compound of the training and test series. After carrying out a virtual screening based upon such a model, new structures potentially active against P. falciparum are proposed.
5-(3,4-Dimethoxybenzyl)-7-isopropyl-1,3,5-triazepane-2,6-dione acetonitrile solvate refined using a multipolar atom model
2010
International audience; The crystal structure of the title compound, C16H23N3O4·CH3CN, was refined using a multipolar atom model transferred from an experimental electron-density database. The refinement showed some improvement in crystallographic statistical indices compared with the independent atom model. The triazepane ring adopts a twist-boat conformation. In the crystal structure, the molecule forms intermolecular contacts with 14 different neighbours. There are two N-H...O and one C-H...O intermolecular hydrogen bond.
Synthesis, in vitro activity, and three-dimensional quantitative structure-activity relationship of novel hydrazine inhibitors of human vascular adhe…
2010
Vascular adhesion protein-1 (VAP-1) belongs to the semicarbazide-sensitive amine oxidases (SSAOs) that convert amines into aldehydes. SSAOs are distinct from the mammalian monoamine oxidases (MAOs), but their substrate specificities are partly overlapping. VAP-1 has been proposed as a target for anti-inflammatory drug therapy because of its role in leukocyte adhesion to endothelium. Here, we describe the synthesis and in vitro activities of novel series of VAP-1 selective inhibitors. In addition, the molecular dynamics simulations performed for VAP-1 reveal that the movements of Met211, Ser496, and especially Leu469 can enlarge the ligand-binding pocket, allowing larger ligands than those s…
String kernels and high-quality data set for improved prediction of kinked helices in α-helical membrane proteins.
2011
The reasons for distortions from optimal α-helical geometry are widely unknown, but their influences on structural changes of proteins are significant. Hence, their prediction is a crucial problem in structural bioinformatics. For the particular case of kink prediction, we generated a data set of 132 membrane proteins containing 1014 manually labeled helices and examined the environment of kinks. Our sequence analysis confirms the great relevance of proline and reveals disproportionately high occurrences of glycine and serine at kink positions. The structural analysis shows significantly different solvent accessible surface area mean values for kinked and nonkinked helices. More important, …
An in vitro comparative assessment with a series of new triphenyltin(IV) 2-/4-[(E)-2-(aryl)-1-diazenyl]benzoates endowed with anticancer activities: …
2012
Four new triphenyltin(IV) complexes of composition Ph 3SnLH (where LH = 2-/4-[(E)-2-(aryl)-1-diazenyl]benzoate) (1-4) were synthesized and characterized by spectroscopic ( 1H, 13C and 119Sn NMR, IR, 119Sn Mössbauer) techniques in combination with elemental analysis. The 119Sn NMR spectroscopic data indicate a tetrahedral coordination geometry in non-coordinating solvents. The crystal structures of three complexes, Ph 3SnL 1H (1), Ph 3SnL 3H (3), Ph 3SnL 4H (4), were determined. All display an essentially tetrahedral geometry with angles ranging from 93.50(8) to 124.5(2)°; 119Sn Mössbauer spectral data support this assignment. The cytotoxicity studies were performed with complexes 1-4, along…
Protein knot server: detection of knots in protein structures
2007
KNOTS (http://knots.mit.edu) is a web server that detects knots in protein structures. Several protein structures have been reported to contain intricate knots. The physiological role of knots and their effect on folding and evolution is an area of active research. The user submits a PDB id or uploads a 3D protein structure in PDB or mmCIF format. The current implementation of the server uses the Alexander polynomial to detect knots. The results of the analysis that are presented to the user are the location of the knot in the structure, the type of the knot and an interactive visualization of the knot. The results can also be downloaded and viewed offline. The server also maintains a regul…