Search results for "Molecular Descriptor"

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

2010

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…

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

2007

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…

Prediction of potential environmental toxicity of chemicals in <em>Lactuca sativa</em> seed germination using computational tools

2019

The main aim of the study was to develop quantitative structure-activity relationship (QSAR) models for the prediction of phytotoxicity effects of chemical compounds on the Lactuca sativa seeds germination. A database of 73 compounds, assayed against L. sativa and Dragon’s molecular descriptors are used to obtain a QSAR model for the prediction of the phytotoxicity. The model is carried out with QSARINS software and validated according to OECD principles. The best model showed good value for the determination coefficient (R2 = 0.917) and others parameters appropriate for fitting (s = 0.256 and RMSEtr= 0.236). The validation results confirmed that the model has good robustness and stability …

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

2018

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…

THE PURPOSING OF NEW COMPOUNDS OR THE RE-PURPOSING OF OLD DRUGS BY MEANS OF MULTIVARIATE ANATYSIS ON MOLECULAR DESCRIPTORS

2010

Virtual lock-and-key approach: The in silico revival of Fischer model by means of molecular descriptors

2010

Abstract In the last years the application of computational methodologies in the medicinal chemistry fields has found an amazing development. All the efforts were focused on the searching of new leads featuring a close affinity on a specific biological target. Thus, different molecular modeling approaches in simulation of molecular behavior for a specific biological target were employed. In spite of the increasing reliability of computational methodologies, not always the designed lead, once synthesized and screened, are suitable for the chosen biological target. To give another chance to these compounds, this work tries to resume the old concept of Fischer lock-and-key model. The same can …

A Multivariate Analysis of HIV-1 Protease Inhibitors and Resistance Induced by Mutation

2005

This paper describes the use of the multivariate statistical procedure principal component analysis as a tool to explore the inhibitory activity of classes of protease inhibitors (PIs) against HIV-1 viruses (wild type and more-frequent single mutants, V82A, V82F, and I84V) and against protease enzymes. The analysis of correlations between biological activity and molecular descriptors or similarity indexes allowed a reliable classification of the 51 derivatives considered in this study. The best results were obtained in the case of the I84V mutant for which a high number of predictions was achieved. On this basis, this statistical approach is proposed as a reliable method for the prediction …

<strong>New tool useful for drug discovery validated through benchmark datasets</strong>

2018

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. …

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

2008

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…

DRUDIT: Web-based DRUgs DIscovery Tools to design small molecules as modulators of biological targets

2019

Abstract Motivation New in silico tools to predict biological affinities for input structures are presented. The tools are implemented in the DRUDIT (DRUgs DIscovery Tools) web service. The DRUDIT biological finder module is based on molecular descriptors that are calculated by the MOLDESTO (MOLecular DEScriptors TOol) software module developed by the same authors, which is able to calculate more than one thousand molecular descriptors. At this stage, DRUDIT includes 250 biological targets, but new external targets can be added. This feature extends the application scope of DRUDIT to several fields. Moreover, two more functions are implemented: the multi- and on/off-target tasks. These tool…