Search results for: QSAR

Authors: Madhusudan Purohit, Stephen Philip, Bharathkumar Inturi

Abstract:

In this paper we report the quantitative structure activity relationship of novel bis-triazole derivatives for predicting the activity profile. The full model encompassed a dataset of 46 Bis- triazoles. Tripos Sybyl X 2.0 program was used to conduct CoMSIA QSAR modeling. The Partial Least-Squares (PLS) analysis method was used to conduct statistical analysis and to derive a QSAR model based on the field values of CoMSIA descriptor. The compounds were divided into test and training set. The compounds were evaluated by various CoMSIA parameters to predict the best QSAR model. An optimum numbers of components were first determined separately by cross-validation regression for CoMSIA model, which were then applied in the final analysis. A series of parameters were used for the study and the best fit model was obtained using donor, partition coefficient and steric parameters. The CoMSIA models demonstrated good statistical results with regression coefficient (r²) and the cross-validated coefficient (q²) of 0.575 and 0.830 respectively. The standard error for the predicted model was 0.16322. In the CoMSIA model, the steric descriptors make a marginally larger contribution than the electrostatic descriptors. The finding that the steric descriptor is the largest contributor for the CoMSIA QSAR models is consistent with the observation that more than half of the binding site area is occupied by steric regions.

Keywords: 3D QSAR, CoMSIA, Triazoles.

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Authors: Luminita Dumitriu, Cristina Segal, Marian Craciun, Adina Cocu, Lucian P. Georgescu

Abstract:

There are several approaches in trying to solve the Quantitative 1Structure-Activity Relationship (QSAR) problem. These approaches are based either on statistical methods or on predictive data mining. Among the statistical methods, one should consider regression analysis, pattern recognition (such as cluster analysis, factor analysis and principal components analysis) or partial least squares. Predictive data mining techniques use either neural networks, or genetic programming, or neuro-fuzzy knowledge. These approaches have a low explanatory capability or non at all. This paper attempts to establish a new approach in solving QSAR problems using descriptive data mining. This way, the relationship between the chemical properties and the activity of a substance would be comprehensibly modeled.

Keywords: association rules, classification, data mining, Quantitative Structure - Activity Relationship.

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Authors: Irene Luque Ruiz, Manuel Urbano Cuadrado, Miguel Ángel Gómez-Nieto

Abstract:

In this paper we study different similarity based approaches for the development of QSAR model devoted to the prediction of activity of antiobesity drugs. Classical similarity approaches are compared regarding to dissimilarity models based on the consideration of the calculation of Euclidean distances between the nonisomorphic fragments extracted in the matching process. Combining the classical similarity and dissimilarity approaches into a new similarity measure, the Approximate Similarity was also studied, and better results were obtained. The application of the proposed method to the development of quantitative structure-activity relationships (QSAR) has provided reliable tools for predicting of inhibitory activity of drugs. Acceptable results were obtained for the models presented here.

Keywords: Graph similarity, Nonisomorphic dissimilarity, Approximate similarity, Drugs activity prediction.

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Authors: Ponco Iswanto, Mochammad Chasani, Muhammad Hanafi, Iqmal Tahir, Eva Vaulina YD, Harjono, Lestari Solikhati, Winkanda S. Putra, Yayuk Yuliantini

Abstract:

Quantitative Structure-Activity Relationship (QSAR) approach for discovering novel more active Calanone derivative as anti-leukemia compound has been conducted. There are 6 experimental activities of Calanone compounds against leukemia cell L1210 that are used as material of the research. Calculation of theoretical predictors (independent variables) was performed by AM1 semiempirical method. The QSAR equation is determined by Principle Component Regression (PCR) analysis, with Log IC50 as dependent variable and the independent variables are atomic net charges, dipole moment (μ), and coefficient partition of noctanol/ water (Log P). Three novel Calanone derivatives that obtained by this research have higher activity against leukemia cell L1210 than pure Calanone.

Keywords: AM1 semiempirical calculation, Calanone, Principle Component Regression, QSAR approach.

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Authors: Suman Bala, Sunil Kamboj, Vipin Saini

Abstract:

Quantitative Structure Activity Relationship (QSAR) analysis has been developed to relate antifungal activity of novel substituted 1,3,4-oxadiazole against Candida albicans and Aspergillus niger using computer assisted multiple regression analysis. The study has shown the better relationship between antifungal activities with respect to various descriptors established by multiple regression analysis. The analysis has shown statistically significant correlation with R² values 0.932 and 0.782 against Candida albicans and Aspergillus niger respectively. These derivatives were further subjected to molecular docking studies to investigate the interactions between the target compounds and amino acid residues present in the active site of glucosamine-6-phosphate synthase. All the synthesized compounds have better docking score as compared to standard fluconazole. Our results could be used for the further design as well as development of optimal and potential antifungal agents.

Keywords: 1, 3, 4-Oxadiazole, QSAR, Multiple linear regression, Docking, Glucosamine-6-Phosphate Synthase.

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Authors: Kozak K, M. Kozak, K. Stapor

Abstract:

The k-nearest neighbors (knn) is a simple but effective method of classification. In this paper we present an extended version of this technique for chemical compounds used in High Throughput Screening, where the distances of the nearest neighbors can be taken into account. Our algorithm uses kernel weight functions as guidance for the process of defining activity in screening data. Proposed kernel weight function aims to combine properties of graphical structure and molecule descriptors of screening compounds. We apply the modified knn method on several experimental data from biological screens. The experimental results confirm the effectiveness of the proposed method.

Keywords: biological screening, kernel methods, KNN, QSAR

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Authors: Irene Luque Ruiz, Manuel Urbano Cuadrado, Miguel Ángel Gómez-Nieto

Abstract:

New graph similarity methods have been proposed in this work with the aim to refining the chemical information extracted from molecules matching. For this purpose, data fusion of the isomorphic and nonisomorphic subgraphs into a new similarity measure, the Approximate Similarity, was carried out by several approaches. The application of the proposed method to the development of quantitative structure-activity relationships (QSAR) has provided reliable tools for predicting several pharmacological parameters: binding of steroids to the globulin-corticosteroid receptor, the activity of benzodiazepine receptor compounds, and the blood brain barrier permeability. Acceptable results were obtained for the models presented here.

Keywords: Graph similarity, Nonisomorphic dissimilarity, Approximate similarity, Drug activity prediction.

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Authors: Mária Stachová, Lukáš Sobíšek

Abstract:

Data mining incorporates a group of statistical methods used to analyze a set of information, or a data set. It operates with models and algorithms, which are powerful tools with the great potential. They can help people to understand the patterns in certain chunk of information so it is obvious that the data mining tools have a wide area of applications. For example in the theoretical chemistry data mining tools can be used to predict moleculeproperties or improve computer-assisted drug design. Classification analysis is one of the major data mining methodologies. The aim of thecontribution is to create a classification model, which would be able to deal with a huge data set with high accuracy. For this purpose logistic regression, Bayesian logistic regression and random forest models were built using R software. TheBayesian logistic regression in Latent GOLD software was created as well. These classification methods belong to supervised learning methods. It was necessary to reduce data matrix dimension before construct models and thus the factor analysis (FA) was used. Those models were applied to predict the biological activity of molecules, potential new drug candidates.

Keywords: data mining, classification, drug design, QSAR

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