QSAR study of C allosteric binding site of HCV NS5B polymerase inhibitors by support vector machine

被引：0
作者：
Eslam Pourbasheer
Siavash Riahi
Mohammad Reza Ganjali
Parviz Norouzi
机构：
[1] University of Tehran,Center of Excellence in Electrochemistry, Faculty of Chemistry
[2] University of Tehran,Institute of Petroleum Engineering, Faculty of Engineering
来源：
Molecular Diversity | 2011年 / 15卷
关键词：
QSAR; Support vector machine; Multiple linear regressions; Genetic algorithms; Hepatitis C virus (HCV); Chemometrics;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Multiple linear regressions (MLR) and support vector machine (SVM) were used to develop quantitative structure–activity relationship (QSAR) models of novel Hepatitis C virus (HCV) NS5B polymerase inhibitors. Various kinds of molecular descriptors were calculated to represent the molecular structures of compounds, such as chemical, topological, geometrical, and quantum descriptors. Principal component analysis (PCA) was used to select the training set. A variable selection method utilizing a genetic algorithm (GA) was employed to select from the large pool of calculated descriptors, an optimal subset of descriptors which have significant contribution to the overall inhibitory activity. The models were validated using Leave-One-Out (LOO) and Leave-Group-Out (LGO) crossvalidation, and Y-randomization test. Results demonstrated the SVM model offers powerful prediction capabilities.
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页码：645 / 653
页数：8
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  • [1] Ikegashira K(2006)Discovery of conformationally constrained tetracyclic compounds as potent hepatitis C virus NS5B RNA polymerase inhibitors J Med Chem 49 6950-6953
  • [2] Oka T(2006)Discovery of proline sulfonamides as potent and selective hepatitis C virus NS5b polymerase inhibitors. Evidence for a new NS5b polymerase binding site J Med Chem 49 3052-3055
  • [3] Hirashima S(2004)The hepatitis C virus replicase: insights into RNA-dependent RNA replication and prospects for rational drug design Curr Org Chem 8 223-241
  • [4] Noji S(2008)Novel HCV NS5B polymerase inhibitors derived from 4-(1′,1′-dioxo-1′,4′-dihydro-1′λ6-benzo[1′,2′,4′]thiadiazin-3′-yl)-5-hydroxy-2H-pyridazin-3-ones. Part 1. Exploration of 7′-substitution of benzothiadiazine Bioorg Med Chem Lett 18 1413-1418
  • [5] Yamanaka H(2008)Novel HCV NS5B polymerase inhibitors derived from 4-(1′,1′-dioxo-1′,4′-dihydro-1′ λ6-benzo[1′,2′,4′]thiadiazin-3′-yl)-5-hydroxy-2H-pyridazin-3-ones. Part 2. Variation of the 2- and 6-pyridazinone substituents Bioorg Med Chem Lett 18 1419-1424
  • [6] Hara Y(2008)Novel HCV NS5B polymerase inhibitors derived from 4-(1′,1′-dioxo-1′,4′-dihydro-1 ′ λ6-benzo[1′,2′,4′]thiadiazin −3′-yl)-5-hydroxy-2H-pyridazin-3-ones. Part 3. Further optimization of the 2-, 6-, and 7′-substituents and initial pharmacokinetic assessments Bioorg Med Chem Lett 18 3446-3455
  • [7] Adachi T(2008)Novel HCV NS5B polymerase inhibitors derived from 4-(1′,1′-dioxo-1′,4′-dihydro-1′ λ6-benzo[1′,2′,4′]thiadiazin-3′-yl)-5-hydroxy-2H-pyridazin-3-ones. Part 4. Optimization of DMPK properties Bioorg Med Chem Lett 18 3421-3426
  • [8] Tsuruha J-I(2008)Novel HCV NS5B polymerase inhibitors derived from 4-(1′,1′-dioxo-1′,4′-dihydro-1′ λ6-benzo[1′,2′,4′]thiadiazin-3′-yl)-5-hydroxy-2H-pyridazin-3-ones. Part 5. Exploration of pyridazinones containing 6-amino-substituents Bioorg Med Chem Lett 18 5635-5639
  • [9] Doi S(2002)QSAR studies on biological activity of piritrexim analogues against pc DHFR Bioorg Med Chem 10 2919-2926
  • [10] Hase Y(2008)Prediction of melting point for drug-like compounds using principal component-genetic algorithm-artificial neural network Bull Korean Chem Soc 29 833-841
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