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论文类型：期刊论文

发表时间：2009-04-01

发表刊物：JOURNAL OF MOLECULAR GRAPHICS & MODELLING

收录刊物：SCIE、EI、PubMed

卷号：27

期号：7

页面范围：829-835

ISSN号：1093-3263

关键字：Support vector machine; Molecular dynamics; Mechanism of toxic action; Uncoupling activity; Polar narcotics

摘要：In recent years, both classification models and quantitative structure-activity relationships (QSARs) have been developed to discriminate the acute toxicity of polar narcotics and uncouplers. One of fundamental issues is how to select and interpret the molecular descriptors used in both methods. In this work, we first employed support vector machine on a dataset containing 155 polar narcotics and 19 uncouplers to filter the predictive hydrophobic and hydrogen bonding descriptors. Molecular dynamics simulations were then conducted to investigate the behavior of salicylate and pentachlorophenol molecules in the context of a palmitoyl-oleoyl-phosphatidylcholine lipid bilayer. The results demonstrated that their equilibrium properties in the lipid bilayer were closely associated with hydrophobic and hydrogen bonding descriptors. The preferable occupations of these molecules in the lipid bilayer were discussed in terms of their modes of toxic action. The observations from molecular dynamics simulations facilitated to elucidate the mechanism of polar narcotics and uncouplers. Crown Copyright (C) 2009 Published by Elsevier Inc. All rights reserved.