Quantitative structure-activity relationship of organophosphate compounds based on molecular interaction fields descriptors

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• 作者：Jinsong Zhao ; ^{Jinsong.Zhao@gmail.com} ; ^{jszhao@mail.hzau.edu.cn} ; Shuxia Yu
• 关键词：Molecular interaction fields ; Quantitative structure&ndash ; activity relationship ; Multi-block partial least-squares ; Organophosphate compound ; Acetylcholinesterase
• 刊名：Environmental Toxicology and Pharmacology
• 出版年：2013
• 出版时间：March, 2013
• 年：2013
• 卷：35
• 期：2
• 页码：228-234
• 全文大小：1032 K

文摘

By using multi-block partial least-squares (MBPLS) method, quantitative structure-activity relationship (QSAR) between 35 organophosphate compounds (OP) and their 24 h acute toxicities towards the housefly (Musca nebulo L.) was built on the molecular interaction fields (MIF) descriptors, which were obtained with O, N and DRY as probes, and then normalised with block unscaled weights (BUW) technique. The best QSAR model had 8 principal components, with the coefficient of determination R² = 0.995 and that of leave-one-out cross-validation Q² = 0.865, and the corresponding standard deviation of error 0.076 and 0.361, respectively. Block importance in the prediction (BIP) for O, N and DRY probe were 1.030, 0.962 and 1.007, respectively. Contour map of variable coefficients showed that hydrogen bonding between the O atom in PO and the NH groups in acetylcholinesterase (AChE) played an important role in the interaction between OP and AChE. Meanwhile, the hydrophobicity of OP also had significant contribution. QSAR based on the MIF descriptors could be a potential means to interpret the mechanisms of ligand-receptor interaction when the receptor was well known.