an in silico method for screening nicotine derivatives as cytochrome p450 2a6 selective inhibitors based on kernel partial least squares在硅片的方法筛选尼古丁衍生品作为细胞色素p450 2 a6基于核偏最小二乘的选择性抑制剂.pdfVIP

Int. J. Mol. Sci. 2007, 8, 166-179 International Journal of Molecular Sciences ISSN 1422-0067 © 2007 by MDPI /ijms/ An In Silico Method for Screening Nicotine Derivatives as Cytochrome P450 2A6 Selective Inhibitors Based on Kernel Partial Least Squares Yonghua Wang 1,*, Yan Li 2 and Bin Wang 1 1 School of Life Science and Technology, Dalian Fisheries University, Dalian 116023, China. 2 School of Chemical Engineering, Dalian University of Technology, Dalian 116012, China. * Author to whom correspondence should be addressed. E-mail: yhwang@ Received: 13 December 2006 / Accepted: 29 January 2007 / Published: 28 February 2007 Abstract: Nicotine and a variety of other drugs and toxins are metabolized by cytochrome P450 (CYP) 2A6. The aim of the present study was to build a quantitative structure-activity relationship (QSAR) model to predict the activities of nicotine analogues on CYP2A6. Kernel partial least squares (K-PLS) regression was employed with the electro-topological descriptors to build the computational models. Both the internal and external predictabilities of the models were evaluated with test sets to ensure their validity and reliability. As a comparison to K-PLS, a standard PLS algorithm was also applied on the same training and test sets. Our results show that the K-PLS produced reasonable results that outperformed the PLS model on the datasets. The obtained K-PLS mode