ADME evaluation in drug discovery. 2. Prediction of partition   coefficient by atom-additive approach based on atom-weighted solvent   accessible surface areas

doi:10.1021/ci034007m

CORC > 北京大学 > 化学与分子工程学院

	ADME evaluation in drug discovery. 2. Prediction of partition coefficient by atom-additive approach based on atom-weighted solvent accessible surface areas
	Hou, TJ ; Xu, XJ
刊名	journal of chemical information and computer sciences
	2003
关键词	CONSTANTS F-VALUES PHYSICOCHEMICAL PARAMETERS LOG-P MOLECULAR LIPOPHILICITY HYDROPHOBIC INTERACTIONS SOLVATION SYSTEM FIELD TOOL
DOI	10.1021/ci034007m
英文摘要	A novel method for the calculations of 1-octanol/water partition coefficient (log P) of organic molecules has been presented here. The method, SLOGP v1.0, estimates the log P values by summing the contribution of atom-weighted solvent accessible surface areas (SASA) and correction factors. Altogether 100 atom/group types were used to classify atoms with different chemical environments, and two correlation factors were used to consider the intermolecular hydrophobic interactions and intramolecular hydrogen bonds. Coefficient values for 100 atom/group and two correction factors have been derived from a training set of 1850 compounds. The parametrization procedure for different kinds of atoms was performed as follows: first, the atoms in a molecule were defined to different atom/group types based on SMARTS language, and the correction factors were determined by substructure searching; then, SASA for each atom/group type was calculated and added; finally, multivariate linear regression analysis was applied to optimize the hydrophobic parameters for different atom/group types and correction factors in order to reproduce the experimental log P. The correlation based on the training set gives a model with the correlation coefficient (r) of 0.988, the standard deviation (SD) of 0.368 log units, and the absolute unsigned mean error of 0.261. Comparison of various procedures of log P calculations for the external test set of 138 organic compounds demonstrates that our method bears very good accuracy and is comparable or even better than the fragment-based approaches. Moreover, the atom-additive approach based on SASA was compared with the simple atom-additive approach based on the number of atoms. The calculated results show that the atom-additive approach based on SASA gives better predictions than the simple atom-additive one. Due to the connection between the molecular conformation and the molecular surface areas, the atom-additive model based on SASA may be a more universal model for log P estimation especially for large molecules.; Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; SCI(E); EI; PubMed; 0; ARTICLE; 3; 1058-1067; 43
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/200093]
专题	化学与分子工程学院
推荐引用方式 GB/T 7714	Hou, TJ,Xu, XJ. ADME evaluation in drug discovery. 2. Prediction of partition coefficient by atom-additive approach based on atom-weighted solvent accessible surface areas[J]. journal of chemical information and computer sciences,2003.
APA	Hou, TJ,&Xu, XJ.(2003).ADME evaluation in drug discovery. 2. Prediction of partition coefficient by atom-additive approach based on atom-weighted solvent accessible surface areas.journal of chemical information and computer sciences.
MLA	Hou, TJ,et al."ADME evaluation in drug discovery. 2. Prediction of partition coefficient by atom-additive approach based on atom-weighted solvent accessible surface areas".journal of chemical information and computer sciences (2003).