Virtual screening and rational drug design method using structure generation system based on 3D-QSAR and docking

被引：5

作者：

Chen, HF

Dong, XC

Zen, BS

Gao, K

Yuan, SG

Panaye, A

Doucet, JP

Fan, BT

机构：

[1] Univ Paris 07, CNRS UMR7086, ITODYS, F-75005 Paris, France

[2] Chinese Acad Sci, Shanghai Inst Organ Chem, Comp Sci Lab, Shanghai 200032, Peoples R China

[3] Lanzhou Univ, State Key Lab Appl Organ Chem, Lanzhou 730000, Peoples R China

来源：

SAR AND QSAR IN ENVIRONMENTAL RESEARCH | 2003年 / 14卷 / 04期

基金：

中国国家自然科学基金;

关键词：

drug design; structure generation; 3D-QSAR; docking; virtual screening;

D O I：

10.1080/1062936032000101493

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

An efficient virtual and rational drug design method is presented. It combines virtual bioactive compound generation with 3D-QSAR model and docking. Using this method, it is possible to generate a lot of highly diverse molecules and find virtual active lead compounds. The method was validated by the study of a set of anti-tumor drugs. With the constraints of pharmacophore obtained by DISCO implemented in SYBYL 6.8, 97 virtual bioactive compounds were generated, and their anti-tumor activities were predicted by CoMFA. Eight structures with high activity were selected and screened by the 3D-QSAR model. The most active generated structure was further investigated by modifying its structure in order to increase the activity. A comparative docking study with telomeric receptor was carried out, and the results showed that the generated structures could form more stable complexes with receptor than the reference compound selected from experimental data. This investigation showed that the proposed method was a feasible way for rational drug design with high screening efficiency.

引用

页码：251 / 264

页数：14

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