利用SMILES字符串构建虚拟组合文库以发现潜在的结构多样的过氧化物酶体增殖物激活受体（PPAR）调节剂。

Construction of a virtual combinatorial library using SMILES strings to discover potential structure-diverse PPAR modulators.

作者信息

Liao Chenzhong, Liu Bing, Shi Leming, Zhou Jiaju, Lu Xian-Ping

机构信息

Chipscreen Biosciences, Ltd. Research Institute of Tsinghua University, Suite C301, P.O. Box 28, Shenzhen, Guangdong 518057, China.

出版信息

Eur J Med Chem. 2005 Jul;40(7):632-40. doi: 10.1016/j.ejmech.2005.02.006. Epub 2005 Mar 31.

DOI:10.1016/j.ejmech.2005.02.006

PMID:15935898

Abstract

Based on the structural characters of PPAR modulators, a virtual combinatorial library containing 1226,625 compounds was constructed using SMILES strings. Selected ADME filters were employed to compel compounds having poor drug-like properties from this library. This library was converted to sdf and mol2 files by CONCORD 4.0, and was then docked to PPARgamma by DOCK 4.0 to identify new chemical entities that may be potential drug leads against type 2 diabetes and other metabolic diseases. The method to construct virtual combinatorial library using SMILES strings was further visualized by Visual Basic.net that can facilitate the needs of generating other type virtual combinatorial libraries.

摘要

基于PPAR调节剂的结构特征，使用SMILES字符串构建了一个包含1226625种化合物的虚拟组合库。采用选定的ADME筛选标准从该库中排除具有不良类药性质的化合物。该库通过CONCORD 4.0转换为sdf和mol2文件，然后通过DOCK 4.0与PPARγ对接，以识别可能成为治疗2型糖尿病和其他代谢疾病潜在药物先导物的新化学实体。使用SMILES字符串构建虚拟组合库的方法通过Visual Basic.net进一步可视化，这有助于满足生成其他类型虚拟组合库的需求。