Constructing virtual combinatorial fragment libraries based upon MDL Drug Data Report database  

作　　者：ZHANG Min SHENG ChunQuan XU Hui SONG YunLong ZHANG WanNian 

机构地区：[1]School of Pharmacy,Second Military Medical University,Shanghai 200433,China

出　　处：《Science China Chemistry》2007年第3期364-371,共8页中国科学（化学英文版）

基　　金：Supported by the National Natural Science Foundation of China (Grant No. 30430750);National 863 Project (Grant No. 2002AA233091)

摘　　要：Structural analysis of known drugs or drug-like compounds provides important information for drug design. The 142553 drug molecules in the MDL Drug Data Report database were analyzed, and then the common structural features were extracted. According to the common structural features, drug molecules were segmented into 32017 fragments, including 13642 ring fragments, 10076 linker fragments, and 8299 side chain fragments. These fragments were further used to establish three types of virtual combinatorial fragment libraries: a basic framework library containing 13574 rings; a linker library of 8051 linkers and a pharmacophore library of 34244 fragments combined by rings and side chains. After energy minimization, all fragments in the above three libraries maintain reasonable geometrical features and spatial conformations, and would be useful for building a virtual combinatorial database and de novo drug design.Structural analysis of known drugs or drug-like compounds provides important information for drug design. The 142553 drug molecules in the MDL Drug Data Report database were analyzed, and then the common structural features were extracted. According to the common structural features, drug molecules were segmented into 32017 fragments, including 13642 ring fragments, 10076 linker fragments, and 8299 side chain fragments. These fragments were further used to establish three types of virtual combinatorial fragment libraries: a basic framework library containing 13574 rings; a linker library of 8051 linkers and a pharmacophore library of 34244 fragments combined by rings and side chains. After energy minimization, all fragments in the above three libraries maintain reasonable geometrical features and spatial conformations, and would be useful for building a virtual combinatorial database and de novo drug design.

关 键 词：DRUG design FRAGMENT molecular DATABASE statistical analysis DRUG MOLECULE 

分 类 号：TP311.13[自动化与计算机技术—计算机软件与理论]