Use of Reduced Graphs To Encode Bioisosterism for Similarity-Based Virtual Screening

被引:19
作者
Birchall, Kristian [1 ,2 ]
Gillet, Valerie J. [1 ,2 ]
Willett, Peter [1 ,2 ]
Ducrot, Pierre [3 ]
Luttmann, Claude [4 ]
机构
[1] Univ Sheffield, Krebs Inst Biomol Res, Sheffield S1 4DP, S Yorkshire, England
[2] Univ Sheffield, Dept Informat Studies, Sheffield S1 4DP, S Yorkshire, England
[3] Discngine, F-93230 Romainville, France
[4] Sanofi Aventis, Chem & Analyt Sci, F-94400 Vitry Sur Seine, France
关键词
EVOLVING INTERPRETABLE STRUCTURE; DRUG DESIGN; MOLECULAR MODIFICATION; CHEMICAL REPLACEMENTS; CRYSTALLOGRAPHIC DATA; IDENTIFICATION; OPTIMIZATION; DESCRIPTORS; INFORMATION; CHEMISTRY;
D O I
10.1021/ci900078h
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
This paper describes a project to include explicit information about bioisosteric equivalences between pairs of fragment substructures in a system for similarity-based virtual screening. Data from the BIOSTER database show that reduced graphs provide a simple way of encoding known bioisosteric equivalences in a manner that can be used during similarity searching. Scaffold-hopping experiments with the WOMBAT database show that including such information enables similarities to be identified between the reference structures and active structures from the database that contain different, but equivalent, fragment substructures. However, such equivalences also contribute to the similarities between the reference structures and inactives, and the latter equivalences can swamp those involving the actives. This presents serious problems for the routine use of information about bioisosteric fragments in similarity-based virtual screening.
引用
收藏
页码:1330 / 1346
页数:17
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