Birchall Kristian, Gillet Valerie J, Willett Peter, Ducrot Pierre, Luttmann Claude
Krebs Institute for Biomolecular Research and Department of Information Studies, University of Sheffield, Sheffield S1 4DP, United Kingdom.
J Chem Inf Model. 2009 Jun;49(6):1330-46. doi: 10.1021/ci900078h.
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.
本文描述了一个项目，该项目旨在将片段子结构对之间生物电子等排体等效性的明确信息纳入基于相似性的虚拟筛选系统中。来自BIOSTER数据库的数据表明，简化图提供了一种简单的方法来编码已知的生物电子等排体等效性，且该方式可在相似性搜索过程中使用。对WOMBAT数据库进行的骨架跃迁实验表明，纳入此类信息能够识别参考结构与数据库中活性结构之间的相似性，这些活性结构包含不同但等效的片段子结构。然而，此类等效性也会导致参考结构与非活性结构之间的相似性，而后一种等效性可能会掩盖那些涉及活性结构的等效性。这给在基于相似性的虚拟筛选中常规使用生物电子等排片段信息带来了严重问题。
