Clark D E, Westhead D R, Sykes R A, Murray C W
Proteus Molecular Design Ltd., Macclesfield, Cheshire, U.K.
J Comput Aided Mol Des. 1996 Oct;10(5):397-416. doi: 10.1007/BF00124472.
Two new computational tools, PRO_PHARMEX and PRO_SCOPE, for use in active-site-directed searching of 3D databases are described. PRO_PHARMEX is a flexible, graphics-based program facilitating the extraction of pharmacophores from the active site of a target macromolecule. These pharmacophores can then be used to search a variety of databases for novel lead compounds. Such searches can often generate many 'hits' of varying quality. To aid the user in setting priorities for purchase, synthesis or testing, PRO_SCOPE can be used to dock molecules rapidly back into the active site and to assign them a score using an empirical scoring function correlated to the free energy of binding. To illustrate how these tools can add value to existing 3D database software, their use in the design of novel thrombin inhibitors is described.
本文介绍了两种用于三维数据库活性位点定向搜索的新计算工具PRO_PHARMEX和PRO_SCOPE。PRO_PHARMEX是一个灵活的、基于图形的程序，有助于从目标大分子的活性位点提取药效团。然后，这些药效团可用于在各种数据库中搜索新型先导化合物。此类搜索通常会产生许多质量各异的“命中”结果。为帮助用户确定购买、合成或测试的优先级，PRO_SCOPE可用于将分子快速对接回活性位点，并使用与结合自由能相关的经验评分函数为它们打分。为说明这些工具如何为现有的三维数据库软件增加价值，本文描述了它们在新型凝血酶抑制剂设计中的应用。
