MOLECULAR RECOGNITION OF RECEPTOR-SITES USING A GENETIC ALGORITHM WITH A DESCRIPTION OF DESOLVATION
MOLECULAR RECOGNITION OF RECEPTOR-SITES USING A GENETIC ALGORITHM WITH A DESCRIPTION OF DESOLVATION
复制标题
DOI：
10.1016/s0022-2836(95)80037-9
复制
发表时间：
1995-01-06
影响因子：
5.6
通讯作者：
GLEN, RC
中科院分区：
文献类型：
--
作者：
JONES, G;WILLETT, P;GLEN, RC
了解大分子生物受体识别小分子底物或抑制剂的原理是一项重大努力的主题。这在已知受体结构的合理药物设计中至关重要（“对接”问题）。目前的理论方法利用结合配体的空间和静电相互作用的模型，最近已纳入构象的灵活性。我们报告的结果基于软件，使用遗传算法，使用进化策略，在探索充分的构象的灵活性与部分灵活性的蛋白质的配体，并满足基本要求，即配体必须取代松散的结合水的结合。结果报告五个测试系统显示出良好的协议与实验数据。该算法的设计提供了深入了解分子识别机制。
Understanding the principles whereby macromolecular biological receptors can recognise small molecule substrates or inhibitors is the subject of a major effort. This is of paramount importance in rational drug design where the receptor structure is known (the ''docking'' problem). Current theoretical approaches utilise models of the steric and electrostatic interaction of bound ligands and recently conformational flexibility has been incorporated. We report results based on software using a genetic algorithm that uses an evolutionary strategy in exploring the full conformational flexibility of the ligand with partial flexibility of the protein, and which satisfies the fundamental requirement that the ligand must displace loosely bound water on binding. Results are reported on five test systems showing excellent agreement with experimental data. The design of the algorithm offers insight into the molecular recognition mechanism.