Tanrikulu Yusuf, Schneider Gisbert
Institute of Organic Chemistry and Chemical Biology, Johann Wolfgang Goethe-University Frankfurt, Siesmayerstrasse 70, D-60323 Frankfurt, Germany.
Nat Rev Drug Discov. 2008 Aug;7(8):667-77. doi: 10.1038/nrd2615. Epub 2008 Jul 18.
Rational drug design is based on explicit or implicit structure-activity relationship models. Typically, receptor-based or ligand-based strategies are pursued, depending on the information available about known ligands and the receptor structure. Pseudoreceptor models combine the advantages of these two strategies and represent a unifying concept for both receptor mapping and ligand matching. They can provide an entry point for structure-based modelling in drug discovery projects that lack a high-resolution structure of the target. Here, we review the field of pseudoreceptor modelling techniques along with recent hit and lead finding applications, and critically discuss prerequisites, advantages and limitations of the various approaches.
合理药物设计基于明确或隐含的构效关系模型。通常，根据有关已知配体和受体结构的可用信息，采用基于受体或基于配体的策略。虚拟受体模型结合了这两种策略的优点，为受体图谱绘制和配体匹配提供了一个统一的概念。它们可以为缺乏目标高分辨率结构的药物发现项目中的基于结构的建模提供切入点。在此，我们回顾虚拟受体建模技术领域以及最近的命中和先导化合物发现应用，并批判性地讨论各种方法的先决条件、优点和局限性。
