水分子在药物设计中的作用  

The Role of Water Molecules in Drug Design

作　　者：周洋 陆小云 ZHOU Yang;LU Xiaoyun(College of Pharmacy,Jinan University,Guangzhou 510632,China)

机构地区：[1]暨南大学药学院,广东广州510632

出　　处：《药学进展》2022年第1期47-59,共13页Progress in Pharmaceutical Sciences

基　　金：国家自然科学基金(No.81922062)。

摘　　要：水分子广泛存在于药物靶标蛋白中,对于药物与靶标蛋白相互作用具有重要贡献。在药物设计中,替换水分子、与水分子形成相互作用,是优化化合物结构的有效方法。近年来,涌现出一系列通过合理替换水分子,提高化合物的结合活性、增强化合物的选择性、改善其药动学性质的案例。结合案例,对利用水分子指导化合物结构优化的方法以及研究水分子性质的方法和软件工具进行详细介绍,以期为化合物结构优化和创新药物研发提供参考。Water widely exists in organisms and plays important roles in the interactions between drug molecules and target proteins. In drug design, replacement of water molecules and interactions with them are considered to be effective methods for lead optimization. In recent years, there have been a series of cases applying the method to improve the binding activity of compounds, enhance the selectivity, and optimize the pharmacokinetic properties. Through these cases, the method of replacing water molecules for lead optimization as well as the theories and software tools for studying the properties of water molecules are introduced with detailed discussion so as to provide some reference for lead optimization and innovative drug development.

关 键 词：基于结构的药物设计 水分子替换 结构优化 选择性 

分 类 号：R914[医药卫生—药物化学]