Poornima C S, Dean P M
Department of Pharmacology, University of Cambridge, UK.
J Comput Aided Mol Des. 1995 Dec;9(6):500-12. doi: 10.1007/BF00124321.
Water is known to play an important role in the recognition and stabilization of the interaction between a ligand and its site. This has important implications for drug design. Analyses of 19 high-resolution crystal structures of protein-ligand complexes reveal the multiple hydrogen-bonding feature of water molecules mediating protein-ligand interactions. Most of the water molecules (nearly 80%) involved in bridging the protein and the ligand can make three or more hydrogen bonds when distance and bond angles are used as criteria to define hydrogen-bonding interactions. Isotropic B-factors have been used to take into account the mobility of water molecules. The water molecules at binding sites bridge the protein and ligand, and interact with other water molecules to form a complex network of interconnecting hydrogen bonds. Some water molecules at the site do not directly bridge between the protein and the ligand, but may contribute indirectly to the stability of the complex by holding bridging water molecules in the right position through a network of hydrogen bonds. These water networks are probably crucial for the stability of the protein-ligand complex and are important for any site-directed drug design strategies.
众所周知，水在配体与其结合位点之间相互作用的识别和稳定中起着重要作用。这对药物设计具有重要意义。对19个蛋白质-配体复合物的高分辨率晶体结构分析揭示了介导蛋白质-配体相互作用的水分子的多重氢键特征。当以距离和键角作为定义氢键相互作用的标准时，参与连接蛋白质和配体的大多数水分子（近80%）可以形成三个或更多氢键。各向同性B因子已被用于考虑水分子的流动性。结合位点处的水分子连接蛋白质和配体，并与其他水分子相互作用形成一个相互连接的氢键复杂网络。该位点的一些水分子不直接在蛋白质和配体之间形成桥梁，但可能通过氢键网络将桥连水分子保持在正确位置，从而间接有助于复合物的稳定性。这些水网络可能对蛋白质-配体复合物的稳定性至关重要，并且对任何定点药物设计策略都很重要。
