Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research-NIPER, Sector 67, Punjab 160062, S.A.S Nagar, India.
Comput Math Methods Med. 2012;2012:541594. doi: 10.1155/2012/541594. Epub 2012 May 8.
Water molecules play a crucial role in mediating the interaction between a ligand and a macromolecule. The solvent environment around such biomolecule controls their structure and plays important role in protein-ligand interactions. An understanding of the nature and role of these water molecules in the active site of a protein could greatly increase the efficiency of rational drug design approaches. We have performed the comparative crystal structure analysis of aldose reductase to understand the role of crystal water in protein-ligand interaction. Molecular dynamics simulation has shown the versatile nature of water molecules in bridge H bonding during interaction. Occupancy and life time of water molecules depend on the type of cocrystallized ligand present in the structure. The information may be useful in rational approach to customize the ligand, and thereby longer occupancy and life time for bridge H-bonding.
水分子在介导配体和生物大分子之间的相互作用方面起着至关重要的作用。生物分子周围的溶剂环境控制着它们的结构，并在蛋白质-配体相互作用中起着重要作用。了解这些水分子在蛋白质活性部位的性质和作用，可以极大地提高合理药物设计方法的效率。我们已经进行了醛糖还原酶的比较晶体结构分析，以了解晶体水在蛋白质-配体相互作用中的作用。分子动力学模拟表明，水分子在相互作用过程中具有桥氢键的多功能性。水分子的占有率和寿命取决于结构中存在的共结晶配体的类型。这些信息可能有助于合理的方法来定制配体，从而延长桥氢键的占有率和寿命。
