Zhang Initiative Research Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
J Chem Inf Model. 2013 Aug 26;53(8):1880-92. doi: 10.1021/ci400052w. Epub 2013 May 8.
Water molecules are routinely included in molecular docking methods and protocols because of their important role in mediating ligand protein interactions. However, it is still unclear that the inclusion of explicit water molecules improves docking accuracy. To explore the effect of including key water molecules on docking accuracy and performance, we participated in the CSARdock 2011 benchmark exercise. This exercise provides a valuable opportunity for researchers to test their docking programs, methods, and protocols in a blind testing environment. The benchmark exercise and its analysis presented in this paper showed that the performance of current docking programs can be improved by incorporating carefully selected water molecules. Our study showed that water mapping calculations can be used to select key water molecules from experimentally identified water positions for molecular dockings. We have observed that inclusion of all binding site water molecules led to reduced performance and erroneous results. Moreover, an overall improvement in binding pose prediction was achieved when computationally selected water molecules are included during docking simulations. The improvement in the docking performance by including water molecules also depends on protein system, chemical class of ligand, docking method, and scoring function.
水分子在介导配体-蛋白质相互作用方面起着重要作用，因此在分子对接方法和方案中通常会包含水分子。然而，目前尚不清楚包含明确的水分子是否能提高对接的准确性。为了探索包含关键水分子对接准确性和性能的影响，我们参加了 CSARdock 2011 基准测试。这项基准测试为研究人员在盲测环境下测试他们的对接程序、方法和方案提供了一个有价值的机会。本文介绍的基准测试及其分析表明，通过精心选择的水分子，可以提高当前对接程序的性能。我们的研究表明，水分子映射计算可以用于从实验确定的水分子位置中选择关键水分子进行分子对接。我们观察到，包含所有结合位点的水分子会导致性能下降和错误的结果。此外，当在对接模拟过程中包含计算选择的水分子时，整体的结合构象预测得到了改善。包含水分子对接性能的提高还取决于蛋白质系统、配体的化学类别、对接方法和打分函数。
