Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, University of Dundee, Dow Street, Dundee, DD1 5EH, UK.
J Comput Aided Mol Des. 2021 Oct;35(10):1025-1036. doi: 10.1007/s10822-021-00416-3. Epub 2021 Aug 30.
Water molecules play a crucial role in protein-ligand binding, and many tools exist that aim to predict the position and relative energies of these important, but challenging participants of biomolecular recognition. The available tools are, in general, capable of predicting the location of water molecules. However, predicting the effects of their displacement is still very challenging. In this work, a linear-scaling quantum mechanics-based approach was used to assess water network energetics and the changes in network stability upon ligand structural modifications. This approach offers a valuable way to improve understanding of SAR data and help guide compound design.
水分子在蛋白质-配体结合中起着至关重要的作用，目前已经有许多工具旨在预测这些在生物分子识别中重要但具有挑战性的参与者的位置和相对能量。现有的工具通常能够预测水分子的位置。然而，预测它们的位移的影响仍然非常具有挑战性。在这项工作中，使用基于线性标度量子力学的方法来评估水网络的能量学以及配体结构修饰对网络稳定性的变化。这种方法提供了一种有价值的方法来帮助提高对 SAR 数据的理解并指导化合物设计。
