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-配体结合中发挥着至关重要的作用，并且存在许多工具旨在预测这些重要但具有挑战性的生物分子识别参与者的位置和相对能量。一般来说，可用的工具能够预测水分子的位置。然而，预测其位移的影响仍然非常具有挑战性。在这项工作中，使用基于线性尺度量子力学的方法来评估水网络能量学以及配体结构修饰时网络稳定性的变化。这种方法提供了一种宝贵的方法来提高对 SAR 数据的理解并帮助指导复合设计。