Decoding BCL6 Inhibitors: Computational Insights into the Impact of Water Networks on Potency.

ABSTRACT: Water molecules in the binding site can have a critical role in small molecule binding to proteins and are an important consideration in structure-based drug design. Water networks have additional complexity as displacing one water molecule has subsequent effects on the remaining network. Modification of a lead compound that disrupts a water network can have beneficial or detrimental impacts on potency and this outcome is impossible to determine experimentally without time-consuming synthesis of the new compound. Computational methods are ideally suited to study the interplay between ligand optimization and water displacement by predicting the effect of structural changes on both the activity of the compound and the stability of neighboring water molecules. We used Grand Canonical Monte Ca

SUBMITTER: Hares DE 

PROVIDER: S-EPMC12458693 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature