Uncovering water effects in protein-ligand recognition: importance in the second hydration shell and binding kinetics.

ABSTRACT: Developing a ligand with high affinity for a specific protein target is essential for drug design, and water molecules are well known to play a key role in protein-drug recognition. However, predicting the role of particularly ordered water molecules in drug binding remains challenging. Furthermore, hydration free energy contributed from the water network, including the second shell of water molecules, is far from being well studied. In this research we focused on these aspects to accurately and efficiently evaluate water effects in protein-ligand binding affinity. We developed a new strategy using a free-energy calculation method, VM2. We successfully predicted the stable ordered water molecules in a number of protein systems: PDE 10a, HSP90, tryptophan synthase (TRPS), CDK2 and Factor Xa

SUBMITTER: Chen W 

PROVIDER: S-EPMC9970846 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature