Effect of Water Networks On Ligand Binding: Computational Predictions vs Experiments.

ABSTRACT: Rational drug design focuses on the explanation and prediction of complex formation between therapeutic targets and small-molecule ligands. As a third and often overlooked interacting partner, water molecules play a critical role in the thermodynamics of protein-ligand binding, impacting both the entropy and enthalpy components of the binding free energy and by extension, on-target affinity and bioactivity. The community has realized the importance of binding site waters, as evidenced by the number of computational tools to predict the structure and thermodynamics of their networks. However, quantitative experimental characterization of relevant protein-ligand-water systems, and consequently the validation of these modeling methods, remains challenging. Here, we investigated the impact of

SUBMITTER: Szalai TV 

PROVIDER: S-EPMC11632780 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature