Heterogeneous and Allosteric Role of Surface Hydration for Protein-Ligand Binding.

ABSTRACT: Atomistic-level understanding of surface hydration mediating protein-protein interactions and ligand binding has been a challenge due to the dynamic nature of water molecules near the surface. We develop a computational method to evaluate the solvation free energy based on the density map of the first hydration shell constructed from all-atom molecular dynamics simulation and use it to examine the binding of two intrinsically disordered ligands to their target protein domain. One ligand is from the human protein, and the other is from the 1918 Spanish flu virus. We find that the viral ligand incurs a 6.9 kcal/mol lower desolvation penalty upon binding to the target, which is consistent with its stronger binding affinity. The difference arises from the spatially fragmented and nonuniform wa

SUBMITTER: Shi J 

PROVIDER: S-EPMC10848206 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature