Solvation Energetic Costs of Cognate Binding Site Formation.

ABSTRACT: Structural fluctuations of proteins can reveal alternate binding site conformations or cryptic pockets that may be exploited to discover novel, tightly bound chemical compounds. While significant effort has been dedicated to the exploration of protein conformational space, the thermodynamic role of solvation and how it is coupled to a protein's structural fluctuations, particularly in binding site formation, has not been well characterized. In this study, we examine how binding site solvation energetics differ between unligated rigid cavities restrained about their ligand-bound conformations and the same cavities with flexible side chains free to explore conformational space in molecular dynamics simulations. We find that, on average, the solvation energy of flexible b

SUBMITTER: Ji Y 

PROVIDER: S-EPMC12421683 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature