Roles of Hydration in Protein-Ligand Binding: Passive or Active Participant?

ABSTRACT: Hydration is a critical yet often underappreciated factor that influences protein dynamics in solution, with direct effects on structure, stability, and interactions such as ligand binding. Native mass spectrometry (nMS) enables the analysis of biomolecules in their solution states, which are shaped by cofactors, osmolytes, ligands, and notably, hydration. Here, we employ variable-temperature electrospray ionization to address a central question in molecular biophysics: does hydration act as a passive background solvent or as an active participant in modulating ligand binding? To investigate these effects, temperature-dependent changes in average charge state (Z_avg), ADP equilibrium binding affinities (K_a), and enthalpy-entropy compensation (EEC) for the

SUBMITTER: Evans KA 

PROVIDER: S-EPMC12516730 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature