Hydration Dynamics in a Partially Denatured Ensemble of the Globular Protein Human α-Lactalbumin Investigated with Molecular Dynamics Simulations

Atomistic molecular dynamics simulations are used to probe changes in the nature and subnanosecond dynamical behavior of solvation waters that accompany partial denaturation of the globular protein, human α-lactalbumin. A simulated ensemble of subcompact conformers, similar to the molten globule state of human α-lactalbumin, demonstrates a marginal increase in the amount of surface solvation relative to the native state. This increase is accompanied by subtle but distinct enhancement in surface water dynamics, less favorable protein-water interactions, and a marginal decrease in the anomalous behavior of solvation water dynamics. The extent of solvent influx is not proportional to the increased surface area, and the partially denatured conformers are less uniformly solvated compared to their native counterpart. The observed solvation in partially denatured conformers is lesser in extent compared to earlier experimental estimates in molten globule states, and is consistent with more recent descriptions based on nuclear magnetic relaxation dispersion studies.