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Site-Specific Hydration Dynamics of Globular Proteins and the Role of Constrained Water in Solvent Exchange with Amphiphilic Cosolvents
journal contribution
posted on 2012-05-17, 00:00 authored by John T. King, Evan J. Arthur, Charles L. Brooks, Kevin J. KubarychThe thermodynamic driving forces for protein folding,
association,
and function are often determined by protein–water interactions.
With a novel covalently bound labeling approach, we have used sensitive
vibrational probes, site-selectively conjugated to two lysozyme variantsin
conjunction with ultrafast two-dimensional infrared (2D-IR) spectroscopyto
investigate directly the protein–water interface. By probing
alternatively a topologically flat, rigid domain and a flexible domain,
we find direct experimental evidence for spatially heterogeneous hydration
dynamics. The hydration environment around globular proteins can vary
from exhibiting bulk-like hydration dynamics to dynamically constrained
water, which results from stifled hydrogen bond switching dynamics
near extended hydrophobic surfaces. Furthermore, we leverage preferential
solvation exchange to demonstrate that the liberation of dynamically
constrained water is a sufficient driving force for protein–surface
association reactions. These results provide an intuitive picture
of the dynamic aspects of hydrophobic hydration of proteins, illustrating
an essential function of water in biological processes.