Dynamics of Hydration Water Plays a Key Role in Determining the Binding Thermodynamics of Protein Complexes
Open Access
- 18 August 2017
- journal article
- research article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 7 (1), 1-10
- https://doi.org/10.1038/s41598-017-09466-w
Abstract
Interfacial waters are considered to play a crucial role in protein–protein interactions, but in what sense and why are they important? Here, using molecular dynamics simulations and statistical thermodynamic analyses, we demonstrate distinctive dynamic characteristics of the interfacial water and investigate their implications for the binding thermodynamics. We identify the presence of extraordinarily slow (~1,000 times slower than in bulk water) hydrogen-bond rearrangements in interfacial water. We rationalize the slow rearrangements by introducing the “trapping” free energies, characterizing how strongly individual hydration waters are captured by the biomolecular surface, whose magnitude is then traced back to the number of water–protein hydrogen bonds and the strong electrostatic field produced at the binding interface. We also discuss the impact of the slow interfacial waters on the binding thermodynamics. We find that, as expected from their slow dynamics, the conventional approach to the water-mediated interaction, which assumes rapid equilibration of the waters’ degrees of freedom, is inadequate. We show instead that an explicit treatment of the extremely slow interfacial waters is critical. Our results shed new light on the role of water in protein–protein interactions, highlighting the need to consider its dynamics to improve our understanding of biomolecular bindings.This publication has 54 references indexed in Scilit:
- Transmembrane Protein Activation Refined by Site‐Specific Hydration DynamicsAngewandte Chemie-International Edition, 2013
- Magnitude and Molecular Origin of Water Slowdown Next to a ProteinJournal of the American Chemical Society, 2012
- Correlated structural kinetics and retarded solvent dynamics at the metalloprotease active siteNature Structural & Molecular Biology, 2011
- Site-resolved measurement of water-protein interactions by solution NMRNature Structural & Molecular Biology, 2011
- MM-PBSA Captures Key Role of Intercalating Water Molecules at a Protein−Protein InterfaceJournal of Chemical Theory and Computation, 2009
- Role of the Active-Site Solvent in the Thermodynamics of Factor Xa Ligand BindingJournal of the American Chemical Society, 2008
- Comparison of multiple Amber force fields and development of improved protein backbone parametersProteins-Structure Function and Bioinformatics, 2006
- A theoretical analysis on hydration thermodynamics of proteinsThe Journal of Chemical Physics, 2006
- Molecular dynamics with coupling to an external bathThe Journal of Chemical Physics, 1984
- Comparison of simple potential functions for simulating liquid waterThe Journal of Chemical Physics, 1983