Hydrogen-bond dynamics at the bio–water interface in hydrated proteins: a molecular-dynamics study

Abstract

Water is fundamental to the biochemistry of enzymes. It is well known that without a minimum amount of water, enzymes are not biologically active. Bare minimal solvation for biological function corresponds to about a single layer of water covering enzymes' surfaces. Many contradictory studies on protein-hydration-water-coupled dynamics have been published in recent decades. Following prevailing wisdom, a dynamical crossover in hydration water (at around 220 K for hydrated lysozymes) can trigger larger-amplitude motions of the protein, activating, in turn, biological functions. Here, we present a molecular-dynamics-simulation study on a solvated model protein (hen egg-white lysozyme), in which we determine, inter alia, the relaxation dynamics of the hydrogen-bond network between the protein and its hydration water molecules on a residue-per-residue basis. Hydrogen-bond breakage/formation kinetics is rather heterogeneous in temperature dependence (due to the heterogeneity of the free-energy surface), and is driven by the magnitude of thermal motions of various different protein residues which provide enough thermal energy to overcome energy barriers to rupture their respective hydrogen bonds with water. In particular, arginine residues exhibit the highest number of such hydrogen bonds at low temperatures, losing almost completely such bonding above 230 K. This suggests that hydration water's dynamical crossover, observed experimentally for hydrated lysozymes at ∼220 K, lies not at the origin of the protein residues' larger-amplitude motions, but rather arises as a consequence thereof. This highlights the need for new experimental investigations, and new interpretations to link protein dynamics to functions, in the context of key interrelationships with the solvation layer.

How Ligand Binding Affects the Dynamical Transition Temperature in Proteins

“…The number of these hydrogen bonds decayed with increasing temperature, once the transition temperature had been crossed. This also parallels comparable observations made previously for lysozyme …”

“…To study how ligand binding influences the MSD, which typically rises for proteins linearly after crossing the transition temperature, we simulated the high affinity ATP binding mutant of the ϵ subunit from thermophilic Bacillus PS3 in the ATP bound and ligand‐free states at temperatures ranging from 20 K to 300 K in increments of 10 K. One difference in our fully hydrated simulations to some experimental setups is the lack of a powder state. In previously reported simulations, both approaches have been used (both solvated powder, in which the quantity of water corresponds to the experimental hydration level, and the powder‐free, fully solvated state); irrespective of the precise treatment (powder or solvation) of the systems, these studies typically led to similar results with respect to the prediction of the protein transition temperature. The transition temperature has been found to be attenuated, but not suppressed, for protein domains not facing the water surface at the protein‐water interface; however, it is important to note that water properties in a powder are different than in bulk solution and also that the water model has been shown to influence the transition temperature .…”

“…Using molecular dynamics (MD) simulations, the transition temperature and MSD below and above this temperature have been studied for a range of folded and intrinsically disordered proteins, DNA and RNA . In this study, we simulated the high affinity ATP binding R103A/R115A mutant of the ϵ subunit from thermophilic Bacillus PS3 when bound to ATP and free of ligand, at temperatures ranging from 20–300 K, in order to calculate the transition temperatures in both states.…”

A Quantitative Comparison of the Counting Significance of van Hove Integral Spectroscopy and Quasielastic Neutron Scattering

“…Among the available techniques, neutron scattering is unique in probing the motion of atomic nuclei, rather than measuring the response of the electrons to the nuclear dynamics, which is the case for most other spectroscopies. This direct type of interaction makes the comparison between neutron scattering and classical molecular dynamics simulations a successful and straightforward combination [9][10][11] .…”

Low temperature dependence of protein-water interactions on barstar surface: A nano-scale modelling

“…The magnitude and molecular origin of this retardation are still topics for further study [26][27][28][29]. Moreover some authors state that the heterogeneous scenario biological water presents is due to the heterogeneity of the protein surface itself in contrast to the more homogeneous nature of the solvent, suggesting that the hydrogen-bond dynamics between the protein and the hydration water is governed by the protein [30].…”