Protein Crowding Affects Hydration Structure and Dynamics

Abstract

The effect of protein crowding on the structure and dynamics of water was examined from explicit solvent molecular dynamics simulations of a series of protein G and protein G/villin systems at different protein concentrations. Hydration structure was analyzed in terms of radial distribution functions, three-dimensional hydration sites, and preservation of tetrahedral coordination. Analysis of hydration dynamics focused on self-diffusion rates and dielectric constants as a function of crowding. The results show significant changes in both structure and dynamics of water under highly crowded conditions. The structure of water is altered mostly beyond the first solvation shell. Diffusion rates and dielectric constants are significantly reduced following linear trends as a function of crowding reflecting highly constrained water in crowded environments. The reduced dynamics of diffusion is expected to be strongly related to hydrodynamic properties of crowded cellular environments while the reduced dielectric constant under crowded conditions has implications for the stability of biomolecules in crowded environments. The results from this study suggest a prescription for modeling solvation in simulations of cellular environments.

Soft interactions and crowding

“…Molecular dynamic simulations showed that the backbone fluctuations of CI2 increase in lysozyme, which correlates with its destabilizing effect . Harada et al (2012) used molecular dynamics to show that protein crowders reduce the dielectric constant of the solution. This decrease would diminish the hydrophobic effect while enhancing hydrogen bond strength.…”

Biological Water Dynamics and Entropy: A Biophysical Origin of Cancer and Other Diseases

“…In a recent KITA investigation of peptide substrate binding to a human metalloproteinase, no conclusion was reached as to whether water motions preceded or followed enzyme motions [23]. In contrast, numerous studies of protein folding and of proteins and nucleic acids passing through their glass transition temperatures (the temperature below which the hydrated macromolecule shows highly restricted movement and little or no biological activity) have generally indicated that more-rapid changes in local water structure precede the slower, major conformational changes of the macromolecules [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36].…”

“…Could water CDs provide a physical basis for overcoming both the kT paradox and the intracellular crowding problem [28,29,31,[164][165][166][167][168][169][170][171][172]? The term kT requirement, where k is the Boltzmann constant and T is temperature (deg K), relates generally to the temperature dependence of chemical reaction rates, and the need to impart enough energy to biological molecules in cells to achieve such reactions at physiological temperatures, without resorting to thermal diffusion (i.e., heating up the reactants).…”

“…As noted in Section 2 above, experiments with new spectroscopic techniques that enable study of biological systems on time scales down to picoseconds indicate that large-scale motions of proteins and nucleic acids are determined by fluctuations in the hydration shell, which are controlled by solvent viscosity and hydration, and are absent in a dehydrated protein [14,[17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]36]. If changes in interfacial water structure drive biomacromolecular conformational changes, then biological systems must have means to vary interfacial water structure and properties (within properly-functioning, life-enabling limits) to carry out their wide range of life-sustaining activities.…”

Molecular simulations of cellular processes

“…Albeit popular, Eq. 2 and most treatments of hydrodynamic interactions do not account for the perturbation of the solvent caused by crowding agents (Harada et al 2012;Mukherjee et al 2015;Wang et al 2017b) or by protein-specific effects (Huang et al 2016). …”