Understanding the role of hydrogen bonds in water dynamics and protein stability

Abstract

The mechanisms of cold and pressure denaturation of proteins are a matter of debate, but it is commonly accepted that water plays a fundamental role in the process. It has been proposed that the denaturation process is related to an increase of hydrogen bonds among hydration water molecules. Other theories suggest that the causes of denaturation are the density fluctuations of surface water, or the destabilization of hydrophobic contacts as a consequence of water molecule inclusions inside the protein, especially at high pressures. We review some theories that have been proposed to give insight into this problem, and we describe a coarse-grained model of water that compares well with experiments for proteins' hydration water. We introduce its extension for a homopolymer in contact with the water monolayer and study it by Monte Carlo simulations in an attempt to understand how the interplay of water cooperativity and interfacial hydrogen bonds affects protein stability.

Finite-size scaling investigation of the liquid-liquid critical point in ST2 water and its stability with respect to crystallization

“…[22][23][24] It would be consistent with a range of thermodynamical and dynamical anomalies [25][26][27][28][29][30][31][32][33] and experiments. [34][35][36][37] Many more computer simulations investigating the phenomenology of the liquid-liquid critical point (LLCP) have been performed since then.…”

In Silico Evidence That Protein Unfolding is a Precursor of Protein Aggregation

“…[34] (B) The folding moves are (1) pivot moves, (2) corner flips and (3) crankshaft moves same as used in [43] but in 2D. [40,52] The design scheme leads to sequences which are not perfectly hydrophilic on the surface and hydrophobic into the core, consistent with what is observed in real proteins. [75,76] The hydropathy of the designed protein surface and core is shown in Figure 2, while the full amino acid composition of each sequence is shown in the supplementary Figure S6.…”

“…[42][43][44][45] The protein is embedded in water, explicitly modelled via the Franzese-Stanley water model which expressly accounts for many-body interactions and has been proven to reproduce, at least qualitatively, the thermodynamic and dynamic behaviour of water, [46][47][48][49][50] including its interplay with proteins. [34,35,40,[51][52][53] The coarse-grain representation of the water molecules, adopted to describe water at a constant number of molecules N, constant temperature T and constant pressure P, replaces the coordinates and orientations of the water molecules by a continuous density field and discrete bonding variables, respectively. The discrete variables describe the local hydrogen-bond (HB) formation and its cooperativity, leading to a local opentetrahedral structure of the water molecules.…”

Role of cavities and hydration in the pressure unfolding of T 4 lysozyme

“…One is that pressure alters the waterwater hydrogen bonding energetics such that the unfolded state is favored at high pressure (11,12,50). Pressure-driven changes in the energetics of solvation of hydrophobic surfaces and of charged side chains have been argued to be significant (11,12,14).…”