Test of cold denaturation mechanism for proteins as a function of water's structure

We refine a protein model that reproduces fundamental aspects of protein thermodynamics. The model exhibits two transitions, hot and cold unfolding. The number of relevant parameters is reduced to three: 1) binding energy of folding relative to the orientational energy of bound water, 2) ratio of degrees of freedom between the folded and unfolded protein chain and 3) the number of water molecules that can access the hydrophobic parts of the protein interior. By increasing the...

The local structure of liquid water plays a key role in determining the anomalous properties of water. We run all-atom simulations for three microscopic water models, and use multiple order parameters to analyse the local structure of water. We identify three types of local structures. In addition to the well known low-density-liquid and high-density-liquid structures, the newly identified third type possesses an ultra high density and overcoordinated H-bonds. The existence o...

Folding kinetics of a lattice model of protein is studied. It uses the Random Energy Model for the intrachain couplings and a temperature dependent free energy of solvation derived from a realistic hydration model of apolar solutes. The folding times are computed using Monte Carlo simulations in the region of the phase diagram where the chain occurs in the native structure. These folding times are roughly equals for the temperatures of cold and warm denaturation for a large r...

The interactions of a protein, its phase behavior, and ultimately, its ability to function, are all influenced by the interactions between the protein and its hydration waters. Here we study proteins with a variety of sizes, shapes, chemistries, and biological functions, and characterize their interactions with their hydration waters using molecular simulation and enhanced sampling techniques. We find that akin to extended hydrophobic surfaces, proteins situate their hydratio...

We explain the physical basis of a model for small globular proteins with water interactions. The water is supposed to access the protein interior in an "all-or-none" manner during the unfolding of the protein chain. As a consequence of this mechanism (somewhat speculative), the model exhibits fundamental aspects of protein thermodynamics, as cold, and warm unfolding of the polypeptide chain, and hence decreasing the temperature below the cold unfolding the protein folds agai...

Proteins work only if folded in their native state, but changes in temperature T and pressure P induce their unfolding. Therefore for each protein there is a stability region (SR) in the T-P thermodynamic plane outside which the biomolecule is denaturated. It is known that the extension and shape of the SR depend on i) the specific protein residue-residue interactions in the native state of the amino acids sequence and ii) the water properties at the hydration interface. Here...

Experiments show that for many two state folders the free energy of the native state DG_ND([C]) changes linearly as the denaturant concentration [C] is varied. The slope, m = d DG_ND([C])/d[C], is nearly constant. The m-value is associated with the difference in the surface area between the native (N) and the denatured (D) state, which should be a function of DR_g^2, the difference in the square of the radius of gyration between the D and N states. Single molecule experiments...

First shells of hydration and bulk solvent plays a crucial role in the folding of proteins. Here, the role of water in the dynamics of proteins has been investigated using a theoretical protein-solvent model and a statistical physics approach. We formulate a hydration model where the hydrogen bonds between water molecules pertaining to the first shell of the protein conformation may be either mainly formed or broken. At thermal equilibrium, hydrogen bonds are formed at low te...

New experiments for water at the surface of proteins at very low temperature display intriguing dynamic behaviors. The extreme conditions of these experiments make it difficult to explore the wide range of thermodynamic state points needed to offer a suitable interpretation. Detailed simulations suffer the same problem, where equilibration times at low temperature become unreasonably long. We show how Monte Carlo simulations and mean field calculations of a tractable model of...

A large number of water models exists for molecular simulations. They differ in the ability to reproduce specific features of real water instead of others, like the correct temperature for the density maximum or the diffusion coefficient. Past analysis mostly concentrated on ensemble quantities, while few data was reported on the different microscopic behavior. Here, we compare seven widely used classical water models (SPC, SPC/E, TIP3P, TIP4P, TIP4P-Ew, TIP4P/2005 and TIP5P)...