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

We use systematic 8 ns ab initio molecular dynamics (AIMD) to study the structure and dynamics of water in bulk, and close to both hydrophobic and hydrophilic (carbonyl) groups of tetramethylurea (TMU). We observe crossovers in the dynamical behavior around the hydrophobic group at $T_X = 256 \pm 4$K and another one at $265 \pm 5$K related to the relative strength of water-water and water-carbonyl hydrogen bonds (HBs). For bulk water, the temperature of the apparent divergenc...

It has recently been shown that the TIP4P/Ice model of water can be studied numerically in metastable equilibrium at and below its liquid-liquid critical temperature. We report here simulations along a subcritical isotherm, for which two liquid states with the same pressure and temperature, but different density, can be equilibrated. This allows for a clear visualisation of the structural changes taking place across the transition. We specifically focus on how the topological...

The increase of aqueous solubility of nonpolar compounds upon cooling and the cold denaturation of proteins are established experimental facts. Both phenomena have been hypothesized to be related to restructuring of the hydrogen bond network of water around small nonpolar solutes or hydrophobic amino acid side chains. However, an underlying physical mechanism has yet to be identified. We assume the solute particles and the monomers of a polymer interact via a hard sphere pote...

Understanding how monomeric proteins fold under in vitro conditions is crucial to describing their functions in the cellular context. Significant advances both in theory and experiments have resulted in a conceptual framework for describing the folding mechanisms of globular proteins. The experimental data and theoretical methods have revealed the multifaceted character of proteins. Proteins exhibit universal features that can be determined using only the number of amino acid...

Studies of liquid water in its supercooled region have led to many insights into the structure and behavior of water. While bulk water freezes at its homogeneous nucleation temperature of approximately 235 K, for protein hydration water, the binding of water molecules to the protein avoids crystallization. Here we study the dynamics of the hydrogen bond (HB) network of a percolating layer of water molecules, comparing measurements of a hydrated globular protein with the resul...

Studying the properties of the solvent around proteins, we propose a much more sophisticated model of solvation than temperature-independent pairwise interactions between monomers, as is used commonly in lattice representations. We applied our model of solvation to a 16-monomer chain constrained on a two-dimensional lattice. We compute a phase diagram function of the temperature and a solvent parameter which is related to the pH of the solution. It exhibits a native state in ...

The hydrophobic effect stabilizes the native structure of proteins by minimizing the unfavourable interactions between hydrophobic residues and water through the formation of a hydrophobic core. Here we include the entropic and enthalpic contributions of the hydrophobic effect explicitly in an implicit solvent model. This allows us to capture two important effects: a length-scale dependence and a temperature dependence for the solvation of a hydrophobic particle. This consist...

We study the dynamics of hydration water/protein association in folded proteins, using lysozyme and myoglobin as examples. Extensive molecular dynamics simulations are performed to identify underlying mechanisms of the dynamical transition that corresponds to the onset of amplified atomic fluctuations in proteins. The number of water molecules within a cutoff distance of each residue scales linearly with protein depth index and is not affected by the local dynamics of the bac...

We present a computational study on the folding and aggregation of proteins in aqueous environment, as function of its concentration. We show how the increase of the concentration of individual protein species can induce a partial unfolding of the native conformation without the occurrence of aggregates. A further increment of the protein concentration results in the complete loss of the folded structures and induces the formation of protein aggregates. We discuss the effect ...

Comments: 6 pages RevTeX, 6 Postscript figures. We review a statistical mechanics treatment of the stability of globular proteins based on a simple model Hamiltonian taking into account protein self interactions and protein-water interactions. The model contains both hot and cold folding transitions. In addition it predicts a critical point at a given temperature and chemical potential of the surrounding water. The universality class of this critical point is new.