Microscopic Mechanism for Cold Denaturation

Abstract

We elucidate the mechanism of cold denaturation through constant-pressure simulations for a model of hydrophobic molecules in an explicit solvent. We find that the temperature dependence of the hydrophobic effect induces, facilitates, and is the driving force for cold denaturation. The physical mechanism underlying this phenomenon is identified as the destabilization of hydrophobic contact in favor of solvent-separated configurations, the same mechanism seen in pressure-induced denaturation. A phenomenological explanation proposed for the mechanism is suggested as being responsible for cold denaturation in real proteins.

Hydrophobic interactions in the formation of secondary structures in small peptides

“…Hydrophobic interactions are important in protein folding, denaturation [1][2][3][4], and packing. They are a major driving force for protein tertiary structure [5][6][7]; they can lead to non-native interactions during folding [8]; and they can affect the formation of α helices and β sheets [9] in proteins through packing [10] and local sterics [11].…”

A fully atomistic computer simulation study of cold denaturation of a β-hairpin

“…Unlike heat denaturation, whereby a native protein is disrupted at high temperature, cold denaturation is accompanied by decreases in both the system entropy and enthalpy. One possible explanation for this thermodynamic behaviour is a substantial ordering of water molecules around exposed hydrophobic residues and subsequent enhancement of the hydrogen bond network of shell water 1,2 . As the weakening hydrophobic force with decreasing temperature appears to be a key driving force governing cold denaturation, investigations of cold denaturation using either experimental or computational methods can provide new insights into the nature of hydrophobic effects.…”

“…Despite growing computational power and recent advances in simulation methods, all-atom MD studies directly targeting cold denaturation are rare. In fact, only a few computer simulations have been performed on this topic 2,7,9 . In earlier studies, a simple coarse-grained MD on a two-dimensional homopolymer model was applied in an effort to probe the microscopic origin of cold denaturation 2 .…”

“…In fact, only a few computer simulations have been performed on this topic 2,7,9 . In earlier studies, a simple coarse-grained MD on a two-dimensional homopolymer model was applied in an effort to probe the microscopic origin of cold denaturation 2 . Also, an enhanced MD incorporating generalized Born (GB) implicit solvation was employed to simulate the cold denaturation of a series of b-hairpin peptide models 7 .…”

Cutting Ice: Nanowire Regelation

“…Interactions between water molecules were described using the 3D Mercedes-Benz (MB) potential, a geometric water model designed to accurately reproduce the thermodynamic and structural properties of water, including freezing and pressure-induced melting, while being computationally more efficient than, e.g., the TIPnP models [20,21]. Although the extension of the MB model to 3D is relatively new [20], in 2D the MB model has been successful in describing the correct physics of phenomena such as cold denaturation of proteins [22], water's anomalous thermodynamic properties [23], and solute hydration [24]. The parameters of the potential were scaled so as to yield a melting temperature of approximately 270 K. The temperature range of 240-280 K was probed in the simulations, the presented results being obtained at 260 K. The wire was described in a coarse grained fashion as a rigid string of beads, where the beads interact with water molecules via hard-sphere pair potentials.…”