On the temperature and pressure dependence of a range of properties of a type of water model commonly used in high-temperature protein unfolding simulations

ABSTRACT Molecular dynamics simulations of protein folding and unfolding are often carried out at temperatures (400–600 K) that are much higher than physiological or room temperature to speed up the (un)folding process. Use of such high temperatures changes both the protein and solvent properties considerably, compared to physiological or room temperature. Water models designed for use in conjunction with biomolecules, such as the simple point charge (SPC) model, have generally been calibrated at room temperature and pressure. To determine the distortive effect of high simulation tempera-tures on the behavior of such “room temperature ” water models, the structural, dynamic, and thermodynamic properties of the much-used SPC water model are investigated in the temperature range from 300 to 500 K. Both constant pressure and constant volume conditions, as used in protein simulations, were analyzed. We found that all properties analyzed change markedly with increasing temperature, but no phase transition in this temperature range was observed