Reversible Temperature and Pressure Denaturation of a Protein Fragment: A Replica Exchange Molecular Dynamics Simulation Study

We determine the reversible folding-unfolding of the C-terminal (41–56) fragment of protein G as a function of density and temperature using replica exchange molecular dynamics simulations. We employ a total of 253 replicas, covering the temperature range between 320 and 515 K and the density range between $0.96$ and $1.16\mathrm{g}{\mathrm{c}\mathrm{m}}^{-3}$. Using the root mean square deviation from the folded structure as a quantitative measure, we are able to obtain the fraction of folded states, and can thus establish the free energy difference between the folded and the unfolded states of the protein fragment as a function of temperature and pressure. For the pressure denaturation the weakening of the hydrophobic interaction between the bulky side chains is found to be crucial at lower temperatures, leading to an apparent destabilization of the folded backbone structure at elevated pressures.