Role of water in the pressure-induced unfolding of bovine pancreatic trypsin inhibitor (BPTI) protein: A molecular dynamics study

The mechanism of protein denaturation under pressure is still an active area of research. Using extensive molecular dynamics simulations, for a partially unfolded structures of BPTI protein, we have studied the role of water in the unfolding of proteins at pressures of 0.001, 5, and 10 kbar and 298K. Our results show that high enough pressure leads to insertion of water into the protein’s interior, causing structural perturbation to proteins, facilitated by a decrease in the intact time of intra-protein hydrogen bond acceptor-donor distances or an increase in the residence times of shell waters or by a combination of both.