Effects of pressure on the structure of metmyoglobin: Molecular dynamics predictions for pressure unfolding through a molten globule intermediate

We investigated the pathway for pressure unfolding of metmyoglobin using molecular dynamics (MD) for a range of pressures (0.1 MPa to 1.2 GPa) and a temperature of 300 K. We find that the unfolding of metmyoglobin proceeds via a two-step mechanism native → molten globule intermediate → unfolded, where the molten globule forms at 700 MPa. The simulation describes qualitatively the experimental behavior of metmyoglobin under pressure. We find that unfolding of the alpha-helices follows the sequence of migrating hydrogen bonds (i,i + 4) → (i,i + 2).