Some experiments of helical peptides indicate that the fraction of their helical structures increase under high-pressure conditions. Proteins are usually denatured under high pressure conditions, and therefore it is important to understand the molecular mechanism of pressure-induced structural changes of those helical peptides.
In this study, we chose two helical peptides whose fraction of helical structure increases with increasing pressure and examined the structural changes of these helical peptides by using molecular dynamics simulations. Molecular dynamics simulations often get trapped in the local minimum states of the free energy. To overcome such difficulty, the simulated tempering method for the isobaric-isothermal ensemble (Y. Mori and Y. Okamoto, J. Phys. Soc. Jpn. 79, 074003, 2010) was used for efficient sampling in pressure space.We performed molecular dynamics simulations with the simulated tempering method for the system of the two peptides in explicit water molecules. The simulation results suggest that the fraction of the helical structure of both peptides increases as pressure increases. We also calculated the free energy difference and the partial molar volume change as a function of pressure. The partial molar volume change from the helical state to the coil state increased monotonically from a negative value to a positive value with pressure. The positive value of the partial molar volume change at high pressure is consistent with the experimental results. Further structural analyses indicate that the helical structure of these peptides is squeezed when increasing pressure (Y. Mori and H. Okumura, J. Phys. Chem. Lett. 4, 2079, 2013).