  Hydrostatic pressure is a common perturbation to probe the conformations of
proteins. There are two common forms of pressure dependent potentials of mean
force (PMFs) derived from hydrophobic molecules available for the coarse
grained molecular simulations of protein folding and unfolding under
hydrostatic pressure. Although both PMF includes a desolvation barrier
separating the well of a direct contact and the well of a solvent mediated
contact, how these features vary with hydrostatic pressure is still debated.
There is a need of a systematic comparison of these two PMFs on a protein. We
investigated the two different pressure dependencies on the desolvation
potential in a structure based protein model using coarse grained molecular
simulations. We compared them to the known behavior a real protein based on
experimental evidence. We showed that the protein s folding transition curve on
the pressure temperature phase diagram depends on the relationship between the
potential well minima and pressure. For protein that reduces the total volume
under pressure, it is essential for the PMF to carry the feature that the
direct contact well is essential less stable than the water mediated contact
well at high pressure. We also comment on the practicality and importance of
structure based minimalist models for understanding the phenomenological
behavior of a protein under a wide range of phase space.
