Pressure induced structural changes and dimer destabilization of HIV-1 protease studied by molecular dynamics simulations.

High-pressure methods have become attractive tools for investigation of the structural stability of proteins. Besides protein unfolding, dimerization can be studied this way, too. HIV-1 protease is a convenient target of experimental and theoretical high-pressure studies. In this study molecular-dynamics simulations are used to predict the response of HIV-1 protease to the pressure of 0.1 to 600 MPa. The protease conformation of both the monomer and the dimer is highly rigid changing insignificantly with growing pressure. Hydrophobicity of the protease decreases with increasing pressure. Water density inside the active-site cavity grows from 87% to 100% of the bulk water density within the pressure range. The dimer-dissociation volume change is negative for most of the pressure ranges with the minimum of -105 ml mol(-1), except for a short interval of positive values at low pressures. The dimer is thus slightly stabilized up to 160 MPa, but strongly destabilized by higher pressures.