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The conformational dynamics of HIV-1 protease (HIV-pr) is known to be essential for ligand binding and determination of cavity size, which changes with several common physiological parameters like temperature, pressure, pH conditions and of course the protein backbone mutations. In this work, the effect of pressure on the conformation and dynamics of HIV-pr was studied in silico at 1 bar (0.987 atm) and 3 Kbar pressure conditions. It can be seen from the literature that protein containing significant number of hydrophobic residues would expose its hydrophobic groups to the solvent exposed area under high pressure conditions, which eventually changes the dynamics and hence conformation of the protein. From our observations, the dynamics studies showed that, although the collective dynamics is restricted under pressure this is not true for some specific residues. From the secondary structure analysis it was observed that turns and bends are favored under high pressure at the expense of Â¿-helices and Ã-sheets resulting in the reduction of structural variability. Solvent accessible surface (SAS) area of both the low and high pressure simulations showed significant differences. It was also observed that with the elevation in pressure, the hydrophobic effect is decreased. All these conformational changes at high pressure condition may have a special impact on the binding affinity of drugs to the active site region, which may have a direct/indirect effect on the drug resistance behavior of HIV-pr.