All simulations were based on the crystal structure available from the laboratory of Alex Wlodawer at NCI. We initially performed simulations to assess the role of the crystal lattice on the position of the flap. A follow up study involved the suggestion that Zn ions block protease function. An experimental investigation by others had discovered that Zn(II) ions appeared to inhibit the HIV-1 protease dimer. We found by searching over an electrostatic grid,that Zn(II) ion was most likely located near the catalytic aspartates and that the ion remained essentially in the same position over a long simulation so as to block the expected normal enzymatic activity of the protease dimer. Several semiempirical quantum mechanical calculations were made on the local active site region to assess the role of H3O(+) and Zn(2+).
