In this study, we performed FMO calculations for the complexes of HIV-1 protease with 9 different inhibitors considering a protonation state observed experimentally for the active site amino acid residues Asp25(A, B) of HIV-1 protease and computed the inter-fragment interaction energies (IFIEs) between the inhibitor and the amino acid residues in HIV-1 protease. FMO computations show that sum of IFIEs for Ala28B, Asp29B, Asp30, and Gly49B can be strongly correlated to the dissociation constant, Kd value, of each inhibitor. We also found that these amino acid residues are located in the vicinity of parts of different structures and compositions in each inhibitor. Our results suggest that FMO calculations can be useful method to identify the amino acid residues important to activity relationship of HIV-1 protease.
