Calculation of binding energy using BLYP/MM for the HIV-1 integrase complexed with the S-1360 and two analogues Original Research Article

Integrase (IN) is one of the three human immunodeficiency virus type 1 (HIV-1) enzymes essential for effective viral replication. S-1360 is a potent and selective inhibitor of HIV-1 IN. In this work, we have carried out molecular dynamics (MD) simulations using a hybrid Quantum Mechanics/Molecular Mechanics (QM/MM) approach, to determine the protein–ligand interaction energy for S-1360 and two analogues. Analysis of the MD trajectories reveals that the strongest protein–inhibitor interactions, observed in the three studied complexes, are established with Lys-159 residue and Mg2+ cation. Calculations of binding energy using BLYP/MM level of theory reveal that there is a direct relationship between this theoretical computed property and the experimental determined anti-HIV activity.