Litchi chinensis-derived terpenoid as anti-HIV-1 protease agent: structural design from molecular dynamics simulations

The molecular structures of the binding between human immunodeficiency virus-1 protease (HIV-1PR) and various inhibitors including existing extensive natural products extracts have been investigated for anti-HIV drug development. In this study, the binding of HIV-1PR and a terpenoid from Litchi chinensis extracts (3-oxotrirucalla-7,24-dien-21-oic acid) was investigated in order to clarify the inhibition effectiveness of this compound. Molecular dynamics (MD) simulations of HIV-1PR complex with 3-oxotrirucalla-7,24-dien-21-oic acid were performed including water molecules. The MD simulation results indicated the formation of hydrogen bonds between the oxygen atoms of the inhibitor and the catalytic aspartates, which are commonly found in inhibitors–protease complexes. On the other hand, no hydrogen bonding of this particular inhibitor to the flap region was found. In addition, the radial distribution function of water oxygens around the catalytic carboxylate nitrogens of Asp29 and Asp30 suggests that at least one or two water molecules are in the active site region whereas direct interaction of the inhibitor was found for catalytic carboxylate oxygen of Asp25. The results of this simulation, in comparison with the structures of other HIV-PR inhibitor complexes, could lead to a better understanding of the activity of 3-oxotrirucalla-7,24-dien-21-oic acid.