MOLECULAR DYNAMICS SIMULATION OF HIV1 INTEGRASE INHIBITION FOR ELVITEGRAVIR, RALVITEGRAVIR AND DOLVITEGRAVIR: A MOLECULAR DAYNAMICS STUDY

Drug design for AIDS treatment via integrase inhibition is an area of great interest in biological research. Nevertheless, there are different hypotheses regarding the mechanism of integrase inhibitors of RAL, EVG and DTG, but few are well documented. In the present work we simulated PFV integrase with docked inhibitors using molecular dynamics method for 10 ns periods in order to understand the precise mechanism of action of studied inhibitors. Our results indicate that EVG displays a competitive-like kinetics of inhibition and tends to be of short-lasting and thus weak inhibitory effects, while DTG and RAL, being non-competitive inhibitors, interact more prominently with integrase. Our data also indicate that DTG and RAL reduce the total flexibility of the protein, especially at loop region and hence decrease its affinity for viral DNA. They may inhibit 3¢-OH processing activity of integrase as a necessary step before strand transfer. Therefore, chemicals such as DTG and RAL may provide good structural models for designing new integrase inhibitors of higher efficiency for AIDS treatment.