MOLECULAR MODELLING OF HIV-1 DRUG RESISTANT MUTANTS WITH REFERENCE TO WILD TYPE

摘要

Drug resistance mutations M184V and M184I are associated with lamivudine. Y181C and H221Y drug resistance mutations are associated with nevirapine and efavirenz and G190R and M230I drug resistance mutations are associated with efavirenz in the reverse transcriptase gene of HIV-1. In the present study, we attempted to identify the drug resistance mutations and interacting amino acids in the reverse transcriptase gene of HIV-1 through a molecular docking approach. Molecular docking of first-line antiretroviral drugs like lamivudine, nevirapine, and efavirenz with wild and mutant type structures was performed using MTi auto dock to compare the binding behaviour of drugs with amino acids of the reverse transcriptase gene. The receptor structure preparation was performed by the University of California, San Francisco chimera (UCSF Chimera). The Ligplot program was used to plot the 2D interaction diagrams of protein-ligand complexes. The 3D models of the mutant-drugs were generated using PyMOL (PyMOL molecular graphics system). The clear bond interactions were visualized with Discovery Studio 3.5 (BIOVIA, USA). Thus, these findings suggest that mutations in the reverse transcriptase gene, thereby leading to drug resistance in HIV-1 infected patients due to the incompetent binding of the drugs.