Ribonucleic acid (RNA) of HIV-1 contains a 350 nucleotide, highly structured, cis-acting element called RRE (REV-response-element RNA), essential for virus replication. REV is a natural peptide that binds to RRE and transports it from the nucleus to cytoplasm where it is expressed into a new virus. The synthetic peptide known as RSG-1.2 also binds the RRE element and competes with REV. The purpose of study is to rationally design novel peptides such as RSG peptide with improved binding affinity to prevent the transport of HIV-1 RNA and so replication of virus. Herein, we performed MD simulation and free energy calculations to evaluate the interactions and binding free energies of REV (PDB ID: 4PMI) and RSGs peptides (PDB IDs: 1G70 and 1I9F) with RRE. The protein-RNA interactions were analyzed using the MM-PBSA method. Results suggest that REV has more binding free energy -188.41 kcal/mol than two RSG peptides with total binding free energy -120.97 and -141.46 kcal/mol. The ARG and ASN were found to be important residues of REV. In the RRE sequence, the nucleotides 62-67 and 78-84 were found to be important contributors in binding free energy. This study play a major role in elaboration of binding REV and RSG1-2 with RRE element and pave the way for further synthesis of peptide that can bind with RRE element and can be selected as therapeutic agent for HIV.Communicated by Ramaswamy H. Sarma.
Keywords: MM/PBSA: molecular dynamics; REV–RRE complex; polar solvation free energy.