Molecular Dynamic Simulation Studies on Cyclophilin- a Missing Cord in HIV-1 Capsid Assembly

Abstract The discovery of human Cyclophilin A (CyPA) inhibitor is of special interest in treating immunological disorders due to its characteristic protein iterative nature explicitly associated with its peptidyl-prolyl cis-trans isomerization activity. In this work,we have exemplified the significance of the Gly89-Pro90 peptide bond in the N-terminal domain of the capsid protein (CA). The Common Pharmacophore Hypothesis(CPH) AARR has been developed from PHASE, which has shown significant r 2 and q 2 values of 0.923and 0.631 respectively. Molecular docking studies reveal that Gln63, Arg55, Gly72 and Asn102 are the major hitpoints of HIV-1 Capsid His87Ala-Gly-Pro-Ile-Ala92 sequence preferably. Among the six active amino acids, Gly 89 and Pro 90 form major interactions with CyPA which is crucial for HIV-1 infection. This has been confirmed through mutating the respective Gly89 and Pro 90 with Aln (Alanine) residues. New molecules are screened virtually employing CPH template. Further the stability of the protein before and after the ligand binding is examined by molecular dynamics simulation studies using GROMACS. The analysis of RMSD curves and the number of hydrogen bonds are indicating that the ligand N7 (referred as ND1 in Graphical abstract) stably interact with the protein 2CYH with negligible fluctuations around the active site,