Analysis of the Interactions between the N-Terminal Peptide of gp41 and T20 Using Molecular Dynamics and Free Energy Calculations

T20 is the first fusion inhibitor, and it is allowed marketing approval from the FDA. Nevertheless, its application may be confined because of the high cost, virus resistance T20, and lack of oral availability. Therefore, it is necessary to develop more potent fusion inhibitor, and for this purpose, we analyzed the interactions between gp41 and T20. In that article, we have built three-dimensional model of the two peptide (the fusion peptide and the N-terminal heptad repeat of gp41, and T20) using the modeling and molecular dynamics (MD) simulation. The results were obtained Procheck program displays three-dimensional model were sufficiently accurate. By using docking and MD simulations, we verify that the three residues from the segment of LLSGIV in NHR of gp41 have large binding affinities with the T20. In addition we also verify the three residues from the lipid-binding domain of T20 have great binding free energy with the gp41. We wish that our results could be used to design more effective HIV-1 fusion inhibitors targeted to HIV-1 gp41.