Prediction and validation of HIV-1 gp41 ecto-transmembrane domain post-fusion trimeric structure using molecular modeling

AbstractThe glycoproteins on the surface of human immunodeficiency virus (HIV) undergoes cascade of conformational transitions to evade the human immune system. The virus replicates inside the host and infects the T-cells instigating acquired immunodeficiency syndrome (AIDS). The glycoprotein 41 (gp41) of HIV helps to mediate the fusion of virus and host membranes. The detailed mechanism of host cell invasion by virus remains obscure due to the unavailability of experimental structure of complete gp41. In the current study, the post-fusion (PoF) trimeric structure of ecto-domain including transmembrane domain of gp41 was modeled using multiple homologous templates of Simian immunodeficiency virus (SIV) and HIV-1. In order to validate the gp41 model, interactions of three peptide inhibitors: T20, C37, and C34; were studied using all-atom molecular dynamics (MD) simulations, binding free energy calculation and per-residue energy decomposition analysis. The binding free energy calculated using MM-PBSA (Molec...