Predictive analysis of structural interaction among HIV-1 proteins and Class I MHC molecule: A computational approach for therapeutic target

Abstract

Human immunodeficiency virus type 1 (HIV-1) remains a significant global health challenge because it can impair the host’s immune system and establish long-lasting infections. HIV-1 evades immune detection by modulating major histocompatibility complex class I (MHC-I) molecules, which are essential for presenting viral antigens to cytotoxic T lymphocytes (CTLs). The specific molecular interactions involved in this process remain unclear, which poses a challenge for the advancement of targeted therapies. In this study, we employed a systematic computational approach to explore the structural relationships between selected HIV-1 accessory proteins (nef, tat, rev,vpu) and human MHC-I molecules. Analyses included protein sequences evaluation to identify conserved domains and structural motifs, as well as prediction of secondary structures, transmembrane topology, and 3D-modelling for prediction of potential interaction sites. Structural alignments and molecular docking simulations demonstrated substantial conformational compatibility between HIV-1 proteins and MHC-I molecules, particularly in regions critical for immune modulation. The outcomes of this research provide novel insights into the structural mechanisms that underpin HIV-1-mediated immune evasion. This study identifies protein interfaces and conserved motifs related to MHC-I interference, providing insight for designing antiviral strategies to improve immune recognition and control viral persistence