The Molecular Basis of pH-Modulated HIV gp120 Binding Revealed

Abstract

Decades of research has yet to provide a vaccine for HIV, the virus which causes AIDS. Recent theoretical research has turned attention to mucosa pH levels over systemic pH levels. Previous research in this field developed a computational approach for determining pH sensitivity that indicated higher potential for transmission at mucosa pH levels present during intercourse. The process was extended to incorporate a principal component analysis (PCA)-based machine learning technique for classification of gp120 proteins against a known transmitted variant called Biomolecular Electro-Static Indexing (BESI). The original process has since been extended to the residue level by a process we termed Electrostatic Variance Masking (EVM) and used in conjunction with BESI to determine structural differences present among various subspecies across Clades A1 and C. Results indicate that structures outside of the core selected by EVM may be responsible for binding affinity observed in many other studies and that pH modulation of select substructures indicated by EVM may influence specific regions of the viral envelope protein (Env) involved in protein-protein interactions.