A Computational Electrostatic Modeling Pipeline for Comparing pH-dependent gp120-CD4 Interactions in Founder and Chronic HIV Strains

Abstract

Though Human Immunodeficiency Virus has been studied for several decades, a consistently

effective vaccine has not yet been produced. While most experimental and computational

work in this area has been performed under slightly basic conditions (eg. blood/-

plasma), the viral transmission event generally occurs at the highly acidic mucosa. Since

pH can greatly affect protein structure, it likely affects epitope exposure to either inhibit or

facilitate transmission. In this thesis, a pipeline for analyzing the pH sensitivity of proteinprotein

interactions is applied to the transmission critical interaction between the HIV gp120

and host CD4 proteins. The interaction between gp120 and CD4 is shown to be stronger

at low pH for all strains tested, which is consistent with previous work and supports the

accuracy of the introduced pipeline. Also, early transmitted founder (TF) strains generally

bind CD4 better at low pH and are more pH sensitive than systemically circulating chronic

control (CC) strains.