pH Dependent Binding Energies of Broadly Neutralizing Antibodies

Understanding how pH modulates underlying protein-protein interaction requires in-depth analysis across combinations of HIV proteins and broadly neutralizing antibodies (bnAbs). Traditional labs are not practical to screen all sequence variations and titrate of pH, highlighting the need to analyze such interactions theoretically. To fill this need, we generate homology models of predetermined HIV-1 gp120 in complex with bnAbs, through computational simulations to observe the binding energies as environmental pH varies. We compare simulation data to experimental data of the same structures at pH 5.5 and pH 7.4 specifically to present an 83.3% agreement between the two approaches to support the hypothesis that binding is stronger at lower pH. We then make observations of binding energy predictions across broad spectrum pH to provide insight into factors limiting the effectiveness of bnAbs in vivo. We conclude that theoretical models, and simulations involving them, provide data that closely mimic those of laboratory results.