Simulation of electrostatic effects in Fab-antigen complex formation.

ABSTRACT

A model based on the Poisson-Boltzmann equation has been used to model electrostatics in Anti-p24 (HIV-1) Fab-antigen association. The ionization state at different pH values has been simulated and the results have been used to estimate the stability at different pH values and to generate electrostatic potential maps at physiological ionic strength. The analysis of the electrostatic potential at the solvent-accessible surface shows that residues involved in binding are mostly found in the highest, but also in lowest potential regions. Brownian dynamics simulations have been used to estimate the enhancement of the association rate due to electrostatics which appears limited (approximately 2 at 150 mM ionic strength and approximately 3 at 15 mM ionic strength). A much more pronounced effect is observed upon increase of the charge of the diffusing particle. These results compare well with results obtained previously in similar studies on different systems and may serve to estimate the expected order of magnitude of electrostatic effects on association rates in antibody-antigen systems.