Simulation of electrostatic effects in Fab-antigen complex formation

A model based on the Poisson-Boltzmann equation has been used to model elec trostatics in Anti-p24 (HIV-1) Fab-antigen association. The ionization stat e at different pH values has been simulated and the results have been used to estimate the stability at different pH values and to generate electrosta tic potential maps at physiological ionic strength. The analysis of the ele ctrostatic potential at the solvent-accessible surface shows that residues involved in binding are mostly found in the highest, but also in lowest pot ential regions. Brownian dynamics simulations have been used to estimate th e enhancement of the association rate due to electrostatics which appears l imited (approximate to 2 at 150 mm ionic strength and approximate to 3 at 1 5 mm ionic strength). A much more pronounced effect is observed upon increa se of the charge of the diffusing particle. These results compare well with results obtained previously in similar studies on different systems and ma y serve to estimate the expected order of magnitude of electrostatic effect s on association rates in antibody-antigen systems.