COMPUTER MODELING OF ELECTROSTATIC STEERING AND ORIENTATIONAL EFFECTSIN ANTIBODY-ANTIGEN ASSOCIATION

Brownian dynamics simulations are performed to investigate the role of long-range electrostatic forces in the association of the monoclonal antibody HyHEL-5 with hen egg lysozyme. The electrostatic field of the antibody is obtained from a solution of the nonlinear Poisson-Boltzma nn using the x-ray crystal coordinates of this protein. The lysozyme i s represented as an asymmetric dumbbell consisting of two spheres of u nequal size, an arrangement that allows for the modeling of the orient ational requirements for docking. Calculations are done with the wild- type antibody and several point mutants at different ionic strengths. Changes in the charge distribution of the lysozyme are also considered . Results are compared with experiment and a simpler model in which th e lysozyme is approximated by a single charged sphere.