ROLE OF ELECTROSTATICS IN ANTIBODY-ANTIGEN ASSOCIATION - ANTI-HEN EGGLYSOZYME LYSOZYME COMPLEX (HYHEL-5 HEL)/

A recently developed multigrid-based Newton method for solving the non linear Poisson-Boltzmann equation is applied in an investigation of mo lecular recognition in the system consisting of the monoclonal antibod y HyHEL-5 and hen egg lysozyme. The electrostatic free energy of bindi ng is calculated for the wild-type complex and various mutants in whic h electrostatic interactions between the two proteins are altered. Mut ations which neutralize or reverse the charge of any of the residues i nvolved in salt-links in the native system always yield decreased bind ing affinities. The stability of the complex can be enhanced through t he formation of a newsalt-bridge obtained by mutating an asparagine re sidue of the lysozyme to the negatively-charged aspartate. Ionic stren gth effects are also examined and found to be significant in some case s.