Role of electrostatics in antibody-antigen association: anti-hen egg lysozyme/lysozyme complex (HyHEL-5/HEL).

A recently developed multigrid-based Newton method for solving the nonlinear Poisson-Boltzmann equation is applied in an investigation of molecular recognition in the system consisting of the monoclonal antibody HyHEL-5 and hen egg lysozyme. The electrostatic free energy of binding is calculated for the wild-type complex and various mutants in which electrostatic interactions between the two proteins are altered. Mutations which neutralize or reverse the charge of any of the residues involved in salt-links in the native system always yield decreased binding affinities. The stability of the complex can be enhanced through the formation of a new salt-bridge obtained by mutating an asparagine residue of the lysozyme to the negatively-charged aspartate. Ionic strength effects are also examined and found to be significant in some cases.