title: Free energy simulations of the HyHEL-10/HEL antibody-antigen complex.
abstract: Free energy simulations are reported for the N31LD mutation, both in the HyHEL-10-HEL antibody-lysozyme complex and in the unliganded antibody, using the thermodynamic-cycle perturbation method. The present study suggests that the mutation would change the free energy of binding of the complex by -5.6 kcal/mol (unrestrained free energy simulations), by -0.5 kcal/mol (free energy simulations with a restrained backbone) and by 1.8 kcal/mol (Poisson-Boltzmann calculations, which also use a restrained geometry model). A detailed structural analysis helps in estimating the contributions from various residues and regions of the system. Enhanced recognition of HEL by the mutant HyHEL-10 would arise from the combination of thermodynamically more favorable conformational changes of the CDR loops upon association and subsequent charge pairing with Lys96 in the antigen.
authors.affiliation: Department of Chemistry, University of Houston, TX 77204, USA.
authors.forename: R
authors.initials: R
authors.lastname: Pomès
authors.forename: R C
authors.initials: RC
authors.lastname: Willson
authors.forename: J A
authors.initials: JA
authors.lastname: McCammon
mesh_terms: D000936:Antigen-Antibody Complex / Q000737:chemistry* / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000737:chemistry; D008956:Models, Chemical; D009113:Muramidase / Q000737:chemistry; D009154:Mutation; D016012:Poisson Distribution; D011487:Protein Conformation; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D000936:Antigen-Antibody Complex; D007135:Immunoglobulin Variable Region; D014867:Water; D009113:Muramidase