Free energy simulations of the HyHEL-10/HEL antibody-antigen complex.
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.
Pomès
R
R
Department of Chemistry, University of Houston, TX 77204, USA.
Willson
R C
RC
McCammon
J A
JA
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
D000936:Antigen-Antibody Complex; D007135:Immunoglobulin Variable Region; D014867:Water; D009113:Muramidase