Free energy simulations of the HyHEL-10/HEL antibody-antigen complex |
| |
| Authors: | Pomes, R. Willson, R.C. McCammon, J.A. |
| |
| Affiliation: | 1Department of Chemistry and Department of Biochemical and Biophysical Sciences, University of Houston Houston, TX 77204, USA 2Present address: Department of Chemistry, University of Montreal CP 6128, Succ. A, Montreal (Quebec) H3C 3J7, Canada 4Department of Chemical Engineering and Department of Biochemical and Biophysical Sciences, University of Houston Houston, TX 77204, USA 5Present address: Department of Chemistry and Biochemistry and Department of Pharmacology, University of California at San Diego La Jolla, CA 92093, USA |
| |
| Abstract: | Free energy simulations are reported for the N31L-D mutation,both in the HyHEL-10-HEL antibody-lysozyme complex and in theunliganded antibody, using the thermo-dynamic-cycle perturbationmethod. The present study suggests that the mutation would changethe 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 by1.8 kcal/ mol (Poisson-Boltzmann calculations, which also usea restrained geometry model). A detailed structural analysishelps in estimating the contributions from various residuesand regions of the system. Enhanced recognition of HEL by themutant HyHEL-10 would arise from the combination of thermodynamicallymore favorable conformational changes of the CDR loops uponassociation and subsequent charge pairing with Lys96 in theantigen. |
| |
| Keywords: | antibody-antigen complex/ free energy simulations/ single-point mutant/ thermodynamic cycle |
| 本文献已被 Oxford 等数据库收录！ |
|
