Free energy simulations of the HyHEL-10/HEL antibody-antigen complex

R. Pomès, R. C. Willson, J. A. Mccammon

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Free energy simulations are reported for the N31(L)D 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.

Original languageEnglish (US)
Pages (from-to)663-675
Number of pages13
JournalProtein Engineering, Design and Selection
Issue number7
StatePublished - Jul 1995


  • Antibody-antigen complex
  • Free energy simulations
  • Single-point mutant
  • Thermodynamic cycle

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Pharmacology
  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Bioengineering
  • Biotechnology


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