Protein antigenicity: a thermodynamic approach.
This article summarizes computer-aided analyses of X-ray crystallographic data aimed at understanding the immunologically important aspects of the structure of antibody combining sites and protein antigens. In these calculations we use an empirical free energy potential function to estimate the atomic origin of binding specificity. By evaluating contributions of individual amino acid residues towards the Gibbs free energy of antibody-antigen complex formation, we arrive at a better understanding of the essential antigenic features of protein surfaces, as well as the inherent "binding" properties of the antibody combining sites. Such an "energetic" understanding of antigenicity may well be of practical importance in vaccine design. This article both reviews published data and discusses new results, i.e. delta G calculations on the HyHEL-10 complex with lysozyme, and an alternative treatment of the McPC 603 complex with phosphoryl choline.
Novotny
J
J
Bristol-Myers-Squibb Research Institute, Princeton, NJ 08543-4000.
D000936:Antigen-Antibody Complex / Q000737:chemistry*; D001666:Binding Sites, Antibody; D003196:Computer Graphics; D000939:Epitopes; D008958:Models, Molecular; D009113:Muramidase / Q000276:immunology; D011487:Protein Conformation; D011506:Proteins / Q000276:immunology*; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D000936:Antigen-Antibody Complex; D000939:Epitopes; D011506:Proteins; D009113:Muramidase