Rigid-body docking with mutant constraints of influenza hemagglutinin with antibody HC19.
An automatic docking algorithm has been applied to the modeling of the complex between hemagglutinin from influenza virus and the Fab fragment of a monoclonal antibody raised against this antigen. We have introduced here the use of biochemical information provided by mutants of hemagglutinin. The docking procedure finds a small number of candidate solutions where three sites of escape mutations are buried and form hydrogen bonds in the interface. The localization of the epitope is improved by additional biochemical data about mutants that do not affect antibody binding. Five candidate solutions with low energy, reasonably well-packed interfaces, and six to ten hydrogen bonds are compatible with mutant information. One of the five stands out as generally better than the others from these points of views.
Cherfils
J
J
Laboratoire de Biologie Structurale, UMR 9920, CNRS-Université Paris Sud, Gil-sur-Yvette, France.
Bizebard
T
T
Knossow
M
M
Janin
J
J
D000465:Algorithms; D000595:Amino Acid Sequence; D000936:Antigen-Antibody Complex / Q000737:chemistry; D000937:Antigen-Antibody Reactions; D003198:Computer Simulation; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology; D006387:Hemagglutination, Viral / Q000187:drug effects; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D006860:Hydrogen Bonding; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D012641:Selection, Genetic
D000936:Antigen-Antibody Complex; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D007140:Immunoglobulin Fab Fragments