title: Rational engineering of a human anti-dengue antibody through experimentally validated computational docking.
abstract: Antibodies play an increasing pivotal role in both basic research and the biopharmaceutical sector, therefore technology for characterizing and improving their properties through rational engineering is desirable. This is a difficult task thought to require high-resolution x-ray structures, which are not always available. We, instead, use a combination of solution NMR epitope mapping and computational docking to investigate the structure of a human antibody in complex with the four Dengue virus serotypes. Analysis of the resulting models allows us to design several antibody mutants altering its properties in a predictable manner, changing its binding selectivity and ultimately improving its ability to neutralize the virus by up to 40 fold. The successful rational design of antibody mutants is a testament to the accuracy achievable by combining experimental NMR epitope mapping with computational docking and to the possibility of applying it to study antibody/pathogen interactions.
authors: Institute for Research in Biomedicine, Bellinzona, Switzerland.
authors: Luca
authors: L
authors: Simonelli
authors: Mattia
authors: M
authors: Pedotti
authors: Martina
authors: M
authors: Beltramello
authors: Elsa
authors: E
authors: Livoti
authors: Luigi
authors: L
authors: Calzolai
authors: Federica
authors: F
authors: Sallusto
authors: Antonio
authors: A
authors: Lanzavecchia
authors: Luca
authors: L
authors: Varani
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000914:Antibodies, Viral / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000936:Antigen-Antibody Complex; D001666:Binding Sites, Antibody; D017076:Computer-Aided Design; D003715:Dengue / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology*; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015202:Protein Engineering; D017386:Sequence Homology, Amino Acid; D020349:Surface Plasmon Resonance
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000936:Antigen-Antibody Complex; D000939:Epitopes