Simonelli, Luca Pedotti, Mattia Beltramello, Martina Livoti, Elsa Calzolai, Luigi Sallusto, Federica Lanzavecchia, Antonio Varani, Luca 2013-02-06 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. application/pdf https://susi.usi.ch/global/documents/319180 https://localhost:5000/ark:/12658/srd1319180 https://susi.usi.ch/documents/319180/files/Simonelli_PO_2013.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0055561 info:eu-repo/semantics/altIdentifier/ark/12658/srd1319180 info:eu-repo/semantics/openAccess CC BY Plos one. - 2013, vol. 8, no. 2, p. e55561 info:eu-repo/classification/udc/61 Rational engineering of a human anti-dengue antibody through experimentally validated computational docking http://purl.org/coar/resource_type/c_6501