TITLE

Rational Engineering of a Human Anti-Dengue Antibody through Experimentally Validated Computational Docking

AUTHOR(S)
Simonelli, Luca; Pedotti, Mattia; Beltramello, Martina; Livoti, Elsa; Calzolai, Luigi; Sallusto, Federica; Lanzavecchia, Antonio; Varani, Luca
PUB. DATE
February 2013
SOURCE
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
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.
ACCESSION #
87623842

 

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