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.

SUBMITTER: Simonelli L 

PROVIDER: S-EPMC3566030 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature