mCSM-AB2: guiding rational antibody design using graph-based signatures

Abstract Motivation A lack of accurate computational tools to guide rational mutagenesis has made affinity maturation a recurrent challenge in antibody (Ab) development. We previously showed that graph-based signatures can be used to predict the effects of mutations on Ab binding affinity. Results Here we present an updated and refined version of this approach, mCSM-AB2, capable of accurately modelling the effects of mutations on Ab–antigen binding affinity, through the inclusion of evolutionary and energetic terms. Using a new and expanded database of over 1800 mutations with experimental binding measurements and structural information, mCSM-AB2 achieved a Pearson’s correlation of 0.73 and 0.77 across training and blind tests, respectively, outperforming available methods currently used for rational Ab engineering. Availability and implementation mCSM-AB2 is available as a user-friendly and freely accessible web server providing rapid analysis of both individual mutations or the entire binding interface to guide rational antibody affinity maturation at http://biosig.unimelb.edu.au/mcsm_ab2 Supplementary information Supplementary data are available at Bioinformatics online.