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mCSM-AB2: Guiding Rational Antibody Design Using Graph-Based Signatures

Accepted version
Peer-reviewed

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Type

Article

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Authors

Abstract

Motivation: A lack of accurate computational tools to guide rational mutagenesis has made affinity maturation a recurrent challenge in antibody development. We previously showed that graph-based signatures can be used to predict the effects of mutations on antibody 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 antibody-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, out-performing available methods currently used for rational antibody 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

Description

Keywords

Antibodies, Databases, Factual, Mutation, Software

Journal Title

Bioinformatics

Conference Name

Journal ISSN

1367-4803
1367-4811

Volume Title

36

Publisher

Oxford University Press

Rights

All rights reserved
Sponsorship
Medical Research Council (MR/M026302/1)
Y.M. and C.H.M.R were funded by the Melbourne Research Scholarship. D.B.A and D.E.V.P were funded by a Newton Fund RCUK-CONFAP Grant awarded by The Medical Research Council (MRC) and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) (MR/M026302/1), Conselho Nacional de Desenvolvimento Cientı́fico e Tecnológico (CNPq), the Jack Brockhoff Founda-tion (JBF 4186, 2016), and a C. J. Martin Research Fellowship from the National Health and Medical Research Council (NHMRC) of Australia (APP1072476). Supported in part by the Victorian Government’s OIS Program.