mmCSM-AB: guiding rational antibody engineering through multiple point mutations.

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Myung, Yoochan 
Pires, Douglas EV 
Ascher, David B 

While antibodies are becoming an increasingly important therapeutic class, especially in personalized medicine, their development and optimization has been largely through experimental exploration. While there have been many efforts to develop computational tools to guide rational antibody engineering, most approaches are of limited accuracy when applied to antibody design, and have largely been limited to analysing a single point mutation at a time. To overcome this gap, we have curated a dataset of 242 experimentally determined changes in binding affinity upon multiple point mutations in antibody-target complexes (89 increasing and 153 decreasing binding affinity). Here, we have shown that by using our graph-based signatures and atomic interaction information, we can accurately analyse the consequence of multi-point mutations on antigen binding affinity. Our approach outperformed other available tools across cross-validation and two independent blind tests, achieving Pearson's correlations of up to 0.95. We have implemented our new approach, mmCSM-AB, as a web-server that can help guide the process of affinity maturation in antibody design. mmCSM-AB is freely available at

Antibodies, Antibody Affinity, Antigen-Antibody Complex, Point Mutation, Protein Engineering, Software
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Nucleic Acids Res
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Oxford University Press (OUP)
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Medical Research Council (MR/M026302/1)
Wellcome Trust (200814/Z/16/Z)
Y.M. was supported 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]; the Jack Brockhoff Foundation [JBF 4186, 2016]; Wellcome Trust [200814/Z/16/Z]; and an Investigator Grant from the National Health and Medical Research Council (NHMRC) of Australia [GNT1174405]. Supported in part by the Victorian Government’s OIS Program.