Journal article

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

Yoochan Myung, Douglas E Pires, David B Ascher

NUCLEIC ACIDS RESEARCH | OXFORD UNIV PRESS | Published : 2020

Abstract

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..

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Grants

Awarded by Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG)


Awarded by Jack Brockhoff Foundation [JBF]


Awarded by Wellcome Trust


Awarded by National Health and Medical Research Council (NHMRC) of Australia


Funding Acknowledgements

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 Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) [MR/M026302/1]; the Jack Brockhoff Foundation [JBF 4186, 2016]; Wellcome Trust [200814/Z/16/Z]; Investigator Grant from the National Health and Medical Research Council (NHMRC) of Australia [GNT1174405]; Victorian Government's OIS Program (in part). Funding for open access charge: MRC. Conflict of interest statement. None declared.