mCSM-AB2: Guiding Rational Antibody Design

Yoochan Myung, Carlos H.M. Rodrigues, David B. Ascher, Douglas E. V. Pires

Abstract: Antibodies high specificity and affinity has led to their increasing therapeutic and diagnostic use. One challenge in antibody development has been affinity maturation, with a lack of accurate computational tools to guide rational mutagenesis.

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 1810 mutations with experimental binding measurements and structural information, mCSM-AB2 achieved a Pearson's correlation of 0.74 and 0.73 across training and blind tests, respectively, performing better than comparable methods that have been previously used for rational antibody engineering. The user-friendly and freely-accessible mCSM-AB2 webserver provides rapid analysis of both individual mutations or the entire interface to guide rational antibody affinity maturation