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