Computational epitope mapping of class I fusion proteins using Bayes classification [article]

Marion Frances Sauer Fischer, James E. Crowe, Jens Meiler
2022 bioRxiv   pre-print
Antibody epitope mapping of viral proteins plays a vital role in understanding immune system mechanisms of protection. In the case of class I viral fusion proteins, recent advances in cryo-electron microscopy and protein stabilization techniques have highlighted the importance of cryptic or 'alternative' conformations that expose epitopes targeted by potent neutralizing antibodies. Thorough epitope mapping of such metastable conformations is difficult, but is critical for understanding sites of
more » ... vulnerability in class I fusion proteins that occur as transient conformational states during viral attachment and fusion. We introduce a novel method Accelerated class I fusion protein Epitope Mapping (AxIEM) that accounts for fusion protein flexibility to significantly improve out-of-sample prediction of discontinuous antibody epitopes. Harnessing data from previous experimental epitope mapping efforts of several class I fusion proteins, we demonstrate that accuracy of epitope prediction depends on residue environment and allows for the precise prediction of conformation-dependent antibody target residues. We also show that AxIEM can to identify common epitopes and provide structural insights for the development and rational design of vaccines.
doi:10.1101/2022.05.23.493016 fatcat:4yg6u25gqvgvvojiq2pgjcuoee