Résumé
Motivation: Cysteine residues have particular structural and functional relevance in proteins because of their ability to form covalent disulfide bonds. Bioinformatics tools that can accurately predict cysteine bonding states are already available, whereas it remains challenging to infer the disulfide connectivity pattern of unknown protein sequences. Improving accuracy in this area is highly relevant for the structural and functional annotation of proteins.
Results: We predict the intra-chain disulfide bond connectivity patterns starting from known cysteine bonding states with an evolutionary-based unsupervised approach called Sephiroth that relies on high-quality alignments obtained with HHblits and is based on a coarse-grained cluster-based modelization of tandem cysteine mutations within a protein family. We compared our method with state-of-the-art unsupervised predictors and achieve a performance improvement of 25-27% while requiring an order of magnitude less of aligned homologous sequences (similar to 10(3) instead of similar to 10(4)).