Background Prediction of disulfide bridges from protein sequences is useful for characterizing structural and functional properties of proteins. Several methods based on different machine learning algorithms have been applied to solve this problem and public domain prediction services exist. These methods are however still potentially subject to significant improvements both in terms of prediction accuracy and overall architectural complexity. Results We introduce new methods for predicting disulfide bridges from protein sequences. The methods take advantage of two new decomposition kernels for measuring the similarity between protein sequences according to the amino acid environments around cysteines. Disulfide connectivity is predicted in two passes. First, a binary classifier is trained to predict whether a given protein chain has at least one intra-chain disulfide bridge. Second, a multiclass classifier (plemented by 1-nearest neighbor) is trained to predict connectivity patterns. The two passes can be easily cascaded to obtain connectivity prediction from sequence alone. We report an extensive experimental comparison on several data sets that have been previously employed in the literature to assess the accuracy of cysteine bonding state and disulfide connectivity predictors. Conclusion We reach state-of-the-art results on bonding state prediction with a simple method that classifies chains rather than individual residues. The prediction accuracy reached by our connectivity prediction method compares favorably with respect to all but the most complex other approaches. On the other hand, our method does not need any model selection or hyperparameter tuning, a property that makes it less prone to overfitting and prediction accuracy overestimation.
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