Large-Scale Prediction of Disulphide Bond Connectivity

The formation of disulphide bridges among cysteines is an important feature ofprotein structures. Here we develop new methods for the prediction ofdisulphide bond connectivity. We first build a large curated data set of proteins containing disulphide bridges and then use 2-Dimensional Recursive Neural Networks to predict bonding probabilities between cysteine pairs.These probabilities in turn lead to a weighted graph matching problem that can be addressed efficiently. We show how the method consistently achievesbetter results than previous approaches on the same validation data. In addition, the method can easily cope with chains with arbitrary numbers of bonded cysteines. Therefore, it overcomes one of the major limitations of previous approaches restricting predictions to chains containing no more than 10 oxidized cysteines. The method can be applied both to situations where the bonded state of each cysteine is known or unknown, in which case bonded state can be predicted with 85% precision and 90% recall. The method also yields an estimate for the total number of disulphide bridges in each chain.