Prediction of disulfide bond engineering sites using a machine learning method

Disulfide bonds are covalently bonded sulfur atoms from cysteine pairs in protein structures. Due to the importance of disulfide bonds in protein folding and structural stability, artificial disulfide bonds are often engineered by cysteine mutation to enhance protein structural stability. To facilitate the experimental design, we implemented a method based on neural networks to predict amino acid pairs for cysteine mutations to form engineered disulfide bonds. The designed neural network was trained with high-resolution structures curated from the Protein Data Bank. The testing results reveal that the proposed method recognizes 99% of natural disulfide bonds. In the test with engineered disulfide bonds, the algorithm achieves similar accuracy levels with other state-of-the-art algorithms in published dataset and better performance for two comprehensively studied proteins with 70% accuracy, demonstrating potential applications in protein engineering. The neural network framework allows exploiting the full features in distance space, and therefore improves accuracy of the disulfide bond engineering site prediction. The source code and a web server are available at http://liulab.csrc.ac.cn/ssbondpre.