ISulf-Cys: Prediction of S-sulfenylation Sites in Proteins with Physicochemical Properties of Amino Acids.

Yan Xu,Jun Ding,Ling-Yun Wu,Bin Liu

doi:10.1371/journal.pone.0154237

Abstract

Cysteine S-sulfenylation is an important post-translational modification (PTM) in proteins, and provides redox regulation of protein functions. Bioinformatics and structural analyses indicated that S-sulfenylation could impact many biological and functional categories and had distinct structural features. However, major limitations for identifying cysteine S-sulfenylation were expensive and low-throughout. In view of this situation, the establishment of a useful computational method and the development of an efficient predictor are highly desired. In this study, a predictor iSulf-Cys which incorporated 14 kinds of physicochemical properties of amino acids was proposed. With the 10-fold cross-validation, the value of area under the curve (AUC) was 0.7155 ± 0.0085, MCC 0.3122 ± 0.0144 on the training dataset for 20 times. iSulf-Cys also showed satisfying performance in the independent testing dataset with AUC 0.7343 and MCC 0.3315. Features which were constructed from physicochemical properties and position were carefully analyzed. Meanwhile, a user-friendly web-server for iSulf-Cys is accessible at http://app.aporc.org/iSulf-Cys/.

Highlights

Post-translational modifications (PTMs) play crucial roles in various cell functions and biological processes, as well as in regulating cellular plasticity and dynamics
It was discovered that the reversible S-sulfenylation modification was involved in various biological processing including cell signaling, response to stress, protein functions and signal transduction
The LOO always yielded a unique result for a given benchmark dataset and has been widely used in PTM sites [12,13,14,15,16] and various statistical predictors [17,18,19] because it was the most unbiased

Summary

Introduction

Post-translational modifications (PTMs) play crucial roles in various cell functions and biological processes, as well as in regulating cellular plasticity and dynamics. Cysteine S-sulfenylation in proteins, a reversible covalent oxidation, is one of the posttranslational modifications and has emerged as a dynamic mechanism for inactivation in protein family. It was discovered that the reversible S-sulfenylation modification was involved in various biological processing including cell signaling, response to stress, protein functions and signal transduction. Identifying S-sulfenylation modification with chemoproteomic approaches [1,2,3,4] have been developed and did not give specific modification sites. Increasing evidences have demonstrated that the site-specific mapping platform could find broad applications in chemical biology [5]. Yang [6] got over 1000 S-sulfenylation sites on more than 700 proteins through site-specific mapping. Experimental identification of S-sulfenylation sites with a site-

Methods

Results

Conclusion