ICar-PseCp: identify carbonylation sites in proteins by Monte Carlo sampling and incorporating sequence coupled effects into general PseAAC.

Jianhua Jia,Zi Liu,Xuan Xiao,Kuo-Chen Chou,Bingxiang Liu

doi:10.18632/oncotarget.9148

Abstract

Carbonylation is a posttranslational modification (PTM or PTLM), where a carbonyl group is added to lysine (K), proline (P), arginine (R), and threonine (T) residue of a protein molecule. Carbonylation plays an important role in orchestrating various biological processes but it is also associated with many diseases such as diabetes, chronic lung disease, Parkinson's disease, Alzheimer's disease, chronic renal failure, and sepsis. Therefore, from the angles of both basic research and drug development, we are facing a challenging problem: for an uncharacterized protein sequence containing many residues of K, P, R, or T, which ones can be carbonylated, and which ones cannot? To address this problem, we have developed a predictor called iCar-PseCp by incorporating the sequence-coupled information into the general pseudo amino acid composition, and balancing out skewed training dataset by Monte Carlo sampling to expand positive subset. Rigorous target cross-validations on a same set of carbonylation-known proteins indicated that the new predictor remarkably outperformed its existing counterparts. For the convenience of most experimental scientists, a user-friendly web-server for iCar-PseCp has been established at http://www.jci-bioinfo.cn/iCar-PseCp, by which users can easily obtain their desired results without the need to go through the complicated mathematical equations involved. It has not escaped our notice that the formulation and approach presented here can also be used to analyze many other problems in computational proteomics.

Highlights

Cancer and many other major diseases are often caused by varieties of subtle modifications in biological sequences, typically by various types of post-translational modification (PTM or PTLM) in protein [1, 2], postreplication modification (PTRM) in DNA [3] and posttranscription modification (PTCM) in RNA [4]
Carbonylation plays an important role in orchestrating various biological processes but it is associated with many diseases such as diabetes, chronic lung disease, Parkinson’s disease, Alzheimer’s disease, chronic renal failure, and sepsis
Residues, of which 5 are predicted to be of carbonylation site and they are at the sequence positions 2, 14, 41, 68 and 95

Summary

Introduction

Cancer and many other major diseases are often caused by varieties of subtle modifications in biological sequences, typically by various types of post-translational modification (PTM or PTLM) in protein [1, 2], postreplication modification (PTRM) in DNA [3] and posttranscription modification (PTCM) in RNA [4]. When body’s well-designed proteolysis or other repair systems are overwhelmed by excess reactive oxygen species (ROS) [18], the oxidative stress may occur [18], weakening the damage-repairing ability. This may bring about varieties of PTMs on www.impactjournals.com/oncotarget proteins, including nitration, carbonylation, sulfhydration and glutathionylation [19]. Protein carbonylation is an early stage of diseases induced by external oxidative stress, aging and obesity [22, 23] It may cause numerous major human diseases, including Alzheimer’s disease, diabetes, Parkinson’s disease, chronic renal failure, chronic lung disease, sepsis and so forth [24, 25]. The information of carbonylation sites in proteins is indispensable for in-depth understanding many important biological processes and for precisely aiming targets in developing effective drugs against the aforementioned diseases

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Conclusion