Abstract

Post-translational modifications (PTMs) occur in almost all proteins and play an important role in numerous biological processes by significantly affecting proteins' structure and dynamics. Several computational approaches have been developed to study PTMs (e.g., phosphorylation, sumoylation or palmitoylation) showing the importance of these techniques in predicting modified sites that can be further investigated with experimental approaches. In this review, we summarize some of the available online platforms and their contribution in the study of PTMs. Moreover, we discuss the emerging capabilities of molecular modeling and simulation that are able to complement these bioinformatics methods, providing deeper molecular insights into the biological function of post-translational modified proteins.

Highlights

  • Post-translational modifications (PTMs) occur on a large number of proteins de facto increasing the actual complexity of the proteome

  • It was observed that almost 5% of the human genome encodes enzymes in charge of catalyzing reactions leading to PTMs [8], highlighting once more the importance of these chemical modifications of the proteome

  • PTMs not induced by specific enzymes were observed to be responsible of non-specific protein damage involved in neurodegenerative diseases, cancer and diabetes [13,14,15]

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Summary

Introduction

Post-translational modifications (PTMs) occur on a large number of proteins de facto increasing the actual complexity of the proteome. Protein kinases can phosphorylate a given protein target to induce a signaling cascade, while this PTM can be further removed by specific protein phosphatases These enzymes are found in important signaling pathways, like G-protein [9,10] and Wnt signaling [11,12]. We provide an overview of some of the existing computational approaches used to study the most common PTMs, which we classified based on the covalent attachment of (i) small chemical groups, (ii) lipids or (iii) small proteins to the main peptide chain. Most of these tools are presented as online webservers, providing a user-friendly interface for PTM site identification. In this review we mainly focus our attention on this kind of resources, standalone software, like for instance PEAKS PTM [18], GlycoMaster [19] or MODa [20], are available but won't be covered here

Phosphorylation
Method
Method Information
Glycosylation
S-nitrosylation
Methylation
N-acetylation
Covalent attachment of acyl chains
Palmitoylation
N-myristoylation
Prenylation
Ubiquitylation
Sumoylation
PTMs cross-talk
Structural and dynamical characterization of PTMs
Findings
Summary and outlook
Full Text
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