In silico prediction and characterization of protein post-translational modifications

Gianazza, Elisabetta; Parravicini, Chiara; Primi, Roberto; Miller, Ingrid; Eberini, Ivano

doi:10.1016/j.jprot.2015.09.026

Cited by 12 publications

(9 citation statements)

References 122 publications

(111 reference statements)

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“…356 The main experimental method used for identification of protein modifications is mass spectroscopy, 355 but bioinformatics-based prediction tools are also quite successful and commonly used. 357 Most of the post-translational modifications are observed in all types of proteins in all cellular compartments; however, tyrosine sulfation occurs only in the transmembrane and secretory proteins. 358 Multiple types of post-translational modifications may take place on a given protein during various stages of its activity (a review summarizing the post-translational modifications in class-C GPCRs is given in ref (359), see Figure 12).…”

Section: Biomembranes As the Target Of Simulations: Native Membranes mentioning

confidence: 99%

Multiscale Simulations of Biological Membranes: The Challenge To Understand Biological Phenomena in a Living Substance

et al. 2019

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Biological membranes are tricky to investigate. They are complex in terms of molecular composition and structure, functional over a wide range of time scales, and characterized by nonequilibrium conditions. Because of all of these features, simulations are a great technique to study biomembrane behavior. A significant part of the functional processes in biological membranes takes place at the molecular level; thus computer simulations are the method of choice to explore how their properties emerge from specific molecular features and how the interplay among the numerous molecules gives rise to function over spatial and time scales larger than the molecular ones. In this review, we focus on this broad theme. We discuss the current state-of-the-art of biomembrane simulations that, until now, have largely focused on a rather narrow picture of the complexity of the membranes. Given this, we also discuss the challenges that we should unravel in the foreseeable future. Numerous features such as the actin-cytoskeleton network, the glycocalyx network, and nonequilibrium transport under ATP-driven conditions have so far received very little attention; however, the potential of simulations to solve them would be exceptionally high. A major milestone for this research would be that one day we could say that computer simulations genuinely research biological membranes, not just lipid bilayers.

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Section: Biomembranes As the Target Of Simulations: Native Membranes mentioning

confidence: 99%

Multiscale Simulations of Biological Membranes: The Challenge To Understand Biological Phenomena in a Living Substance

et al. 2019

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“…Many databases and prediction tools have been developed to enhance the understanding of various PTMs in different organisms and to simplify the analysis of complex PTM data (Gianazza et al 2016). These PTM databases contain crucial sequence annotations, specific to some PTM types and/or organisms (Gupta et al 1999;Hornbeck et al 2015;Yao and Xu 2017), and provide related structural data which mainly correspond to the mapping of the PTM sites in protein entries of the Protein Data Bank (PDB) (Huang et al 2016).…”

Section: In Context Of Protein Function This Diversity Leads To Coope...mentioning

confidence: 99%

Investigation of the impact of PTMs on the protein backbone conformation

et al. 2019

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Post-Translational Modifications (PTMs) are known to play a critical role in the regulation of the protein functions. Their impact on protein structures, and their link to disorder regions have already been spotted on the past decade. Nonetheless, the high diversity of PTMs types, and the multiple schemes of protein modifications (multiple PTMs, of different types, at different time, etc) make difficult the direct confrontation of PTM annotations and protein structures data.We so analyzed the impact of the residue modifications on the protein structures at local level. Thanks to a dedicated structure database, namely PTM-SD, a large screen of PTMs have been done and analyze at a local protein conformation levels using the structural alphabet Protein Blocks (PBs). We investigated the relation between PTMs and the backbone conformation of modified residues, of their local environment, and at the level of the complete protein structure. The two main PTM types (N-glycosylation and phosphorylation) have been studied in non-redundant datasets, and then, 4 different proteins were focused, covering 3 types of PTMs: N-glycosylation in renin endopeptidase and liver carboxylesterase, phosphorylation in cyclin-dependent kinase 2 (CDK2), and methylation in actin. We observed that PTMs could either stabilize or destabilize the backbone structure, at a local and global scale, and that these effects depend on the PTM types.

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“…Depending on the type, some PTMs appear to have a preference for being located in either ordered or disordered secondary structure elements. [46] While lysine acetylation has no apparent preference for secondary structure placement, serine/threonine/tyrosine phosphorylations were found to exhibit a preference for disordered regions. These secondary structure preferences were confirmed in this work for both of these respective PTMs (S8 Fig) . Location within disordered regions has been suggested to have certain advantages: it might allow for faster reactions, as well as easier recognition of PTM sites by modification enzymes.…”

Section: Plos Computational Biologymentioning

confidence: 99%

Molecular dynamics shows complex interplay and long-range effects of post-translational modifications in yeast protein interactions

Šoštarić

Noort

2021

PLoS Comput Biol

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Post-translational modifications (PTMs) play a vital, yet often overlooked role in the living cells through modulation of protein properties, such as localization and affinity towards their interactors, thereby enabling quick adaptation to changing environmental conditions. We have previously benchmarked a computational framework for the prediction of PTMs’ effects on the stability of protein-protein interactions, which has molecular dynamics simulations followed by free energy calculations at its core. In the present work, we apply this framework to publicly available data on Saccharomyces cerevisiae protein structures and PTM sites, identified in both normal and stress conditions. We predict proteome-wide effects of acetylations and phosphorylations on protein-protein interactions and find that acetylations more frequently have locally stabilizing roles in protein interactions, while the opposite is true for phosphorylations. However, the overall impact of PTMs on protein-protein interactions is more complex than a simple sum of local changes caused by the introduction of PTMs and adds to our understanding of PTM cross-talk. We further use the obtained data to calculate the conformational changes brought about by PTMs. Finally, conservation of the analyzed PTM residues in orthologues shows that some predictions for yeast proteins will be mirrored to other organisms, including human. This work, therefore, contributes to our overall understanding of the modulation of the cellular protein interaction networks in yeast and beyond.

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In silico prediction and characterization of protein post-translational modifications

Cited by 12 publications

References 122 publications

Multiscale Simulations of Biological Membranes: The Challenge To Understand Biological Phenomena in a Living Substance

Multiscale Simulations of Biological Membranes: The Challenge To Understand Biological Phenomena in a Living Substance

Investigation of the impact of PTMs on the protein backbone conformation

Molecular dynamics shows complex interplay and long-range effects of post-translational modifications in yeast protein interactions

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