Vienna-PTM web server: a toolkit for MD simulations of protein post-translational modifications

Margreitter, Christian; Petrov, Dražen; Žagrović, Bojan

doi:10.1093/nar/gkt416

Cited by 143 publications

(110 citation statements)

References 37 publications

(41 reference statements)

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“…This should be contrasted with the above tools that provide parameters for isolated compounds only. Finally, in combination with a publicly available online tool for introducing PTMs of choice to a user-supplied protein 3D structure (Vienna-PTM server, http://vienna-ptm.univie.ac.at) [37], we provide a comprehensive, user-friendly toolkit for studying PTMs using MD simulations.…”

Section: Discussionmentioning

confidence: 99%

A Systematic Framework for Molecular Dynamics Simulations of Protein Post-Translational Modifications

et al. 2013

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By directly affecting structure, dynamics and interaction networks of their targets, post-translational modifications (PTMs) of proteins play a key role in different cellular processes ranging from enzymatic activation to regulation of signal transduction to cell-cycle control. Despite the great importance of understanding how PTMs affect proteins at the atomistic level, a systematic framework for treating post-translationally modified amino acids by molecular dynamics (MD) simulations, a premier high-resolution computational biology tool, has never been developed. Here, we report and validate force field parameters (GROMOS 45a3 and 54a7) required to run and analyze MD simulations of more than 250 different types of enzymatic and non-enzymatic PTMs. The newly developed GROMOS 54a7 parameters in particular exhibit near chemical accuracy in matching experimentally measured hydration free energies (RMSE = 4.2 kJ/mol over the validation set). Using this tool, we quantitatively show that the majority of PTMs greatly alter the hydrophobicity and other physico-chemical properties of target amino acids, with the extent of change in many cases being comparable to the complete range spanned by native amino acids.

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Section: Discussionmentioning

confidence: 99%

A Systematic Framework for Molecular Dynamics Simulations of Protein Post-Translational Modifications

et al. 2013

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“…For that purpose, ab initio quantum mechanics (QM) calculation, molecular mechanics (MM) or MD refinements, and experimental validation are all integrated (61). For example, a user-friendly and freely available platform for automated introduction of post-translocation modifications of choices to a protein 3D structure is presented by Vienna-PTM web server (http://viennaptm.univie.ac.at) (62). Furthermore, the ab initio QM/MM techniques have also been implemented to study histone modifying enzymes on their reaction mechanisms (63).…”

Section: Resultsmentioning

confidence: 99%

Computational Modeling to Elucidate Molecular Mechanisms of Epigenetic Memory

Xing

Jin

Zhang

et al. 2015

Epigenetic Technological Applications

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(100-250 words)How do mammalian cells that share the same genome exist in notably distinct phenotypes, exhibiting differences in morphology, gene expression patterns, and epigenetic chromatin statuses? Furthermore how do cells of different phenotypes differentiate reproducibly from a single fertilized egg? These are fundamental problems in developmental biology. Epigenetic histone modifications play an important role in the maintenance of different cell phenotypes. The exact molecular mechanism for inheritance of the modification patterns over cell generations remains elusive. The complexity comes partly from the number of molecular species and the broad time scales involved. In recent years mathematical modeling has made significant contributions on elucidating the molecular mechanisms of DNA methylation and histone Book chapter in Epigenetic Technological Applications (Elsevier), in press 2 covalent modification inheritance. We will pedagogically introduce the typical procedure and some technical details of performing a mathematical modeling study, and discuss future developments. Keywords (5-10)Histone epigenetic memory, mathematical modeling, reader and writer, pattern reconstruction, stochastic dynamics, histone modification enzyme, post-translational modification Outline:In this chapter we discuss how to use mathematical modeling to explore the dynamics and mechanism of histone modification dynamics. Book chapter inEpigenetic Technological Applications (Elsevier), in press 3 Textbody

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“…GROMACS have some limitations to parameterize phosphorylated residues in our protein structure. Thus, we amended the Gromos96 54a8 force field using Vienna‐PTM 2.0 program to recognize both phosphorylated and unphosphorylated residues with respect to our work . We added H atoms to our protein and centered in a cubic box by placing at 10 Å distance from the box edge and solvated with water .…”

Section: Methodsmentioning

confidence: 99%

Comparative analysis of human and mouse transcriptional cofactors (TcoFs) with special emphasis on intrinsically disordered regions and their associated regulating post‐translational modifications

Kamalesh

Sudandiradoss

2018

J of Cellular Biochemistry

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Drugs targeting transcriptional cofactors (TcoFs) function well in mouse models but fail to replicate their efficacy in human beings. Thus, we performed a comparative study on the TcoFs of humans and mice to find the similarity and dissimilarity between them. We observed high similarity in protein sequence and interacting domains between humans and mice. At the same time, dissimilarity was gradually increased in terms of interacting motifs, post-translational modifications, and molecular switches. Indeed, some of the post-translational modifications and molecular switches present in human beings are preferentially exempted in mice. Thus, structure-specific drugs designed to target TcoFs are functional in mice but fail in human beings, because the absence of some molecular switches in mice offers a particular conformation on the interacting motifs, which might facilitate drug binding. But in humans, owing to the presence of molecular switches, drug binding is not possible. From molecular dynamics simulation analysis, we inferred 8 different molecular switches on 3 proteins and found that 5 molecular switches influenced structural change in interacting motifs and revealed the reason for the functioning of drug in mice but not in human beings. From protein interaction network analysis, we find that a few interacting partners in mice are exempted in humans, and in both the cases the interacting partners are high when the domains are highly structured and the interacting partners are low when the domains are highly disordered. Hence, we are sure that our investigations will provide a promising support in future for designing drugs with high translational efficiency from mice models to human clinical trials.

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Vienna-PTM web server: a toolkit for MD simulations of protein post-translational modifications

Cited by 143 publications

References 37 publications

A Systematic Framework for Molecular Dynamics Simulations of Protein Post-Translational Modifications

A Systematic Framework for Molecular Dynamics Simulations of Protein Post-Translational Modifications

Computational Modeling to Elucidate Molecular Mechanisms of Epigenetic Memory

Comparative analysis of human and mouse transcriptional cofactors (TcoFs) with special emphasis on intrinsically disordered regions and their associated regulating post‐translational modifications

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