A systematic framework for molecular dynamics simulations of protein post-translational modifications.

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 imp...

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Autores principales:	Drazen Petrov, Christian Margreitter, Melanie Grandits, Chris Oostenbrink, Bojan Zagrovic
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/88a20b43b01848c1ae196e353ff41b12
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spelling	oai:doaj.org-article:88a20b43b01848c1ae196e353ff41b122021-11-18T05:51:59ZA systematic framework for molecular dynamics simulations of protein post-translational modifications.1553-734X1553-735810.1371/journal.pcbi.1003154https://doaj.org/article/88a20b43b01848c1ae196e353ff41b122013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23874192/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358By 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.Drazen PetrovChristian MargreitterMelanie GranditsChris OostenbrinkBojan ZagrovicPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 9, Iss 7, p e1003154 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Drazen Petrov Christian Margreitter Melanie Grandits Chris Oostenbrink Bojan Zagrovic A systematic framework for molecular dynamics simulations of protein post-translational modifications.
description	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.
format	article
author	Drazen Petrov Christian Margreitter Melanie Grandits Chris Oostenbrink Bojan Zagrovic
author_facet	Drazen Petrov Christian Margreitter Melanie Grandits Chris Oostenbrink Bojan Zagrovic
author_sort	Drazen Petrov
title	A systematic framework for molecular dynamics simulations of protein post-translational modifications.
title_short	A systematic framework for molecular dynamics simulations of protein post-translational modifications.
title_full	A systematic framework for molecular dynamics simulations of protein post-translational modifications.
title_fullStr	A systematic framework for molecular dynamics simulations of protein post-translational modifications.
title_full_unstemmed	A systematic framework for molecular dynamics simulations of protein post-translational modifications.
title_sort	systematic framework for molecular dynamics simulations of protein post-translational modifications.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/88a20b43b01848c1ae196e353ff41b12
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A systematic framework for molecular dynamics simulations of protein post-translational modifications.

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