Mechanism of collagen folding propagation studied by Molecular Dynamics simulations.

Collagen forms a characteristic triple helical structure and plays a central role for stabilizing the extra-cellular matrix. After a C-terminal nucleus formation folding proceeds to form long triple-helical fibers. The molecular details of triple helix folding process is of central importance for an...

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Autores principales:	Julian Hartmann, Martin Zacharias
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/4fb9400c0f0248e59a0c184ad942ea78
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spelling	oai:doaj.org-article:4fb9400c0f0248e59a0c184ad942ea782021-11-25T05:40:37ZMechanism of collagen folding propagation studied by Molecular Dynamics simulations.1553-734X1553-735810.1371/journal.pcbi.1009079https://doaj.org/article/4fb9400c0f0248e59a0c184ad942ea782021-06-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1009079https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Collagen forms a characteristic triple helical structure and plays a central role for stabilizing the extra-cellular matrix. After a C-terminal nucleus formation folding proceeds to form long triple-helical fibers. The molecular details of triple helix folding process is of central importance for an understanding of several human diseases associated with misfolded or unstable collagen fibrils. However, the folding propagation is too rapid to be studied by experimental high resolution techniques. We employed multiple Molecular Dynamics simulations starting from unfolded peptides with an already formed nucleus to successfully follow the folding propagation in atomic detail. The triple helix folding was found to propagate involving first two chains forming a short transient template. Secondly, three residues of the third chain fold on this template with an overall mean propagation of ~75 ns per unit. The formation of loops with multiples of the repeating unit was found as a characteristic misfolding event especially when starting from an unstable nucleus. Central Gly→Ala or Gly→Thr substitutions resulted in reduced stability and folding rates due to structural deformations interfering with folding propagation.Julian HartmannMartin ZachariasPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 6, p e1009079 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Julian Hartmann Martin Zacharias Mechanism of collagen folding propagation studied by Molecular Dynamics simulations.
description	Collagen forms a characteristic triple helical structure and plays a central role for stabilizing the extra-cellular matrix. After a C-terminal nucleus formation folding proceeds to form long triple-helical fibers. The molecular details of triple helix folding process is of central importance for an understanding of several human diseases associated with misfolded or unstable collagen fibrils. However, the folding propagation is too rapid to be studied by experimental high resolution techniques. We employed multiple Molecular Dynamics simulations starting from unfolded peptides with an already formed nucleus to successfully follow the folding propagation in atomic detail. The triple helix folding was found to propagate involving first two chains forming a short transient template. Secondly, three residues of the third chain fold on this template with an overall mean propagation of ~75 ns per unit. The formation of loops with multiples of the repeating unit was found as a characteristic misfolding event especially when starting from an unstable nucleus. Central Gly→Ala or Gly→Thr substitutions resulted in reduced stability and folding rates due to structural deformations interfering with folding propagation.
format	article
author	Julian Hartmann Martin Zacharias
author_facet	Julian Hartmann Martin Zacharias
author_sort	Julian Hartmann
title	Mechanism of collagen folding propagation studied by Molecular Dynamics simulations.
title_short	Mechanism of collagen folding propagation studied by Molecular Dynamics simulations.
title_full	Mechanism of collagen folding propagation studied by Molecular Dynamics simulations.
title_fullStr	Mechanism of collagen folding propagation studied by Molecular Dynamics simulations.
title_full_unstemmed	Mechanism of collagen folding propagation studied by Molecular Dynamics simulations.
title_sort	mechanism of collagen folding propagation studied by molecular dynamics simulations.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/4fb9400c0f0248e59a0c184ad942ea78
work_keys_str_mv	AT julianhartmann mechanismofcollagenfoldingpropagationstudiedbymoleculardynamicssimulations AT martinzacharias mechanismofcollagenfoldingpropagationstudiedbymoleculardynamicssimulations
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Mechanism of collagen folding propagation studied by Molecular Dynamics simulations.

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