Rosetta FlexPepDock ab-initio: simultaneous folding, docking and refinement of peptides onto their receptors.

Flexible peptides that fold upon binding to another protein molecule mediate a large number of regulatory interactions in the living cell and may provide highly specific recognition modules. We present Rosetta FlexPepDock ab-initio, a protocol for simultaneous docking and de-novo folding of peptides...

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Autores principales:	Barak Raveh, Nir London, Lior Zimmerman, Ora Schueler-Furman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ba64ffc8d22344e9bef42e750d34b527
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spelling	oai:doaj.org-article:ba64ffc8d22344e9bef42e750d34b5272021-11-18T06:54:35ZRosetta FlexPepDock ab-initio: simultaneous folding, docking and refinement of peptides onto their receptors.1932-620310.1371/journal.pone.0018934https://doaj.org/article/ba64ffc8d22344e9bef42e750d34b5272011-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21572516/?tool=EBIhttps://doaj.org/toc/1932-6203Flexible peptides that fold upon binding to another protein molecule mediate a large number of regulatory interactions in the living cell and may provide highly specific recognition modules. We present Rosetta FlexPepDock ab-initio, a protocol for simultaneous docking and de-novo folding of peptides, starting from an approximate specification of the peptide binding site. Using the Rosetta fragments library and a coarse-grained structural representation of the peptide and the receptor, FlexPepDock ab-initio samples efficiently and simultaneously the space of possible peptide backbone conformations and rigid-body orientations over the receptor surface of a given binding site. The subsequent all-atom refinement of the coarse-grained models includes full side-chain modeling of both the receptor and the peptide, resulting in high-resolution models in which key side-chain interactions are recapitulated. The protocol was applied to a benchmark in which peptides were modeled over receptors in either their bound backbone conformations or in their free, unbound form. Near-native peptide conformations were identified in 18/26 of the bound cases and 7/14 of the unbound cases. The protocol performs well on peptides from various classes of secondary structures, including coiled peptides with unusual turns and kinks. The results presented here significantly extend the scope of state-of-the-art methods for high-resolution peptide modeling, which can now be applied to a wide variety of peptide-protein interactions where no prior information about the peptide backbone conformation is available, enabling detailed structure-based studies and manipulation of those interactions.Barak RavehNir LondonLior ZimmermanOra Schueler-FurmanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 4, p e18934 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Barak Raveh Nir London Lior Zimmerman Ora Schueler-Furman Rosetta FlexPepDock ab-initio: simultaneous folding, docking and refinement of peptides onto their receptors.
description	Flexible peptides that fold upon binding to another protein molecule mediate a large number of regulatory interactions in the living cell and may provide highly specific recognition modules. We present Rosetta FlexPepDock ab-initio, a protocol for simultaneous docking and de-novo folding of peptides, starting from an approximate specification of the peptide binding site. Using the Rosetta fragments library and a coarse-grained structural representation of the peptide and the receptor, FlexPepDock ab-initio samples efficiently and simultaneously the space of possible peptide backbone conformations and rigid-body orientations over the receptor surface of a given binding site. The subsequent all-atom refinement of the coarse-grained models includes full side-chain modeling of both the receptor and the peptide, resulting in high-resolution models in which key side-chain interactions are recapitulated. The protocol was applied to a benchmark in which peptides were modeled over receptors in either their bound backbone conformations or in their free, unbound form. Near-native peptide conformations were identified in 18/26 of the bound cases and 7/14 of the unbound cases. The protocol performs well on peptides from various classes of secondary structures, including coiled peptides with unusual turns and kinks. The results presented here significantly extend the scope of state-of-the-art methods for high-resolution peptide modeling, which can now be applied to a wide variety of peptide-protein interactions where no prior information about the peptide backbone conformation is available, enabling detailed structure-based studies and manipulation of those interactions.
format	article
author	Barak Raveh Nir London Lior Zimmerman Ora Schueler-Furman
author_facet	Barak Raveh Nir London Lior Zimmerman Ora Schueler-Furman
author_sort	Barak Raveh
title	Rosetta FlexPepDock ab-initio: simultaneous folding, docking and refinement of peptides onto their receptors.
title_short	Rosetta FlexPepDock ab-initio: simultaneous folding, docking and refinement of peptides onto their receptors.
title_full	Rosetta FlexPepDock ab-initio: simultaneous folding, docking and refinement of peptides onto their receptors.
title_fullStr	Rosetta FlexPepDock ab-initio: simultaneous folding, docking and refinement of peptides onto their receptors.
title_full_unstemmed	Rosetta FlexPepDock ab-initio: simultaneous folding, docking and refinement of peptides onto their receptors.
title_sort	rosetta flexpepdock ab-initio: simultaneous folding, docking and refinement of peptides onto their receptors.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/ba64ffc8d22344e9bef42e750d34b527
work_keys_str_mv	AT barakraveh rosettaflexpepdockabinitiosimultaneousfoldingdockingandrefinementofpeptidesontotheirreceptors AT nirlondon rosettaflexpepdockabinitiosimultaneousfoldingdockingandrefinementofpeptidesontotheirreceptors AT liorzimmerman rosettaflexpepdockabinitiosimultaneousfoldingdockingandrefinementofpeptidesontotheirreceptors AT oraschuelerfurman rosettaflexpepdockabinitiosimultaneousfoldingdockingandrefinementofpeptidesontotheirreceptors
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Rosetta FlexPepDock ab-initio: simultaneous folding, docking and refinement of peptides onto their receptors.

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