A unified conformational selection and induced fit approach to protein-peptide docking.

Protein-peptide interactions are vital for the cell. They mediate, inhibit or serve as structural components in nearly 40% of all macromolecular interactions, and are often associated with diseases, making them interesting leads for protein drug design. In recent years, large-scale technologies have...

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Autores principales:	Mikael Trellet, Adrien S J Melquiond, Alexandre M J J Bonvin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/414b9492c08c4690aa9c30a537125667
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spelling	oai:doaj.org-article:414b9492c08c4690aa9c30a5371256672021-11-18T07:53:35ZA unified conformational selection and induced fit approach to protein-peptide docking.1932-620310.1371/journal.pone.0058769https://doaj.org/article/414b9492c08c4690aa9c30a5371256672013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23516555/?tool=EBIhttps://doaj.org/toc/1932-6203Protein-peptide interactions are vital for the cell. They mediate, inhibit or serve as structural components in nearly 40% of all macromolecular interactions, and are often associated with diseases, making them interesting leads for protein drug design. In recent years, large-scale technologies have enabled exhaustive studies on the peptide recognition preferences for a number of peptide-binding domain families. Yet, the paucity of data regarding their molecular binding mechanisms together with their inherent flexibility makes the structural prediction of protein-peptide interactions very challenging. This leaves flexible docking as one of the few amenable computational techniques to model these complexes. We present here an ensemble, flexible protein-peptide docking protocol that combines conformational selection and induced fit mechanisms. Starting from an ensemble of three peptide conformations (extended, a-helix, polyproline-II), flexible docking with HADDOCK generates 79.4% of high quality models for bound/unbound and 69.4% for unbound/unbound docking when tested against the largest protein-peptide complexes benchmark dataset available to date. Conformational selection at the rigid-body docking stage successfully recovers the most relevant conformation for a given protein-peptide complex and the subsequent flexible refinement further improves the interface by up to 4.5 Å interface RMSD. Cluster-based scoring of the models results in a selection of near-native solutions in the top three for ∼75% of the successfully predicted cases. This unified conformational selection and induced fit approach to protein-peptide docking should open the route to the modeling of challenging systems such as disorder-order transitions taking place upon binding, significantly expanding the applicability limit of biomolecular interaction modeling by docking.Mikael TrelletAdrien S J MelquiondAlexandre M J J BonvinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e58769 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mikael Trellet Adrien S J Melquiond Alexandre M J J Bonvin A unified conformational selection and induced fit approach to protein-peptide docking.
description	Protein-peptide interactions are vital for the cell. They mediate, inhibit or serve as structural components in nearly 40% of all macromolecular interactions, and are often associated with diseases, making them interesting leads for protein drug design. In recent years, large-scale technologies have enabled exhaustive studies on the peptide recognition preferences for a number of peptide-binding domain families. Yet, the paucity of data regarding their molecular binding mechanisms together with their inherent flexibility makes the structural prediction of protein-peptide interactions very challenging. This leaves flexible docking as one of the few amenable computational techniques to model these complexes. We present here an ensemble, flexible protein-peptide docking protocol that combines conformational selection and induced fit mechanisms. Starting from an ensemble of three peptide conformations (extended, a-helix, polyproline-II), flexible docking with HADDOCK generates 79.4% of high quality models for bound/unbound and 69.4% for unbound/unbound docking when tested against the largest protein-peptide complexes benchmark dataset available to date. Conformational selection at the rigid-body docking stage successfully recovers the most relevant conformation for a given protein-peptide complex and the subsequent flexible refinement further improves the interface by up to 4.5 Å interface RMSD. Cluster-based scoring of the models results in a selection of near-native solutions in the top three for ∼75% of the successfully predicted cases. This unified conformational selection and induced fit approach to protein-peptide docking should open the route to the modeling of challenging systems such as disorder-order transitions taking place upon binding, significantly expanding the applicability limit of biomolecular interaction modeling by docking.
format	article
author	Mikael Trellet Adrien S J Melquiond Alexandre M J J Bonvin
author_facet	Mikael Trellet Adrien S J Melquiond Alexandre M J J Bonvin
author_sort	Mikael Trellet
title	A unified conformational selection and induced fit approach to protein-peptide docking.
title_short	A unified conformational selection and induced fit approach to protein-peptide docking.
title_full	A unified conformational selection and induced fit approach to protein-peptide docking.
title_fullStr	A unified conformational selection and induced fit approach to protein-peptide docking.
title_full_unstemmed	A unified conformational selection and induced fit approach to protein-peptide docking.
title_sort	unified conformational selection and induced fit approach to protein-peptide docking.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/414b9492c08c4690aa9c30a537125667
work_keys_str_mv	AT mikaeltrellet aunifiedconformationalselectionandinducedfitapproachtoproteinpeptidedocking AT adriensjmelquiond aunifiedconformationalselectionandinducedfitapproachtoproteinpeptidedocking AT alexandremjjbonvin aunifiedconformationalselectionandinducedfitapproachtoproteinpeptidedocking AT mikaeltrellet unifiedconformationalselectionandinducedfitapproachtoproteinpeptidedocking AT adriensjmelquiond unifiedconformationalselectionandinducedfitapproachtoproteinpeptidedocking AT alexandremjjbonvin unifiedconformationalselectionandinducedfitapproachtoproteinpeptidedocking
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A unified conformational selection and induced fit approach to protein-peptide docking.

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