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Quaternary structure predictions of transmembrane proteins starting from the monomer: a docking-based approach

BACKGROUND: We introduce a computational protocol for effective predictions of the supramolecular organization of integral transmembrane proteins, starting from the monomer. Despite the demonstrated constitutive and functional importance of supramolecular assemblies of transmembrane subunits or prot...

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Detalles Bibliográficos
Autores principales: Casciari, D, Seeber, M, Fanelli, F
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1590055/
https://www.ncbi.nlm.nih.gov/pubmed/16836758
http://dx.doi.org/10.1186/1471-2105-7-340
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author Casciari, D
Seeber, M
Fanelli, F
author_facet Casciari, D
Seeber, M
Fanelli, F
author_sort Casciari, D
collection PubMed
description BACKGROUND: We introduce a computational protocol for effective predictions of the supramolecular organization of integral transmembrane proteins, starting from the monomer. Despite the demonstrated constitutive and functional importance of supramolecular assemblies of transmembrane subunits or proteins, effective tools for structure predictions of such assemblies are still lacking. Our computational approach consists in rigid-body docking samplings, starting from the docking of two identical copies of a given monomer. Each docking run is followed by membrane topology filtering and cluster analysis. Prediction of the native oligomer is therefore accomplished by a number of progressive growing steps, each made of one docking run, filtering and cluster analysis. With this approach, knowledge about the oligomerization status of the protein is required neither for improving sampling nor for the filtering step. Furthermore, there are no size-limitations in the systems under study, which are not limited to the transmembrane domains but include also the water-soluble portions. RESULTS: Benchmarks of the approach were done on ten homo-oligomeric membrane proteins with known quaternary structure. For all these systems, predictions led to native-like quaternary structures, i.e. with C(α)-RMSDs lower than 2.5 Å from the native oligomer, regardless of the resolution of the structural models. CONCLUSION: Collectively, the results of this study emphasize the effectiveness of the prediction protocol that will be extensively challenged in quaternary structure predictions of other integral membrane proteins.
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spelling pubmed-15900552006-10-05 Quaternary structure predictions of transmembrane proteins starting from the monomer: a docking-based approach Casciari, D Seeber, M Fanelli, F BMC Bioinformatics Methodology Article BACKGROUND: We introduce a computational protocol for effective predictions of the supramolecular organization of integral transmembrane proteins, starting from the monomer. Despite the demonstrated constitutive and functional importance of supramolecular assemblies of transmembrane subunits or proteins, effective tools for structure predictions of such assemblies are still lacking. Our computational approach consists in rigid-body docking samplings, starting from the docking of two identical copies of a given monomer. Each docking run is followed by membrane topology filtering and cluster analysis. Prediction of the native oligomer is therefore accomplished by a number of progressive growing steps, each made of one docking run, filtering and cluster analysis. With this approach, knowledge about the oligomerization status of the protein is required neither for improving sampling nor for the filtering step. Furthermore, there are no size-limitations in the systems under study, which are not limited to the transmembrane domains but include also the water-soluble portions. RESULTS: Benchmarks of the approach were done on ten homo-oligomeric membrane proteins with known quaternary structure. For all these systems, predictions led to native-like quaternary structures, i.e. with C(α)-RMSDs lower than 2.5 Å from the native oligomer, regardless of the resolution of the structural models. CONCLUSION: Collectively, the results of this study emphasize the effectiveness of the prediction protocol that will be extensively challenged in quaternary structure predictions of other integral membrane proteins. BioMed Central 2006-07-12 /pmc/articles/PMC1590055/ /pubmed/16836758 http://dx.doi.org/10.1186/1471-2105-7-340 Text en Copyright © 2006 Casciari et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Methodology Article
Casciari, D
Seeber, M
Fanelli, F
Quaternary structure predictions of transmembrane proteins starting from the monomer: a docking-based approach
title Quaternary structure predictions of transmembrane proteins starting from the monomer: a docking-based approach
title_full Quaternary structure predictions of transmembrane proteins starting from the monomer: a docking-based approach
title_fullStr Quaternary structure predictions of transmembrane proteins starting from the monomer: a docking-based approach
title_full_unstemmed Quaternary structure predictions of transmembrane proteins starting from the monomer: a docking-based approach
title_short Quaternary structure predictions of transmembrane proteins starting from the monomer: a docking-based approach
title_sort quaternary structure predictions of transmembrane proteins starting from the monomer: a docking-based approach
topic Methodology Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1590055/
https://www.ncbi.nlm.nih.gov/pubmed/16836758
http://dx.doi.org/10.1186/1471-2105-7-340
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