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Analysis of Protein Disorder Predictions in the Light of a Protein Structural Alphabet

Intrinsically-disordered protein (IDP) characterization was an amazing change of paradigm in our classical sequence-structure-function theory. Moreover, IDPs are over-represented in major disease pathways and are now often targeted using small molecules for therapeutic purposes. This has had created...

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Autor principal: de Brevern, Alexandre G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408373/
https://www.ncbi.nlm.nih.gov/pubmed/32698546
http://dx.doi.org/10.3390/biom10071080
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author de Brevern, Alexandre G.
author_facet de Brevern, Alexandre G.
author_sort de Brevern, Alexandre G.
collection PubMed
description Intrinsically-disordered protein (IDP) characterization was an amazing change of paradigm in our classical sequence-structure-function theory. Moreover, IDPs are over-represented in major disease pathways and are now often targeted using small molecules for therapeutic purposes. This has had created a complex continuum from order-that encompasses rigid and flexible regions-to disorder regions; the latter being not accessible through classical crystallographic methodologies. In X-ray structures, the notion of order is dictated by access to resolved atom positions, providing rigidity and flexibility information with low and high experimental B-factors, while disorder is associated with the missing (non-resolved) residues. Nonetheless, some rigid regions can be found in disorder regions. Using ensembles of IDPs, their local conformations were analyzed in the light of a structural alphabet. An entropy index derived from this structural alphabet allowed us to propose a continuum of states from rigidity to flexibility and finally disorder. In this study, the analysis was extended to comparing these results to disorder predictions, underlying a limited correlation, and so opening new ideas to characterize and predict disorder.
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spelling pubmed-74083732020-08-13 Analysis of Protein Disorder Predictions in the Light of a Protein Structural Alphabet de Brevern, Alexandre G. Biomolecules Communication Intrinsically-disordered protein (IDP) characterization was an amazing change of paradigm in our classical sequence-structure-function theory. Moreover, IDPs are over-represented in major disease pathways and are now often targeted using small molecules for therapeutic purposes. This has had created a complex continuum from order-that encompasses rigid and flexible regions-to disorder regions; the latter being not accessible through classical crystallographic methodologies. In X-ray structures, the notion of order is dictated by access to resolved atom positions, providing rigidity and flexibility information with low and high experimental B-factors, while disorder is associated with the missing (non-resolved) residues. Nonetheless, some rigid regions can be found in disorder regions. Using ensembles of IDPs, their local conformations were analyzed in the light of a structural alphabet. An entropy index derived from this structural alphabet allowed us to propose a continuum of states from rigidity to flexibility and finally disorder. In this study, the analysis was extended to comparing these results to disorder predictions, underlying a limited correlation, and so opening new ideas to characterize and predict disorder. MDPI 2020-07-20 /pmc/articles/PMC7408373/ /pubmed/32698546 http://dx.doi.org/10.3390/biom10071080 Text en © 2020 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
de Brevern, Alexandre G.
Analysis of Protein Disorder Predictions in the Light of a Protein Structural Alphabet
title Analysis of Protein Disorder Predictions in the Light of a Protein Structural Alphabet
title_full Analysis of Protein Disorder Predictions in the Light of a Protein Structural Alphabet
title_fullStr Analysis of Protein Disorder Predictions in the Light of a Protein Structural Alphabet
title_full_unstemmed Analysis of Protein Disorder Predictions in the Light of a Protein Structural Alphabet
title_short Analysis of Protein Disorder Predictions in the Light of a Protein Structural Alphabet
title_sort analysis of protein disorder predictions in the light of a protein structural alphabet
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408373/
https://www.ncbi.nlm.nih.gov/pubmed/32698546
http://dx.doi.org/10.3390/biom10071080
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