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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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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7408373 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT debrevernalexandreg analysisofproteindisorderpredictionsinthelightofaproteinstructuralalphabet |