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Molecular Dynamics-Based Comparative Analysis of Chondroitin and Dermatan Sulfates

Glycosaminoglycans (GAGs) are a class of linear anionic periodic polysaccharides containing disaccharide repetitive units. These molecules interact with a variety of proteins in the extracellular matrix and so participate in biochemically crucial processes such as cell signalling affecting tissue re...

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Autores principales: Pągielska, Marta, Samsonov, Sergey A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953526/
https://www.ncbi.nlm.nih.gov/pubmed/36830616
http://dx.doi.org/10.3390/biom13020247
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author Pągielska, Marta
Samsonov, Sergey A.
author_facet Pągielska, Marta
Samsonov, Sergey A.
author_sort Pągielska, Marta
collection PubMed
description Glycosaminoglycans (GAGs) are a class of linear anionic periodic polysaccharides containing disaccharide repetitive units. These molecules interact with a variety of proteins in the extracellular matrix and so participate in biochemically crucial processes such as cell signalling affecting tissue regeneration as well as the onset of cancer, Alzheimer’s or Parkinson’s diseases. Due to their flexibility, periodicity and chemical heterogeneity, often termed “sulfation code”, GAGs are challenging molecules both for experiments and computation. One of the key questions in the GAG research is the specificity of their intermolecular interactions. In this study, we make a step forward to deciphering the “sulfation code” of chondroitin sulfates-4,6 (CS4, CS6, where the numbers correspond to the position of sulfation in NAcGal residue) and dermatan sulfate (DS), which is different from CSs by the presence of IdoA acid instead of GlcA. We rigorously investigate two sets of these GAGs in dimeric, tetrameric and hexameric forms with molecular dynamics-based descriptors. Our data clearly suggest that CS4, CS6 and DS are substantially different in terms of their structural, conformational and dynamic properties, which contributes to the understanding of how these molecules can be different when they bind proteins, which could have practical implications for the GAG-based drug design strategies in the regenerative medicine.
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spelling pubmed-99535262023-02-25 Molecular Dynamics-Based Comparative Analysis of Chondroitin and Dermatan Sulfates Pągielska, Marta Samsonov, Sergey A. Biomolecules Article Glycosaminoglycans (GAGs) are a class of linear anionic periodic polysaccharides containing disaccharide repetitive units. These molecules interact with a variety of proteins in the extracellular matrix and so participate in biochemically crucial processes such as cell signalling affecting tissue regeneration as well as the onset of cancer, Alzheimer’s or Parkinson’s diseases. Due to their flexibility, periodicity and chemical heterogeneity, often termed “sulfation code”, GAGs are challenging molecules both for experiments and computation. One of the key questions in the GAG research is the specificity of their intermolecular interactions. In this study, we make a step forward to deciphering the “sulfation code” of chondroitin sulfates-4,6 (CS4, CS6, where the numbers correspond to the position of sulfation in NAcGal residue) and dermatan sulfate (DS), which is different from CSs by the presence of IdoA acid instead of GlcA. We rigorously investigate two sets of these GAGs in dimeric, tetrameric and hexameric forms with molecular dynamics-based descriptors. Our data clearly suggest that CS4, CS6 and DS are substantially different in terms of their structural, conformational and dynamic properties, which contributes to the understanding of how these molecules can be different when they bind proteins, which could have practical implications for the GAG-based drug design strategies in the regenerative medicine. MDPI 2023-01-28 /pmc/articles/PMC9953526/ /pubmed/36830616 http://dx.doi.org/10.3390/biom13020247 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pągielska, Marta
Samsonov, Sergey A.
Molecular Dynamics-Based Comparative Analysis of Chondroitin and Dermatan Sulfates
title Molecular Dynamics-Based Comparative Analysis of Chondroitin and Dermatan Sulfates
title_full Molecular Dynamics-Based Comparative Analysis of Chondroitin and Dermatan Sulfates
title_fullStr Molecular Dynamics-Based Comparative Analysis of Chondroitin and Dermatan Sulfates
title_full_unstemmed Molecular Dynamics-Based Comparative Analysis of Chondroitin and Dermatan Sulfates
title_short Molecular Dynamics-Based Comparative Analysis of Chondroitin and Dermatan Sulfates
title_sort molecular dynamics-based comparative analysis of chondroitin and dermatan sulfates
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953526/
https://www.ncbi.nlm.nih.gov/pubmed/36830616
http://dx.doi.org/10.3390/biom13020247
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