3-O-Sulfation induces sequence-specific compact topologies in heparan sulfate that encode a dynamic sulfation code

Holmes, Samuel G.; Nagarajan, Balaji; Desai, Umesh R.

doi:10.1016/j.csbj.2022.07.013

Cited by 9 publications

(14 citation statements)

References 83 publications

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“…Similar to the work of Holmes et al . 92 performed for heparan sulfate oligosaccharides, we could see that the first GlcN6S-IdoA2S glycosidic linkage minimum (φ ∼ −80° and ψ ∼ −50°) corresponds to the increased curvature of HP, and it is much more pronounced for the explicit solvent where more curved structures are observed. This minimum is barely visible in the heatmaps of the glycosidic linkages in the implicit solvent.…”

Section: Resultsmentioning

confidence: 91%

“…We suppose that the presence of the ions may favorize the curvature of HP due to Na + interactions with sulfate groups. It was previously reported that ions could stabilize/favor curved structure of other GAGs. , …”

Section: Resultsmentioning

confidence: 99%

“…It was previously reported that ions could stabilize/favor curved structure of other GAGs. 92,93 To look for the potential changes at a shorter timescale of the MD simulation and to check for the consistency of the calculations, five repeats of the 200 ns MD runs for each of the tested water models were performed. Although overall results were similar (Figures S5 and S6 and Table S1), some differences were observed for the analyzed descriptors in the shorter MD runs.…”

Section: Journal Of Chemicalmentioning

confidence: 99%

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Solvent Model Benchmark for Molecular Dynamics of Glycosaminoglycans

Marcisz

Samsonov

2023

J. Chem. Inf. Model.

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In computational studies of glycosaminoglycans (GAGs), a group of anionic, periodic linear polysaccharides, so far there has been very little discussion about the role of solvent models in the molecular dynamics simulations of these molecules. Predominantly, the TIP3P water model is commonly used as one of the most popular explicit water models in general. However, there are numerous alternative explicit and implicit water models that are neglected in the computational research of GAGs. Since solvent-mediated interactions are particularly important for GAG dynamic and structural properties, it would be of great interest for the GAG community to establish the solvent model that is suited the best in terms of the quality of theoretically obtained GAG parameters and, at the same time, would be reasonably demanding in terms of computational resources required. In this study, heparin (HP) was simulated using five implicit and six explicit solvent models with the aim to find out how different solvent models influence HP's molecular descriptors in the molecular dynamics simulations. Here, we initiate the search for the most appropriate solvent representation for GAG systems and we hope to encourage other groups to contribute to this highly relevant subject.

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Section: Resultsmentioning

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Journal Of Chemicalmentioning

confidence: 99%

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Solvent Model Benchmark for Molecular Dynamics of Glycosaminoglycans

Marcisz

Samsonov

2023

J. Chem. Inf. Model.

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“…HS exhibits a linear helical form with unique small “kink(s)” possible where D -glucuronic acid is epimerized to L -iduronic acid due to the greater flexibility in glycosidic linkages around IdoA residues, which provides focal regions in the HS chain that can adopt a more compact conformation containing 3- O sulfation motifs [ 84 ]. 3- O sulfation in HS chains is generally rare, however, an abundance of HS3ST isoforms is present in tissues with varying substrate specificity making this functional structural modification of HS enigmatic.…”

Section: The Cell Instructive Properties Of Gagsmentioning

confidence: 99%

“…3- O sulfation in HS chains is generally rare, however, an abundance of HS3ST isoforms is present in tissues with varying substrate specificity making this functional structural modification of HS enigmatic. HS is a repository of the most diverse “sulfation codes” of any GAG [ 84 ]. This provides HS with the ability to selectively recognize and interact with specific proteins [ 85 , 86 , 87 ].…”

Section: The Cell Instructive Properties Of Gagsmentioning

confidence: 99%

HS, an Ancient Molecular Recognition and Information Storage Glycosaminoglycan, Equips HS-Proteoglycans with Diverse Matrix and Cell-Interactive Properties Operative in Tissue Development and Tissue Function in Health and Disease

Hayes

Melrose

2023

IJMS

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Heparan sulfate is a ubiquitous, variably sulfated interactive glycosaminoglycan that consists of repeating disaccharides of glucuronic acid and glucosamine that are subject to a number of modifications (acetylation, de-acetylation, epimerization, sulfation). Variable heparan sulfate chain lengths and sequences within the heparan sulfate chains provide structural diversity generating interactive oligosaccharide binding motifs with a diverse range of extracellular ligands and cellular receptors providing instructional cues over cellular behaviour and tissue homeostasis through the regulation of essential physiological processes in development, health, and disease. heparan sulfate and heparan sulfate-PGs are integral components of the specialized glycocalyx surrounding cells. Heparan sulfate is the most heterogeneous glycosaminoglycan, in terms of its sequence and biosynthetic modifications making it a difficult molecule to fully characterize, multiple ligands also make an elucidation of heparan sulfate functional properties complicated. Spatio-temporal presentation of heparan sulfate sulfate groups is an important functional determinant in tissue development and in cellular control of wound healing and extracellular remodelling in pathological tissues. The regulatory properties of heparan sulfate are mediated via interactions with chemokines, chemokine receptors, growth factors and morphogens in cell proliferation, differentiation, development, tissue remodelling, wound healing, immune regulation, inflammation, and tumour development. A greater understanding of these HS interactive processes will improve therapeutic procedures and prognoses. Advances in glycosaminoglycan synthesis and sequencing, computational analytical carbohydrate algorithms and advanced software for the evaluation of molecular docking of heparan sulfate with its molecular partners are now available. These advanced analytic techniques and artificial intelligence offer predictive capability in the elucidation of heparan sulfate conformational effects on heparan sulfate-ligand interactions significantly aiding heparan sulfate therapeutics development.

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Biological Codes: A Field Guide for Code Hunters

Prinz¹

2023

Biol Theory

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3-O-Sulfation induces sequence-specific compact topologies in heparan sulfate that encode a dynamic sulfation code

Cited by 9 publications

References 83 publications

Solvent Model Benchmark for Molecular Dynamics of Glycosaminoglycans

Solvent Model Benchmark for Molecular Dynamics of Glycosaminoglycans

HS, an Ancient Molecular Recognition and Information Storage Glycosaminoglycan, Equips HS-Proteoglycans with Diverse Matrix and Cell-Interactive Properties Operative in Tissue Development and Tissue Function in Health and Disease

Biological Codes: A Field Guide for Code Hunters

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