Molecular dynamics-based descriptors of 3-O-Sulfated Heparan sulfate as contributors of protein binding specificity

Annemarie Danielsson; Malgorzata M. Kogut; Martyna Maszota-Zieleniak; Pradeep Chopra; Geert-Jan Boons; Sergey A. Samsonov

doi:10.1016/j.compbiolchem.2022.107716

Molecular dynamics-based descriptors of 3-O-Sulfated Heparan sulfate as contributors of protein binding specificity

Annemarie Danielsson, Malgorzata M. Kogut, Martyna Maszota-Zieleniak, Pradeep Chopra, Geert-Jan Boons, Sergey A. Samsonov

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Glycosaminoglycans are linear periodic and anionic polysaccharides found in the extracellular matrix, involved in a range of key biochemical processes as a result of their interactions with a variety of protein partners. Due to the template-less synthesis, high flexibility and charge of GAGs, as well as the multipose binding of GAG ligands to receptors, the specificity of GAG-protein interactions can be difficult to elucidate. In this study we propose a set of MD-based descriptors of unbound Heparan Sulfate hexasaccharides that can be used to characterize GAGs and explain their binding affinity to a set of protein receptors. With the help of experimental data on GAG-protein binding affinity, we were able to further characterize the nature of this interaction in addition to providing a basis for predictor functions of GAG-protein binding specificity.

Original language	English
Article number	107716
Pages (from-to)	1-14
Number of pages	14
Journal	Computational Biology and Chemistry
Volume	99
DOIs	https://doi.org/10.1016/j.compbiolchem.2022.107716
Publication status	Published - Aug 2022

Bibliographical note

Funding Information:
This study was funded by the National Science Centre of Poland (Narodowe Centrum Nauki, grant number UMO-2018/31/G/ST4/00246 ) and the National Institute of Health (grant HLBI R01HL151617 for G.-J. B.) We thank dr. Margrethe Gaardløs for technical support.

Publisher Copyright:
© 2022 Elsevier Ltd

Keywords

Glycosaminoglycans
Sugar binding specificity
Molecular dynamics
Principal component analysis

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10.1016/j.compbiolchem.2022.107716

1-s2.0-S1476927122000962-mainFinal published version, 5.55 MBLicence: Taverne

Cite this

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title = "Molecular dynamics-based descriptors of 3-O-Sulfated Heparan sulfate as contributors of protein binding specificity",

abstract = "Glycosaminoglycans are linear periodic and anionic polysaccharides found in the extracellular matrix, involved in a range of key biochemical processes as a result of their interactions with a variety of protein partners. Due to the template-less synthesis, high flexibility and charge of GAGs, as well as the multipose binding of GAG ligands to receptors, the specificity of GAG-protein interactions can be difficult to elucidate. In this study we propose a set of MD-based descriptors of unbound Heparan Sulfate hexasaccharides that can be used to characterize GAGs and explain their binding affinity to a set of protein receptors. With the help of experimental data on GAG-protein binding affinity, we were able to further characterize the nature of this interaction in addition to providing a basis for predictor functions of GAG-protein binding specificity.",

keywords = "Glycosaminoglycans, Sugar binding specificity, Molecular dynamics, Principal component analysis",

author = "Annemarie Danielsson and Kogut, \{Malgorzata M.\} and Martyna Maszota-Zieleniak and Pradeep Chopra and Geert-Jan Boons and Samsonov, \{Sergey A.\}",

note = "Funding Information: This study was funded by the National Science Centre of Poland (Narodowe Centrum Nauki, grant number UMO-2018/31/G/ST4/00246 ) and the National Institute of Health (grant HLBI R01HL151617 for G.-J. B.) We thank dr. Margrethe Gaardl{\o}s for technical support. Publisher Copyright: {\textcopyright} 2022 Elsevier Ltd",

year = "2022",

month = aug,

doi = "10.1016/j.compbiolchem.2022.107716",

language = "English",

volume = "99",

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journal = "Computational Biology and Chemistry",

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AU - Danielsson, Annemarie

AU - Kogut, Malgorzata M.

AU - Maszota-Zieleniak, Martyna

AU - Chopra, Pradeep

AU - Boons, Geert-Jan

AU - Samsonov, Sergey A.

N1 - Funding Information: This study was funded by the National Science Centre of Poland (Narodowe Centrum Nauki, grant number UMO-2018/31/G/ST4/00246 ) and the National Institute of Health (grant HLBI R01HL151617 for G.-J. B.) We thank dr. Margrethe Gaardløs for technical support. Publisher Copyright: © 2022 Elsevier Ltd

PY - 2022/8

Y1 - 2022/8

N2 - Glycosaminoglycans are linear periodic and anionic polysaccharides found in the extracellular matrix, involved in a range of key biochemical processes as a result of their interactions with a variety of protein partners. Due to the template-less synthesis, high flexibility and charge of GAGs, as well as the multipose binding of GAG ligands to receptors, the specificity of GAG-protein interactions can be difficult to elucidate. In this study we propose a set of MD-based descriptors of unbound Heparan Sulfate hexasaccharides that can be used to characterize GAGs and explain their binding affinity to a set of protein receptors. With the help of experimental data on GAG-protein binding affinity, we were able to further characterize the nature of this interaction in addition to providing a basis for predictor functions of GAG-protein binding specificity.

AB - Glycosaminoglycans are linear periodic and anionic polysaccharides found in the extracellular matrix, involved in a range of key biochemical processes as a result of their interactions with a variety of protein partners. Due to the template-less synthesis, high flexibility and charge of GAGs, as well as the multipose binding of GAG ligands to receptors, the specificity of GAG-protein interactions can be difficult to elucidate. In this study we propose a set of MD-based descriptors of unbound Heparan Sulfate hexasaccharides that can be used to characterize GAGs and explain their binding affinity to a set of protein receptors. With the help of experimental data on GAG-protein binding affinity, we were able to further characterize the nature of this interaction in addition to providing a basis for predictor functions of GAG-protein binding specificity.

KW - Glycosaminoglycans

KW - Sugar binding specificity

KW - Molecular dynamics

KW - Principal component analysis

UR - https://www.scopus.com/pages/publications/85133912868

U2 - 10.1016/j.compbiolchem.2022.107716

DO - 10.1016/j.compbiolchem.2022.107716

M3 - Article

SN - 1476-9271

VL - 99

SP - 1

EP - 14

JO - Computational Biology and Chemistry

JF - Computational Biology and Chemistry

M1 - 107716

ER -

Molecular dynamics-based descriptors of 3-O-Sulfated Heparan sulfate as contributors of protein binding specificity

Abstract

Bibliographical note

Keywords

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