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

Annemarie Danielsson; Małgorzata 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

Comput Biol Chem. 2022 Aug:99:107716. doi: 10.1016/j.compbiolchem.2022.107716. Epub 2022 Jun 23.

Authors

Annemarie Danielsson¹, Małgorzata M Kogut², Martyna Maszota-Zieleniak¹, Pradeep Chopra³, Geert-Jan Boons⁴, Sergey A Samsonov⁵

Affiliations

¹ Faculty of Chemistry, University of Gdańsk, ul. Wita Stwosza 63, 80-308 Gdańsk, Poland.
² Faculty of Chemistry, University of Gdańsk, ul. Wita Stwosza 63, 80-308 Gdańsk, Poland; Intercollegiate Faculty of Biotechnology of University of Gdańsk and Medical University of Gdańsk, ul. Abrahama 58, 80-307 Gdańsk, Poland.
³ Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA.
⁴ Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA; Department of Chemistry, University of Georgia, Athens, GA 30602, USA; Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Center for Biomolecular Research, Utrecht University, 3584 CG Utrecht, the Netherlands.
⁵ Faculty of Chemistry, University of Gdańsk, ul. Wita Stwosza 63, 80-308 Gdańsk, Poland. Electronic address: sergey.samsonov@ug.edu.pl.

PMID: 35810558
DOI: 10.1016/j.compbiolchem.2022.107716

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; Molecular dynamics; Principal component analysis; Sugar binding specificity.

MeSH terms

Glycosaminoglycans / chemistry
Glycosaminoglycans / metabolism
Heparitin Sulfate / metabolism
Molecular Dynamics Simulation*
Protein Binding
Sulfates* / chemistry
Sulfates* / metabolism

Substances

Glycosaminoglycans
Sulfates
Heparitin Sulfate