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

Journal: Computational biology and chemistry 2022;99():107716

PMID: 35810558

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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.

Address: Faculty of Chemistry, University of Gdańsk, ul. Wita Stwosza 63, 80-308 Gdańsk, Poland.; 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.; Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA.; 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.; Faculty of Chemistry, University of Gdańsk, ul. Wita Stwosza 63, 80-308 Gdańsk, Poland. Electronic address: [email protected].

DOI: 10.1016/j.compbiolchem.2022.107716

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MeSH Terms: Glycosaminoglycans, Heparitin Sulfate, Molecular Dynamics Simulation, Protein Binding, Sulfates