Molecular dynamics-based descriptors of 3-O-Sulfated Heparan sulfate as contributors of protein binding specificity. (August 2022)

• Record Type: Journal Article
• Authors: Danielsson, Annemarie; Kogut, Małgorzata M.; Maszota-Zieleniak, Martyna; Chopra, Pradeep; Boons, Geert-Jan; Samsonov, Sergey A.
• Is Part Of: Computational biology and chemistry. Volume 99(2022)
• Publication Date: 2022-08
• Subjects: Glycosaminoglycans -- Sugar binding specificity -- Molecular dynamics -- Principal component analysis; GAG Glycosaminoglycan -- HP Heparin -- HS Heparan Sulfate -- DS Dermatan Sulfate -- CS Chondroitin Sulfate -- KS Keratan Sulfate -- HA Hyaluronic Acid -- ATIII Antithrombin III -- PCA Principal Component Analysis -- PC Principal Component -- MD Molecular Dynamics -- RMSD Root Mean Square Deviation -- H-bond Hydrogen Bond -- HC Hierarchical Clustering -- RFU Relative Fluorescent Unit; Chemistry -- Data processing -- Periodicals; Biology -- Data processing -- Periodicals; Biochemistry -- Data processing; Biology -- Data processing; Molecular biology -- Data processing; Periodicals; Electronic journals; 542.85
• DOI: 10.1016/j.compbiolchem.2022.107716
• Languages: English
• ISSNs: 1476-9271

Abstract

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. Graphical Abstract: ga1 Highlights: Deeper insight into the specificity of heparan sulfate-protein binding. Physicochemical descriptors of heparan sulfate linked to binding affinity. Molecular dynamics of heparan sulfate used for binding specificity determination. Principal component analysis of physico-chemical descriptors of heparan sulfate.