TY - JOUR
T1 - Molecular dynamics-based descriptors of 3-O-Sulfated Heparan sulfate as contributors of protein binding specificity
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 - http://www.scopus.com/inward/record.url?scp=85133912868&partnerID=8YFLogxK
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 -