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Open AccessArticle

Constructing 3-Dimensional Atomic-Resolution Models of Nonsulfated Glycosaminoglycans with Arbitrary Lengths Using Conformations from Molecular Dynamics

1
Department of Pharmaceutical Sciences and Administration, University of New England School of Pharmacy, 716 Stevens Avenue, Portland, ME 04103, USA
2
Graduate School of Biomedical Science and Engineering, University of Maine, 5775 Stodder Hall, Orono, ME 04469, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(20), 7699; https://doi.org/10.3390/ijms21207699
Received: 10 September 2020 / Revised: 15 October 2020 / Accepted: 15 October 2020 / Published: 18 October 2020
Glycosaminoglycans (GAGs) are the linear carbohydrate components of proteoglycans (PGs) and are key mediators in the bioactivity of PGs in animal tissue. GAGs are heterogeneous, conformationally complex, and polydisperse, containing up to 200 monosaccharide units. These complexities make studying GAG conformation a challenge for existing experimental and computational methods. We previously described an algorithm we developed that applies conformational parameters (i.e., all bond lengths, bond angles, and dihedral angles) from molecular dynamics (MD) simulations of nonsulfated chondroitin GAG 20-mers to construct 3-D atomic-resolution models of nonsulfated chondroitin GAGs of arbitrary length. In the current study, we applied our algorithm to other GAGs, including hyaluronan and nonsulfated forms of dermatan, keratan, and heparan and expanded our database of MD-generated GAG conformations. Here, we show that individual glycosidic linkages and monosaccharide rings in 10- and 20-mers of hyaluronan and nonsulfated dermatan, keratan, and heparan behave randomly and independently in MD simulation and, therefore, using a database of MD-generated 20-mer conformations, that our algorithm can construct conformational ensembles of 10- and 20-mers of various GAG types that accurately represent the backbone flexibility seen in MD simulations. Furthermore, our algorithm efficiently constructs conformational ensembles of GAG 200-mers that we would reasonably expect from MD simulations. View Full-Text
Keywords: molecular dynamics; glycosaminoglycan; proteoglycan; hyaluronan; dermatan; keratan; heparan; carbohydrate conformation; carbohydrate flexibility; glycosidic linkage; ring pucker; force field; explicit solvent molecular dynamics; glycosaminoglycan; proteoglycan; hyaluronan; dermatan; keratan; heparan; carbohydrate conformation; carbohydrate flexibility; glycosidic linkage; ring pucker; force field; explicit solvent
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Whitmore, E.K.; Martin, D.; Guvench, O. Constructing 3-Dimensional Atomic-Resolution Models of Nonsulfated Glycosaminoglycans with Arbitrary Lengths Using Conformations from Molecular Dynamics. Int. J. Mol. Sci. 2020, 21, 7699.

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