title: Glycosaminoglycan monosaccharide blocks analysis by quantum mechanics, molecular dynamics, and nuclear magnetic resonance.
abstract: Glycosaminoglycans (GAGs) play an important role in many biological processes in the extracellular matrix. In a theoretical approach, structures of monosaccharide building blocks of natural GAGs and their sulfated derivatives were optimized by a B3LYP6311ppdd//B3LYP/6-31+G(d) method. The dependence of the observed conformational properties on the applied methodology is described. NMR chemical shifts and proton-proton spin-spin coupling constants were calculated using the GIAO approach and analyzed in terms of the method's accuracy and sensitivity towards the influence of sulfation, O1-methylation, conformations of sugar ring, and ω dihedral angle. The net sulfation of the monosaccharides was found to be correlated with the (1)H chemical shifts in the methyl group of the N-acetylated saccharides both theoretically and experimentally. The ω dihedral angle conformation populations of free monosaccharides and monosaccharide blocks within polymeric GAG molecules were calculated by a molecular dynamics approach using the GLYCAM06 force field and compared with the available NMR and quantum mechanical data. Qualitative trends for the impact of sulfation and ring conformation on the chemical shifts and proton-proton spin-spin coupling constants were obtained and discussed in terms of the potential and limitations of the computational methodology used to be complementary to NMR experiments and to assist in experimental data assignment.
authors.affiliation: Structural Bioinformatics, BIOTEC, TU Dresden, Tatzberg 47-51, 01307 Dresden, Germany.
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Samsonov
authors.affiliation: Institute of Medical Physics and Biophysics, University of Leipzig, Härtelstr. 16-18, 04107 Leipzig, Germany.
authors.forename: Stephan
authors.identifier: 0000-0002-8843-3358
authors.initials: S
authors.lastname: Theisgen
authors.affiliation: Institute of Medical Physics and Biophysics, University of Leipzig, Härtelstr. 16-18, 04107 Leipzig, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Riemer
authors.affiliation: Institute of Medical Physics and Biophysics, University of Leipzig, Härtelstr. 16-18, 04107 Leipzig, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Huster
authors.affiliation: Structural Bioinformatics, BIOTEC, TU Dresden, Tatzberg 47-51, 01307 Dresden, Germany.
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Pisabarro
mesh_terms: D006025:Glycosaminoglycans / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D009005:Monosaccharides / Q000737:chemistry*; D011522:Protons; D011789:Quantum Theory
chemical_list: D006025:Glycosaminoglycans; D009005:Monosaccharides; D011522:Protons