NMR-Analysis, Karplus Equations, and Solution Geometry of Beta-1,6-Glycosidic Linkages

Session: 
PS2 Poster session 2 Even numbers
Code: 
P64
Location (hall): 
Foyer
Start/end time: 
Tuesday, July 2, 2019 - 15:45 to 17:15
Andreas
Franz

Andreas Franz1, Amelia Watson1

1University of the Pacific, Stockton, United States

Variations of the Karplus equation[1,2] have been used widely to describe the dependency of NMR scalar coupling constants on the dihedral angle between the coupled nuclei. Specifically, carbohydrates have seen successful applications of the Karplus equations to problems of conformational analysis.[3] Due to the number of possible constitutional and configurational isomers, oligosaccharides have the greatest potential diversity and complexity among biomacromolecules. Oligosaccharides are present in all life kingdoms[4] and are essential to the biochemistry of protein folding/quality control,[5] immune response to infection, cell-cell interaction,[6] fertilization,[7] cancerogenesis,[8] cancer metastasis,[9] blood group antigens, and neuronal development.[10-13] Conformational flexibility increases the information content stored in such structures even further and influences the glycans’ biochemistry. The objective of the study here was to develop new Karplus equations for β-1,6-linked oligosaccharides. Conformational analysis of the glycosidic linkage was achieved by NMR spectroscopy and MD simulations. Karplus equations for the HCCH- fragment and the HCCC-fragment (ωangle) were developed from coupling constant calculations (Gaussian ’09, PCM water model) fitted to J = Acos2(θ)+Bcos(θ)+C and J = Acos2(θ+D)+Bcos(θ+E)+C. MD-histograms of dihedral angles were extracted (GLYCAM06, TIP3P water model) and were weighted by the Karplus equation to yield J-values. Preliminary test datashowed good fit between computed and experimental coupling constants in various β-1,6-linked oligosaccharides. 

Figure 1. NMR-tools and computational methods for the development of Karplus equations.

References: 
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