Use of Circular Statistics To Model αMan-(1→2)-αMan and αMan-(1→3)-α/βMan O-Glycosidic Linkage Conformation in ¹³C-Labeled Disaccharides and High-Mannose Oligosaccharides

Abstract

A new experimental method, MA'AT analysis, has been applied to investigate the conformational properties of Oglycosidic linkages in several biologically important mannosecontaining di-and oligosaccharides. Methyl α-D-mannopyranosyl-(1→2)-α-D-mannopyranoside (2), methyl α-D-mannopyranosyl-(1→3)-α-D-mannopyranoside (3), and methyl α-D-mannopyranosyl-(1→3)-β-D-mannopyranoside (4) were prepared with selective 13 C-enrichment to enable the measurement of NMR scalar couplings across their internal O-glycosidic linkages. Density functional theory (DFT) was used to parameterize equations for J CH and J CC values in 2−4 that are sensitive to phi (ϕ) and psi (ψ). The experimental J-couplings and parameterized equations were treated using a circular statistics algorithm encoded in the MA'AT program. Conformations about ϕ and ψ treated using single-state von Mises models gave excellent fits to the ensembles of redundant J-couplings. Mean values and circular standard deviations (CSDs) for each linkage torsion angle ϕ (CSD) and ψ (CSD) in 2, −29°(25°) and 20°(22°); in 3, −36°(36°) and 8°(27°); in 4, −37°(34°) and 10°(26°); ϕ = H1′−C1′−O1′− CX and ψ = C1′−O1′−CX−HX (CX = aglycone carbon) were compared to histograms obtained from 1 μs aqueous molecular dynamics (MD) simulations and X-ray database statistical analysis. MA'AT-derived models of ψ were in very good agreement with the MD and X-ray data, but not those of ϕ, suggesting a need for force field revision. The effect of structural context on linkage conformation was also investigated in four selectively 13 C-labeled homomannose tri-and tetrasaccharides using the MA'AT method. In the cases examined, context effects were found to be small.

A detailed picture of a protein–carbohydrate hydrogen-bonding network revealed by NMR and MD simulations

“…2019 ) or ϕ H = −40°, ψ H = 33° ( Säwén et al . 2010 ) or ϕ H = −29°, ψ H = 20° ( Zhang et al . 2019 ).…”

Conformational analysis of the disaccharide methyl α-D-mannopyranosyl-(1→3)-2-O-acetyl-β-D-mannopyranoside monohydrate

“…Recent NMR studies (Zhang et al, 2019) using MA 0 AT analysis indicate that methyl -d-mannopyranosyl-(1!3)-d-mannopyranoside, (IV), which is devoid of the O-acetyl group at C2 of (II), adopts a linkage conformation in aqueous solution similar to that found in crystalline (II). For (IV), mean values of the H1 0 -C1 0 -O1 0 -C3 (') and C1 0 -O1 0 -C3-H3 ( ) torsion angles of À37 and 10 , respectively, were found in solution, while the crystal structure of (II) gives corresponding values of À43 and À6 (Table 2).…”

Three-Dimensional Structures of Carbohydrates and Where to Find Them

“…Support of experimental data with computer simulations can significantly improve quality of 3D structures. Quantum mechanics [ 100 , 102 , 103 , 104 , 105 , 106 ] and molecular dynamics modeling [ 107 , 108 , 109 , 110 , 111 ] are commonly applied to conformation search and NMR signal prediction.…”