A combined nuclear magnetic resonance and molecular dynamics study of the two structural motifs for mixed-linkage β-glucans: methyl β-cellobioside and methyl β-laminarabioside

The conformational and hydration properties of the two disaccharides methyl beta-cellobioside and methyl beta-laminarabioside were investigated by NMR spectroscopy and explicit solvation molecular dynamics simulations using the carbohydrate solution force field (CSFF). Adiabatic maps produced with this force field displayed 4 minima A: (Phi = 300 degrees, Psi = 280 degrees), B: (Phi = 280 degrees, Psi = 210 degrees), C: (Phi = 260 degrees, Psi = 60 degrees), and D: (Phi = 60 degrees, Psi = 260 degrees) for methyl beta-cellobioside and 3 minima A: (Phi = 290 degrees, Psi = 130 degrees), B: (Phi = 270 degrees, Psi = 290 degrees), and C: (Phi = 60 degrees, Psi = 120 degrees) for methyl beta-laminarabioside. Molecular dynamics simulations were initiated from all minima. For each disaccharide, the simulation started from the A minimum was conducted for 50 ns, while the other minima were explored for 10 ns. The simulations revealed two stable minima for both compounds. For methyl beta-cellobioside, the simulation minima in aqueous solution were shifted from their adiabatic map counterparts, while the simulation minima for methyl beta-laminarabioside coincided with the corresponding adiabatic map minima. To validate the simulation results, NMR-derived NOEs and coupling constants across the glycoside linkage, (3)J(HC) and (3)J(CH), were compared with values calculated from the MD trajectories. For each disaccharide, the best agreement was obtained for the simulations started at the A minimum. For both compounds, inter-ring water bridges in combination with the direct hydrogen bonds between the same groups were found to be determining factors for the overall solution structure of the disaccharides which differed from solid-state structures. Comparison with helical parameters showed that the preferred glycosidic dihedral configurations in the methyl beta-cellobioside simulation were not highly compatible with the structure of cellulose, but that curdlan helix structures agreed relatively well with the methyl beta-laminarabioside simulation. Polymers generated using glycosidic dihedral angles from the simulations revealed secondary structure motifs that that may help to elucidate polymer associations and small-molecule binding. (C) 2009 Elsevier Ltd. All rights reserved.