Explicit-Solvent Molecular Dynamics Simulations of the β(1→3)- and β(1→6)-Linked Disaccharides β-Laminarabiose and β-Gentiobiose in Water

Abstract

The conformational preferences about the glycosidic linkages present in β-laminarabiose and β-gentiobiose in water are investigated by comparing molecular dynamics (MD) simulations with results from NMR spectroscopy (coupling constants, NOE-derived distances), X-ray crystallography (structures), and molecular mechanics (adiabatic energy maps). The simulations are performed using the OPLS−AA−SEI force field recently developed for hexopyranoses and extended to account for the properties of the linkages present in the two disaccharides. The experimental and theoretical results for β-laminarabiose are very consistent and reveal a clear correlation between the conformation around the dihedral angle ψ and the presence of an interresidue hydrogen bond (from the 4-hydroxyl group of the reducing residue to the ring oxygen of the nonreducing residue). The solvent (water) plays an essential role in determining the preferential orientation about ψ, by dramatically reducing the strength of this intramolecular hydrogen bond. Application of the OPLS−AA−SEI force field to β-gentiobiose requires significant adjustments of the torsional parameters and electrostatic scaling scheme. After optimization of the force field based on ab initio calculations in a vacuum and on the experimental population profile around the dihedral angle ω in water, the OPLS−AA−SEI force field is able to give a realistic representation of the conformational behavior of the β(1→6) linkage on the nanosecond time scale. As expected, the glycosidic dihedral angles in this linkage present an enhanced flexibility compared to the β(1→3) linkage. The results of the two simulations point (in line with previous studies) toward the need of developing a new Karplus-type equation relating hetero-nuclear 3JC,H coupling constants to the glycosidic dihedral angle φ. They also suggest that the Karplus-type equation of Stenutz et al. for the homo-nuclear 3JH,H coupling constant is superior to the widely used equation of Haasnoot et al.