Conformational analysis and molecular dynamics simulation of alpha-(1-->2) and alpha-(1-->3) linked rhamnose oligosaccharides: reconciliation with optical rotation and NMR experiments

Biopolymers. 1997 Jan;41(1):83-96. doi: 10.1002/(SICI)1097-0282(199701)41:1<83::AID-BIP8>3.0.CO;2-Z.

Abstract

Molecular mechanics and dynamics calculations were carried out on the disaccharides alpha-L-Rhap-(1-->2)-alpha-L-Rhap-(1-->OMe) (1) and alpha-L-Rhap-(1-->3)-alpha-L-Rhap-(1-->OMe) (2), and the trisaccharide alpha-L-Rhap-(1-->2)-alpha-L-Rhap-(1--> 3)-alpha-L-Rhap-(1-->OMe) (3). The semiflexible conformational behavior of these molecules was characterized by the occupation of a combination of different glycosidic linkage and side-chain conformational positions whose relative occupations were sensitive to dielectric screening. Molecular dynamics simulations of the trisaccharide 3 showed little difference between the linkage conformations in the trisaccharide and the component disaccharides 1 and 2 Experimental optical rotation data of 1 and 2 were obtained as a function of temperature in varying solvents. The molecular models were combined with the semiempirical theory of Stevens and Sathyanarayana to yield calculated optical rotations. Interpretation of the data of both 1 and 2 implied that a combination of conformations, both in glycosidic and side-chain positions, could explain the experimental data. Solvents effects were important in influencing the conformational mix and averaged optical rotation. Three-bond heteronuclear coupling constants 3JC H were obtained for the glycosidic linkages of 1 and 2 in D2O and DMSO. Analysis of the coupling constants with a Karplus curve showed that small reductions in the glycosidic torsion angles of the conformations of the models used here of ca. 10 degrees-15 degrees in phi and 5 degrees-10 degrees in psi were required to give better agreement with experiment; a combination of conformations for both 1 and 2 was consistent with the data. There was a negligible influence on the coupling constants of 1 on changing the solvent from D2O to DMSO.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbohydrate Conformation
  • Carbohydrate Sequence
  • Computer Simulation
  • Magnetic Resonance Spectroscopy / methods
  • Molecular Sequence Data
  • Oligosaccharides / chemistry*
  • Optical Rotation
  • Rhamnose / chemistry*
  • Thermodynamics

Substances

  • Oligosaccharides
  • Rhamnose