An improved force field for conformational analysis of sulfated polysaccharides

Abstract

A force field to be used in molecular mechanics studies of sulfated polysaccharides with explicit account of water and counterion interactions was derived from the analysis of six crystal structures of sulfated monosaccharide salts. The force field is based on Allinger's MM2, and was developed starting from the parameters used in previous studies of heparin and related oligosaccharides. While the novel parameters have been derived empirically, use of the atomic charge distribution obtained from ab initio quantum-mechanical computations, at the 6–31 + G** level, improves the quality of structural fitting significantly. The overall discrepancy between the positions of the nonhydrogen atoms determined by X-ray diffractometry and those corresponding to the minimum-energy structure is 0.21 Å. While most geometrical features of both carbohydrate and sulfate moieties are reproduced satisfactorily, in some cases (particularly in the case of the Na+ salt of α-methyl-4-O-sulfogalactopyranoside) the hydrogen bond pattern is altered by energy minimization, probably due to errors in the balance of the strong electrostatic forces. © 1997 by John Wiley & Sons, Inc.