Conformation of Amylose in Aqueous Solution:  Small-Angle X-ray Scattering Measurements and Simulations

Small-angle X-ray scattering profiles for an amylose fragment (maltoheptaose) in aqueous solution were observed and compared with the theoretical profiles calculated for an ensemble of chain conformations generated by molecular dynamics simulations and Monte Carlo simulations. The Monte Carlo results based on the disaccharide conformation energy map obtained without explicitly considering surrounding water molecules were in satisfactory agreement with the experimental results, provided that the effective dielectric constant was set to four. In contrast, the results of the fully solvated molecular dynamics simulations performed using the Cff91, Cff, Gromos, Glycam93, and Glycam99 force-fields were unexpectedly different from each other. Among them, Cff91 gave most satisfactory agreement with experiment, but the other fields yielded conformations that were somewhat or highly extended. It was also shown that recently developed Glycam99 is a significant improvement over Glycam 93. The representative snapshots of the two successful simulations resembled the regular helical structure reported by Goldsmith et al. (J. Mol. Biol. 1982, 156, 411). The source of the large force-field dependence was investigated by examining the various Ramachandran-like plots for the glycosidic torsion angles. For comparison, similar plots of ab initio energy for maltose (i.e., a fragment with two glucose units) were also calculated at the Hartree−Fock level, although in a simplified manner. These plots suggest that the extended conformation arises from too strong a preference for a certain rotational isomeric state of the glycosidic linkage. A procedure to remedy this over-preference can be devised, although a need of further elaboration of the force-field is indicated. The significance of force-fields is also illustrated in modeling a cyclodextrin composed of 14 glucose units.