Conformation of amylose in aqueous solution: Small-angle X-ray scattering measurements and simulations

Small-angle X-ray scattering profiles for an amylose fragment (maltoheptaos e) in aqueous solution were observed and compared with the theoretical prof iles calculated for an ensemble of chain conformations generated by molecul ar dynamics simulations and Monte Carlo simulations. The Monte Carlo result s based on the disaccharide conformation energy map obtained without explic itly considering surrounding water molecules were in satisfactory agreement with the experimental results, provided that the effective dielectric cons tant was set to four. In contrast, the results of the fully solvated molecu lar dynamics simulations performed using the Cff91, Cff, Gromos, Glycam93, and Glycam99 force-fields were unexpectedly different from each other. Amon g them, Cff91 gave most satisfactory agreement with experiment, but the oth er fields yielded conformations that were somewhat or highly extended. It w as also shown that recently developed Glycam99 is a significant improvement over Glycam 93. The representative snapshots of the two successful simulat ions resembled the regular helical structure reported by Goldsmith ct al. ( J. Mol. Biol. 1982, 156, 411). The source of the large force-field dependen ce was investigated by examining the various Ramachandran-like plots for th e glycosidic torsion angles. For comparison, similar plots of ab initio ene rgy for maltose (i.e., a fragment with two glucose units) were also calcula ted 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 proce dure to remedy this over-preference can be devised, although a need of furt her elaboration of the force-field is indicated. The significance of force- fields is also illustrated in modeling a cyclodextrin composed of 14 glucos e units.