Molecular motions of alpha-cyclodextrin on a dodecyl chain studied by molecular dynamics simulations

Motions of an alpha-cyclodextrin (alpha-CD) molecule on a dodecyl chain adopting the all-trans conformation were investigated in the presence of water by molecular dynamics simulations with CVFF force fields, where the trimethylammonium group of dodecyltrimethylammonium bromide (DTAB) is protruded outside the secondary hydroxyl rim of alpha-CD (the secondary-in structure). The alpha-CD molecule shuttled rapidly on the chain without decomplexation. This rapid motion is consistent with the NMR data. The plane formed by 6 O4 atoms of alpha-CD is most populated between the C6 and C7 atoms of DTAB. This structure is very close to that estimated by NMR. The alpha-CD molecule underwent a restricted rotation in a range of 60 degrees with regard to the plane of the dodecyl chain: this plane at the most population is middle between the two diagonal lines of the normal hexagon formed by 6 O4 atoms of alpha-CD. The published NMR data were reanalyzed in terms of the rotation angle, and a slightly better structure was obtained. The distortion of the alpha-CD cavity from the normal hexagon was decreased upon complex formation with DTAB. The deviation of the center of alpha-CD from the center of the dodecyl chain predicted by molecular dynamics simulations is consistent with the NMR data. The secondary-in structure is energetically more stable than the primary-in structure, as calculated by molecular mechanics with CVFF and Amber force fields. This result is consistent with the NMR data. Molecular dynamics simulations were also carried out for the primary-in structure. Some of the results are close to those of the secondary-in structure.