Conformational differences between alpha-cyclodextrin in aqueous solution and in crystalline form. A molecular dynamics study.

The computer simulation technique of molecular dynamics is a powerful tool to delineate the conformational differences between a molecule in different environments. As an illustration, the difference between an alpha-cyclodextrin molecule in aqueous solution and in crystalline form is determined. Two molecular dynamics simulations are compared. In one simulation, one alpha-cyclodextrin form in a "truncated octahedron box" containing 611 water molecules is simulated over 90 picoseconds to mimic the solution structure. In the other simulation, the crystalline form is modelled by a molecular dynamics simulation of four unit cells in space group P2(1)2(1)2(1) containing 16 alpha-cyclodextrin molecules and 96 water molecules over a period of 15 picoseconds. The solution structure of alpha-cyclodextrin deviates by about 0.1 nm from that in the crystal and shows twice as much mobility of the atoms. The experimentally observed twist of glucose unit 5 out of alignment with the other five glucose units in the alpha-cyclodextrin torus that is present in the crystal simulation, disappears in the simulation in solution, but the glucosidic torsion angles around the ring remain asymmetric. The hydrogen-bonding patterns in crystal and in solution are rather different. This means that in a crystal structure, the molecule and its (hydration) hydrogen-bonding scheme represent only one static minimum energy picture, whereas the molecular dynamics simulations yield a description of all the many hydrogen-bonding configurations that can occur in solution.