Structural Dynamics of Some Large-Ring Cyclodextrins. A Molecular Dynamics Study: An Analysis of Force Field Performance

Molecular dynamics simulations were performed on four large ring cyclodextrins (LR-CDs), CD14, CD21, CD26 and CD28, both in gas phase and in water solution. Four different force fields (parm94, parm99, glycam2000a and MM3*) were used to examine their dependence with the results. The differences were not significant when parm99 and glycam2000a were used. Parm94 and MM3* results differ considerably due to inadequate bending parameters (parm94) or due to a strong stabilization by the intramolecular hydrogen bonds between hydroxyl groups. Simulations in the gas phase show that the CDs are elongated and twisted, and that cavities typical for the native CDs (CDn, n = 6, 7, 8) are not present. Simulations in water solution produced average structures that do not correspond to the conformations in the crystalline state. The LR-CDs are highly flexible and this could favor the formation of inclusion complexes through the intermediation of some other molecules that could fit to the smaller and more specific cavities they have.On sabbatical leave from the Institute of Organic Chemistry with Center of Phytochemistry, Bulgarian Academy of Science, ul. Acad. G. Bonchev, bloc 9, 1113 Sofia, Bulgaria