Insights into the Structure of Large-Ring Cyclodextrins through Molecular Dynamics Simulations in Solution

Molecular dynamics simulations were carried out using the AMBER parm99 force field and explicit water molecules (TIP3P) to gain insight into the structural deformations and energetics of several large-ring cyclodextrins (with a degree of polymerization 26, 30, 55, 70, 85, and 100) in solution. The structures displayed by CD26 during the MD simulation (10.0 ns) did not correspond to the conformation in the crystalline state. The two “flips” present in the macroring of CD26 in the crystal state disappeared after 1.5 and 3.0 ns simulations, respectively. The larger CDs bear a considerable degree of flexibility. They display different modes of folding and cavity-like regions of different sizes and shapes:  circular and elongated loops of variable size, orientated in different fashion; portions of a double helical strand with the two single helices parallel to each other (CD30, CD70); a helix of three turns and a serpentiform portion containing six loops (CD55); a cone-shaped spiral region (CD70); a rounded dendritic fold with several arbitrarily oriented small loops on the surface of the clustering (CD85); three spiral portions and a tendency for bending into two (CD100). These results support the hypothesis for the existence of more than one cavity in large-ring cyclodextrins.