Computational study on the intramolecular self-organization of the macrorings of some ‘giant’ cyclodextrins (CDn, n = 40, 70, 85, 100)

Abstract

The conformations of some 'giant' cyclodextrins (CDn, n = 40, 70, 85, 100) were examined by molecular dynamic simulations using the Glycam06 force field. CD14 and CD26, the largest cyclodextrins, for which crystallographic data are available, were also studied as reference structures. Principal component analysis was used for the analyses of the simulation trajectories. In cases where band-flips were not present in the starting geometry (e.g. CD40), flips appeared later during the conformational search. The results for CDn (n = 14, 26, 40) confirmed an interesting observation for the distribution of band-flips along the perimeters of the macrorings, namely, band-flips separate portions of lengths of about six or twelve glucoses. This allows the formation of energetically favorable small loops of six-seven glucoses or the creation of short two-turns single helices that further enhance the stability of the structures. It was found that flip dihedrals define distributions of fragment lengths 12-6, 12-12, and 12-12-6 residues in the larger CDs (CD70, CD85, CD100). Contributions from 77% (CD40) to 88% (CD26) are from the first three highest-eigenvalue principal components, i.e., a limited number of modes determine the overall deformations of the macrorings. The flexibility of the macrorings increases, going from CD40 to the CDs, with higher degrees of polymerization. CD14 and CD26 present interesting cases - CD26 manifests domination of one deformation mode (ca. 72%), whereas CD14 demonstrates significantly higher flexibility. These results confirm our earlier conclusion, namely, LR-CDs may have more than one cavity. Thus they have the potential to accommodate more than one substrate molecule, as well as larger species by an 'induced fit' mechanism.

Comparison of Implicit and Explicit Solvation Models forIota-Cyclodextrin Conformation Analysis from Replica Exchange Molecular Dynamics

“…The boat form of C 5 5 identified from visual inspection from the side hints that it is likely to be encumbered by steric hindrance for guest molecule inclusion. Although the twisted and boat forms were observed in the previous study using classical MD simulation, our analysis provides information in quantifiable terms.…”

“…By using classical MD simulation of CD14 in solution at room temperature the deformed conformations from the crystal structure, such as the open form, twisted shape containing two loops, and the dumbbell shape, were found. 16,17 Moreover, the geometry of CD26 was studied by density functional theory (DFT) in the gas phase and was found to be in agreement with its crystal structure, which is solvated in water. 18 Although classical MD is a useful method to study the conformation of LR-CDs, it requires long-time dynamics in order to overcome the energy barrier among local minima.…”

“…The larger size rings of LR-CDs have a more flexible structure, where multiple cavities in the LR-CDs could be frequently observed. By using classical MD simulation of CD14 in solution at room temperature the deformed conformations from the crystal structure, such as the open form, twisted shape containing two loops, and the dumbbell shape, were found. , Moreover, the geometry of CD26 was studied by density functional theory (DFT) in the gas phase and was found to be in agreement with its crystal structure, which is solvated in water …”

Formation and molecular dynamics simulation of inclusion complex of large‐ring cyclodextrin and 4‐terpineol

“…It can be seen from Figure 4 (CD14‐ter) that the formation of CD14 may have two false cavities (Ivanov, 2012). When viewed from the Z ‐axis direction, the guest molecule occupied a certain position in the two cavities, but it can be clearly observed in the complex formed by CD26 that the guest molecule only occupied the cavity on one side (Ivanov et al., 2015). In a stable state, the center of the cavity was occupied by the guest molecule.…”