Large-ring cyclodextrins. A molecular dynamics study of the conformational dynamics and energetics of CD10, CD14 and CD26

Abstract

Molecular dynamics simulations in water were performed on the three largest large-ring cyclodextrins (LR-CD) for which X-ray data is available -CD10, CD14 and CD26. The Glycam-04 force field in AMBER and explicit water molecules (TIP3P) were used in the 20.0 ns simulations. Small variations about the starting conformation of CD10 were detected. Different structural motifs were monitored for CD14 that may represent chiral species of particular interest for exploring supramolecular and chiral molecular recognition effects: broadly opened macroring, that resembles the initial geometry of CD10 but in larger scale, a big circular loop with a small helical turn, deformed figure eight conformation, and a symmetrically squeezed open form ("a dumbbell"). The final geometry of CD14 is free of additional strain introduced by band-flips. The preferred conformation of CD26 contains a small helix and an extended helical portion that transforms also to an arc and a loop. Two modifications of the equilibration step of the simulation protocol were tested.

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

“…4 and S6, ESI. † The differences between the results obtained with the two Glycam parameterizations (Glycam04 44,46 and Glycam06 (this work)) manifest themselves from the very first stages of the conformational search for CD26 (Fig. S1, ESI, † e.g., the geometry after the first 500.0 ps).…”

“…S12, ESI †). The different orientation of the loops is the striking dissimilarity between the representative confor-mations of CD26, obtained with Glycam-04 44,46 and Glycam-06. This observation originates from the differences in the estimates for the relative energies of the flip conformations by the a The ratio of the eigenvalues of the first three most significant eigenvectors with the explained variance in percent (weight).…”

“…This is in accord with our conclusions made earlier for CD14. 44,48,50 Two loops situated in mutually perpendicular planes were clearly seen in the average structure of CD14 when the Glycam04 parameterization was used. 45 The eigenvector explaining the largest part for the variance of the trajectory of CD14 corresponded to a deformation, for which a conformation containing big and small loops, situated in perpendicular planes, assumes an intermediate symmetrical figureeight-looking geometry.…”

“…38 The conformations of some LR-CDs were systematically examined using molecular dynamics simulations as a conformational search protocol. [39][40][41][42][43][44][45][46][47][48][49][50][51] We started our studies by performing 5.0 ns simulations on several LR-CDs with degrees of polymerization in the range from 40 to 100. 39 The results were indicative for a variety of geometries with more than one small cavity.…”

Dynamic Chiral Cyclohexanohemicucurbit[12]uril

“…2,3 Several macrocycles differing considerably in conformation from their smaller counterparts have been reported. Cyclodextrins (CDs) containing more than 9 glycose units, termed large-ring CDs (LR-CDs) 4 , can assume a helical folding arrangement, e.g., the 26-membered CD [5][6][7][8][9] . LR-CDs with 14 units have been shown to adopt a conformation that resembles a concave polygon.…”