Large‐ring cyclodextrins. Further support for the preferred conformations of CD26 in water solution: Molecular dynamics studies on CD26‐derived conformations of CDn (n = 24, 25, 27, 28, 29, 30)

Abstract

AbstractMolecular dynamics (MD) simulations in water solution were performed on six large ring cyclodextrins (LR‐CDs) with a degree of polymerization (DP) 24, 25, 27, 28, 29, and 30, using as starting structures geometries derived from CD26, which was studied previously by MD. The present research was aimed at further extending our knowledge on the structural dynamics and the energetics of this new class of compounds, focusing on several representatives flanking CD26, the largest LR‐CD for which X‐ray data are available. The most recent parameterization for carbohydrates, Glycam‐04, and explicit water molecules (TIP3P) were used in the 10.0‐ns simulations. Preceding 10.0‐ns simulations of CD26, with the AMBER parm99 force field, revealed that the overall shape of the macromolecule did not change significantly during the last 5.0‐ns simulations. We now further test for the probability of prevalence of this conformation by using a different force field and by examining the effect of the size of the macro‐ring on the preferred conformations of LR‐CDs with DP within a range of 24–30. Indeed, we found CD26‐like geometries present for CD25, CD27, and CD28, which could be interpreted as an indication for an enhanced stability of the CD26 conformation in water solution. Again, we witnessed high flexibility of the macro‐cycles, and different local structural motifs were detected: twisted helical double parallel strand (CD25, CD30), single helix of three turns (CD29), a spiral (CD25, CD27, CD30), open‐shaped loops and helical turns (CD28; “CD26‐like geometry”), a rectangular cavity (CD24), a triple‐lobe fragment (CD29) or a portion shaped like a jaw (CD24, CD27), and an overall shape of the macromolecule that resembled a butterfly (CD27) or “X” (CD28). Thus, we conclude that the same conformation of CD26 could be also the preferred conformation in water solution of other LR‐CDs with DP in the close vicinity of 26. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007