Computational study on the conformations of CD38 and inclusion complexes of some lower-size large-ring cyclodextrins

• Limited number of modes determine the overall deformations of the macroring of CD38.
• A three-turn helix conformation shaped as a short tube was found for CD38.
• Computationally were examined for the first time inclusion complexes of LR-CDs.

The conformations of CD38 were examined by conformational search with molecular dynamics simulations using the Glycam04 force field. The results were compared with previous ones for CD26, the largest cyclodextrin for which crystal data are available. Principal component analysis (PCA) was applied for post-processing of the simulation trajectories. Limited number of modes determine the overall deformations of the macroring of CD38. The longer perimeter of the macroring allowed the formation of a form not observed so far – a three-turn helix shaped as a short tube. In analogy with CD26, significant participation was monitored for conformations of CD38 with one-turn spirals at the opposite sides of the macroring linked together from the ‘bottom’ and from the ‘top’ with extended bridge spacers. Computationally were examined for the first time inclusion complexes of some lower-size LR-CDs, namely complexes of CDn (n = 13, 14, 26) with adamantane and of CD14 with 1-hydroxyadamantane. The macroring conformation of CD13 was not altered by the inclusion of the substrate molecule which acquired preferred positioning not in the middle of the cavity but rather close to the glucose residues at one of the sides. The same positioning of the small molecule in the cavity of the more flexible CD14 macroring enhanced the appearance of bent onto two conformation of this cyclodextrin. The most interesting behaviour presented the complex of CD26 with adamantane in which case the small molecule acts as a ‘nucleation center’ for the formation of a second helical turn about the substrate molecule.