Conformations of some large-ring cyclodextrins derived from conformational search with molecular dynamics simulations and principal component analysis.

Principal component analysis (PCA) was applied for postprocessing of trajectories from conformational search, based on 50.0 ns molecular dynamics (MD) simulations, with the purpose to elucidate the conformations of some large-ring cyclodextrins (LR-CDs), CDn (n = 24, 25, 26, 27, 28, 29). The dominant PCA modes for concerted motions of the macroring atoms were monitored in a lower-dimension subspace. The first 10 lowest indexed modes describe more than 90% of the total atomic motions in all cases, with about 85% (CD27, CD29) to more than 90% (CD24, CD25) contribution coming from the six highest-eigenvalue principal components. Representative average geometries of the cyclodextrin macrorings were also obtained for the whole simulation and for the five 10.0 ns time intervals of the simulation. Two conformations for CD26, the largest LR-CD for which X-ray data is available, are characterized by possessing, respectively, one and two helical turns. Resemblance to computed representative conformations of CD26 in water was found for CD27 and CD28, with the similarity being better expressed for the former case. Only CD24, among the two smaller size LR-CDs, displays resemblance during short simulation intervals to one of the conformations of CD26. The formation of small loops of six to seven glucose units is a favorable deformation mode of the macrorings. Besides, once a small loop of six to seven glucoses is formed, the next natural mode for deformation of the macromolecule is toward the creation of a short helix that further enhances the stability of the structure. The average geometry of CD29 has no likeness at all to the conformations of CD26. Thus, the difference of three glucose units between CD26 and CD29 already influences significantly the shape of the most probable conformation.