A comparison of distance geometry and molecular dynamics simulation techniques for conformational analysis of β‐cyclodextrin

Distance geometry and molecular dynamics simulation techniques were compared in their ability to search the conformational potential energy surface of β‐cyclodextrin. Structures generated by the DISGEO program were minimized using three different atomic point charge sets. Some of these structures were used as starting points for molecular dynamics simulation in vacuo at 298K. The distance geometry results showed that the global features of the conformational potential energy surface were generally independent of the point charge set. The distance geometry technique was able to find structures of lower energy than those obtained by direct minimization of the X‐ray or neutron diffraction structures. However, the molecular dynamics simulation technique was consistently able to find structures of lower energy than those generated by distance geometry. Root mean square fit of the trajectory structures to the starting structure showed that the simulation allowed the molecule to explore regions of the potential energy surface in the neighborhood of the starting structure. Both the distance geometry and molecular dynamics simulation techniques showed that β‐cyclodextrin can adopt a wide range of conformations in the gas phase and that these conformations are much less symmetrical than the crystalline structure.