Insights into the Structure of Large-Ring Cyclodextrins through Molecular Dynamics Simulations in Solution

Area of Science:

• Supramolecular Chemistry
• Computational Chemistry
• Biophysical Chemistry

Background:

• Cyclodextrins (CDs) are cyclic oligosaccharides with a hydrophobic cavity and hydrophilic exterior.
• Large-ring cyclodextrins (LRCDs) with high degrees of polymerization (DP) are less characterized in solution compared to their crystalline states.
• Understanding the solution conformation of LRCDs is crucial for their applications.

Purpose of the Study:

• To investigate the structural deformations and energetics of large-ring cyclodextrins (DP 26-100) in aqueous solution using molecular dynamics (MD) simulations.
• To compare the solution structures of LRCDs with their known crystalline conformations.
• To explore the conformational flexibility and potential cavity formation in LRCDs.

Main Methods:

• Molecular dynamics (MD) simulations were performed for cyclodextrins with DP 26, 30, 55, 70, 85, and 100.
• The AMBER parm99 force field and TIP3P explicit water model were employed.
• Simulations were conducted for 10.0 ns to observe structural evolution.

Main Results:

• The solution structures of cyclodextrin 26 (CD26) differed significantly from its crystalline conformation, with characteristic 'flips' disappearing early in the simulation.
• Larger cyclodextrins (DP > 26) demonstrated substantial flexibility, adopting various folding modes.
• Observed conformations included circular and elongated loops, double helical strands, spiral regions, dendritic folds, and bending, indicating complex three-dimensional structures.

Conclusions:

• Large-ring cyclodextrins exhibit dynamic and flexible structures in solution, deviating from rigid crystalline forms.
• The diverse folding patterns suggest the presence of multiple, adaptable cavity-like regions within LRCDs.
• These findings support the hypothesis that large-ring cyclodextrins can possess more than one functional cavity.