Enhanced stability of a naringenin/2,6-dimethyl β-cyclodextrin inclusion complex: Molecular dynamics and free energy calculations based on MM- and QM-PBSA/GBSA

The structure, dynamic behavior and binding affinity of the inclusion complexes between naringenin and the two cyclodextrins (CDs), beta-CD and its 2,6-dimethyl derivative (DM-beta-CD), were theoretically studied by multiple molecular dynamics simulations and free energy calculations. Naringenin most likely prefers to bind with CDs through the phenyl ring. Although a lower hydrogen bond formation of naringenin with the 3-hydroxyl group of DM-beta-CD (relative to beta-CD) was observed, the higher cavity could encapsulate almost the whole naringenin molecule. In contrast for the naringenin/beta-CD complex, the phenyl ring feasibly passed through the primary rim resulting in the chromone ring binding inside instead. MM-PBSA/GBSA and QM-PBSA/GBSA binding free energies strongly suggested a greater stability of the naringenin/DM-beta-CD inclusion complex. Van der Waals force played an important role as the key guest-host interaction for the complexation between naringenin and each cyclodextrin. (C) 2014 Elsevier Inc. All rights reserved.