title: Binding mode and free energy prediction of fisetin/β-cyclodextrin inclusion complexes.
abstract: In the present study, our aim is to investigate the preferential binding mode and encapsulation of the flavonoid fisetin in the nano-pore of β-cyclodextrin (β-CD) at the molecular level using various theoretical approaches: molecular docking, molecular dynamics (MD) simulations and binding free energy calculations. The molecular docking suggested four possible fisetin orientations in the cavity through its chromone or phenyl ring with two different geometries of fisetin due to the rotatable bond between the two rings. From the multiple MD results, the phenyl ring of fisetin favours its inclusion into the β-CD cavity, whilst less binding or even unbinding preference was observed in the complexes where the larger chromone ring is located in the cavity. All MM- and QM-PBSA/GBSA free energy predictions supported the more stable fisetin/β-CD complex of the bound phenyl ring. Van der Waals interaction is the key force in forming the complexes. In addition, the quantum mechanics calculations with M06-2X/6-31G(d,p) clearly showed that both solvation effect and BSSE correction cannot be neglected for the energy determination of the chosen system.
authors.affiliation: Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Bodee
authors.initials: B
authors.lastname: Nutho
authors.affiliation: Nanoscience and Technology Program, Graduate School, Chulalongkorn University, Bangkok, 10330, Thailand.
authors.forename: Wasinee
authors.initials: W
authors.lastname: Khuntawee
authors.affiliation: National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), 111 Thailand Science Park, Thanon Phahonyothin Tambon Khlong Nueng, Amphoe Khlong Luang, Pathum Thani 12120, Thailand.
authors.forename: Chompoonut
authors.initials: C
authors.lastname: Rungnim
authors.affiliation: Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Piamsook
authors.initials: P
authors.lastname: Pongsawasdi
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Vienna 1090, Austria ; Institute of Theoretical Chemistry, University of Vienna, Vienna 1090, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Wolschann
authors.affiliation: Institute of Theoretical Chemistry, University of Vienna, Vienna 1090, Austria.
authors.forename: Alfred
authors.initials: A
authors.lastname: Karpfen
authors.affiliation: Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand.
authors.forename: Nawee
authors.initials: N
authors.lastname: Kungwan
authors.affiliation: Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Thanyada
authors.initials: T
authors.lastname: Rungrotmongkol
keywords: MM-PBSA; QM-PBSA; cyclodextrin; fisetin; flavonoid; molecular dynamics simulation