title: 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.
abstract: The structure, dynamic behavior and binding affinity of the inclusion complexes between naringenin and the two cyclodextrins (CDs), β-CD and its 2,6-dimethyl derivative (DM-β-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-β-CD (relative to β-CD) was observed, the higher cavity could encapsulate almost the whole naringenin molecule. In contrast for the naringenin/β-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-β-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.
authors.affiliation: Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Waratchada
authors.initials: W
authors.lastname: Sangpheak
authors.affiliation: Nanoscience and Technology Program, Graduate School, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Wasinee
authors.initials: W
authors.lastname: Khuntawee
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: Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Piamsook
authors.initials: P
authors.lastname: Pongsawasdi
authors.affiliation: Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand. Electronic address: t.rungrotmongkol@gmail.com.
authors.forename: Thanyada
authors.initials: T
authors.lastname: Rungrotmongkol
mesh_terms: D000272:Adipates / Q000737:chemistry*; D004355:Drug Stability; D044950:Flavanones / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D013386:Succinates / Q000737:chemistry*; D013816:Thermodynamics; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000272:Adipates; D044950:Flavanones; D013386:Succinates; D047392:beta-Cyclodextrins; C437084:poly(tetramethylene succinate-co-tetramethylene adipate); C038119:heptakis(2,6-O-dimethyl)beta-cyclodextrin; C005273:naringenin
keywords: Binding free energy; Cyclodextrin; Inclusion complex; MM- and QM-PBSA/GBSA; Naringenin