Comparative Interaction Studies of Quercetin with 2-Hydroxyl-propyl-β-cyclodextrin and 2,6-Methylated-β-cyclodextrin

Quercetin is a well-known natural product that can exert beneficial properties on human health. However, due to its low solubility its bioavailability is limited. In the present study, Here, we examine whether its formulation with two cyclodextrins (CDs) may enhance its pharmacological profile. Comparative interaction studies of quercetin with 2-hydroxyl-propyl-β-cyclodextrin (2HP-β-CD) and 2,6-methylated cyclodextrin (2,6Me-β-CD) were performed using NMR spec-troscopy and Molecular Dynamics (MD) simulations. Using T1 relaxation experiments and 2D DOSY it was illustrated that both cyclodextrin vehicles can host quercetin. Calculations of abso-lute binding free energies show that quercetin binds favorably to both 2,6Me-β-CD and 2HP-β-CD. MM/GBSA results show equally favorable binding of quercetin in the two CDs. Fluo-rescence spectroscopy shows moderate binding of quercetin in 2HP-β-CD (520 M-1) and 2,6Me-β-CD (770 M-1). Thus, we propose that both formulations (2HP-β-CD:quercetin, 2,6Me-β-CD:quercetin) could be further explored and exploited as small molecule carriers in bio-logical and clinical studies. In this entry we provide all input files for absolute free energy calculations using the non-equilibrium scheme of GROMACS 2021.4. Please cite this as "Vakali et al, Comparative Interaction Studies of Quercetin with 2-Hydroxyl-propyl-β-cyclodextrin and 2,6-Methylated-β-cyclodextrin, Molecules, 2022" The file "input_files_non_equilibrium_AFE_hpbcd7.tar.gz" holds input files required to run the non-equilibrium free energy workflow for 2-Hydroxyl-propyl-β-cyclodextrin/Quercetin complex using GROMACS.2021.4 The following files and directories/folders have been generated: README.txt input_files_non_equilibrium_AFE_hpbcd7/ stateA_water/ Contains the 96 .gro and .tpr files required to run QUE solvation leg starting from λ=0 stateB_water/ Contains the 96 .gro and .tpr files required to run QUE solvation leg starting from λ=1 stateA_protein/ Contains the 96 .gro and .tpr files required to run QUE coupling leg starting from λ=0 stateB_protein/ Contains the 96 .gro and .tpr files required to run QUE coupling leg starting from λ=1 topology_scripts/ Contains the topology files for complex and solvent phase, mdp files containing all the input parameters to run each transition, grompp* python script files to produce the 95 tpr files to perform each transition for each system and the restraints.py script provided from http://www.alchemistry.org/wiki/Absolute_Binding_Free_Energy_-_Gromacs_2016 to compute analytically the restraints applied for these calculation