Assessment of sulfobutylether-beta-cyclodextrin as a promising Fluorometholone molecule container: DFT, Docking, Molecular dynamics and MM-PBSA free energy calculations

In the present work, the preferential binding mode of Fluorometholone (FLU) drug into the nanopores of two cyclodexterins, b-cyclodextrin (b-CD) and sulfobutylether-b-cyclodextrin (SEB-b-CD), are theoretically investigated using density functional theory (DFT), Docking, the molecular dynamics (MD) simulation and MM-PBSA free energy calculations. The computational results reveal that hydrogen bonds (HBs) and van der Waals (vdW) interactions have the significant roles in the stability of FLU into the cavity of b-CD and SBE-b-CD structures in the aqueous phase. It is found that the complexing ability of FLU is significantly increased from -62.245 kJ/mol in native b-CD to -89.677 kJ/mol in SEB-b-CD by introducing sulfobutylether groups to the hydroxyl groups of the macromolecule. In addition, a remarkable enhancement of the solubility of SBE-β-CD, compared to the native β-cyclodextrin, is observed. The inclusion process of FLU drug into SEB-β-CD improves the polarity of FLU@SBE-β-CD complex and enhances its solubility. Furthermore, the conformational stability of the top-scored FLU@β-CD and FLU@SEB-β-CD docked models is analysed by molecular dynamics simulation. The MM-PBSA freeenergy approach approves more binding affinity of FLU drug into the SEB-β-CD cavity. The obtained data aim to explore the potential application of SEB-β-CD macromolecule for designing and developing pharmacological formulations.