Stereoselective inclusion mechanism of ketoprofen into β-cyclodextrin: insights from molecular dynamics simulations and free energy calculations

摘要: The host–guest inclusion mechanism formed between β-cyclodextrin and those poorly water-soluble drug molecules has important applications in supramolecular chemistry, biology pharmacy. In this work, the chiral recognition ability of to one nonsteroidal anti-inflammatory drugs, ketoprofen, been systematically investigated using molecular dynamics free energy simulation methods. R- S-enantiomers ketoprofen were explicitly bound within cyclodextrin cavity our simulations, respectively. consistent with experimental observations, tiny structural difference two isomers could be observed. Calculated absolute binding energies adapted biasing force (ABF) method MM/GBSA approach for both are comparable values. Significant fluctuations along MD trajectory have profiles calculated different approaches reveal that prefers carboxylate group facing wider edge β-cyclodextrin. Similar enantiomers obtained ABF calculations indicate it is very hard separate identify conjugates framework natural