Inclusion Mechanism of Steroid Drugs into β-Cyclodextrins. Insights from Free Energy Calculations

摘要: The inclusion of hydrocortisone, progesterone, and testosterone into the cavity β-cyclodextrin (β-CD) following two possible orientations was investigated using molecular dynamics simulations free-energy calculations. profiles that delineate process were determined an adaptive biasing force. present results reveal although surfaces feature local minima corresponding to a partial complete inclusion, former mode is markedly preferred, irrespective orientation. Ranking propensity three steroidal molecules associate with β-CD, viz. progesterone > shown be in excellent agreement experiment. This conclusion further supported by independent calculations relying on alchemical transformations conjunction free energy perturbation, wherein relative binding for steroids estimated. In addition, decomposition potentials mean f...