These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Inclusion mechanism of steroid drugs into beta-cyclodextrins. Insights from free energy calculations.
    Author: Cai W, Sun T, Liu P, Chipot C, Shao X.
    Journal: J Phys Chem B; 2009 Jun 04; 113(22):7836-43. PubMed ID: 19425557.
    Abstract:
    The inclusion of hydrocortisone, progesterone, and testosterone into the cavity of beta-cyclodextrin (beta-CD) following two possible orientations was investigated using molecular dynamics simulations and free-energy calculations. The free-energy profiles that delineate the inclusion process were determined using an adaptive biasing force. The present results reveal that although the free-energy surfaces feature two local minima corresponding to a partial and a complete inclusion, the former mode is markedly preferred, irrespective of the orientation. Ranking the propensity of the three steroidal molecules to associate with beta-CD, viz. progesterone>testosterone>hydrocortisone, is shown to be in excellent agreement with experiment. This conclusion is further supported by independent calculations relying on alchemical transformations in conjunction with free energy perturbation, wherein the relative binding free energy for the three steroids was estimated. In addition, decomposition of the potentials of mean force into free-energy contributions and significant decrease in the total hydrophobic surface area suggest that by and large, van der Waals and hydrophobic interactions constitute the main driving forces responsible for the formation of the inclusion complexes. Analysis of their structural features from the molecular dynamics trajectories brings to light different hydrogen-bonding patterns that are characterized by distinct dynamics and stabilities.
    [Abstract] [Full Text] [Related] [New Search]