Abstract

Most drug molecules are chiral meaning they are found in two different mirror image forms.  The subtle differences in the structures of these two forms or enantiomers often dramatically affects the drug’s interaction with biological receptors.  For example, one enantiomer may produce the desired therapeutic effect, while the other may be inactive or even toxic.  In this project, molecular dynamics computer simulations were used to investigate the binding of the chiral drug atenolol to a chiral molecular micelle.  The enantiomers of chiral drugs are often separated based upon their interactions with the molecular micelle used in this study.  Therefore, the goal of this research was to characterize the interactions at the molecular level in order to gain insight into the molecular basis for these separations.   The atenolol molecule was docked into six different binding pockets on the molecular micelle and then molecular dynamics simulations were run to monitor how the drug and micelle atoms moved over time.  The molecular dynamics trajectories were then analyzed to assess chiral hydrogen bonding between the drug and micelle and the motion of the drug molecule in each pocket. These and other analyses allowed the best molecular micelle binding pocket to be identified.