Molecular dynamics (MD) simulations were used to investigate the binding of β-blocker drugs propranolol and atenolol to the chiral molecular micelle (MM), poly-(sodium undecyl-(L)-leucine-valine) poly(SULV)). The MM contained twenty covalently bonded surfactants each with a chiral dipeptide headgroup. Poly(SULV) is used in capillary electrophoresis to separate enantiomers of chiral drugs. One enantiomer of each β-blocker was docked into one of four MM binding pockets and MD simulations were carried out. Propranolol binding free energy calculations showed that (S)-propranolol associated more strongly with poly(SULV) than (R)-propranolol. Analogous calculations showed that the association of atenolol enantiomers with the MMM were very similar. Solvent accessible surface area analyses showed that in the preferred propranolol binding pockets the ligand’s rings penetrated deeply into the poly(SULV) core. Atenolol however, bound primarily near the surface. (S)-propranol was found to associate more strongly with poly(SULV) than (R)-propranolol because it experienced stronger hydrogen bonding interactions with the MM.

Investigation of β-blocker assocation with a chiral molecular micelle by means of molecular dynamics simulations

249th National Meeting (2015)

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