Molecular dynamics simulations on inclusion complexes for chiral enantiomers with heterocyclic cyclodecapeptide

Cyclic peptides are exciting novel hosts for chiral and molecular recognition. In this work, the four inclusion complexes of heterocyclic cyclodecapeptide (HCD) with the 1-phenyl-1-propanol (MPP, M = R or S) enantiomer and 1-phenylpropan-2-amine (NPA, N = R or S) enantiomer are firstly investigated using molecular dynamics (MD) simulations. The corresponding association free energy was derived by integrating the potential of mean force (PMF) along an ordering reaction coordinate. The obtained results indicated that SPP exhibits the highest propensity to associate with HCD. Ranking for binding to HCD are respectively SPP > RPP and SPA > RPA. The differences in binding energy indicated that the HCD could differentiate the MPP and NPA enantiomers. The global minimum found on the free energy curve was further examined by running additional MD simulations. Analysis of the trajectories suggests that all four inclusion complexes appear to be thermodynamically stable. The present work sheds new light on HCD as a desirable host molecule for chiral and molecular recognition.