A computational approach on the stereoselective binding of peptides from aqueous medium with endo-functionalized molecular tubes

The need to obtain enantiomerically pure isomers of amino acids and peptides is often realized in the field of biology and in the pharmaceutical industry. Research is underway to devise simple methods for the chiral resolution of amino acids from their racemic mixtures. Inspired by this objective, in our present work, we have computationally shown the possibility of chiral separation of the enantiomeric pairs of two model peptides, namely, (D,L)-aspargine and (D,L)-phenylalanine, in the presence of water. For this purpose, we have used two synthetic supramolecular receptors named host-1a and host-1b, respectively. Molecular dynamics simulations and quantum chemical methods are employed to analyze the structural features and the energy aspects involved in the separation process. The information obtained at the molecular level helps us gain better insights into the key interactions that operate to produce such enantioselectivity. We have also investigated the dynamics and changes in the water structure in the vicinity of the host molecules, both in the presence and absence of the model peptides. The D- and L-isomers of the same peptide undergo complexation with a particular host molecule registering a difference of more than 1.5 kcal mol−1 (obtained from PMF and MM-PBSA analyses) in their respective energies. This indicates that the chiral separation of the peptides with the help of these endo-fuctionalized molecular tube receptors may be energetically feasible. The connection between the peptide stereochemistry and its interaction with the endo-functionalized hosts would be instrumental in designing novel segregation techniques that can be further extended to separate larger model peptides or proteins.