Foldamers are synthetic oligomers that adopt defined secondary structures in solution. The most widely observed foldamer secondary structures are helices. We use all-atom molecular dynamics simulations with improved force field parameters to study these foldamer helices. In this project we present two studies of aromatic foldamer helices: 1) molecular encapsulation; 2) helical unfolding and handedness inversion. 1) Foldamers composed of pyridine and quinoline units have experimentally been shown to form helical capsules and encapsulate small ligands. Some applications of encapsulation are molecular recognition, catalysis and drug delivery. Despite their importance, several molecular level factors determining capsule-ligand stability are missing, such as ligand binding interactions and ligand entering and leaving mechanisms. We find several important factors of consideration in the stability of capsule-ligand complexes including two possible mechanisms of ligand entering and leaving the capsule.2) As well known, helical molecules possess handedness, which affects both their structure and function. Experimental studies have shown the stability of folded conformations and the kinetics of unfolding and handedness inversion in aromatic oligoamides derived from 8-amino-2-quinolinecarboxilic. However, the detailed atomistic picture of helix unfolding and handedness inversion is missing. By using metadynamics method, we obtain the energetics of handedness inversion and demonstrate that to change their handedness, helices do not need to fully unfold but rather a stepwise unfolding of each pitch dihedral in the helix takes place.These studies reveal the crucial atomistic level details in the dynamics and energetics of foldamer helices and help in their rational design.

Computational studies of aromatic foldamer helices: Molecular encapsulation and handedness inversion

248th National Meeting (2014)

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