We present here molecular dynamics (MD) studies on the handedness induction and molecular encapsulation of the helical arylamide foldamer systems. The current work builds on our recently completed development of an appropriate MD simulation protocol that allows accurate prediction of structures and solution dynamics, as well as handedness inversion mechanism of arylamide foldamers. First, we studied the mechanism of handedness induction in quinoline oligoamides, caused by attaching a chiral group at either the C- or N-terminus. Using the experimentally verified chiral induction groups, we show that free energy profiles of the inversion pathway, obtained by metadynamics simulations, can be utilized to accurately predict the preferred helix handedness. In addition, analysis of conformers with opposite handedness reveals structural and energetics differences between the preferred and non-favoured handed helices. This study provides insight into the folding process of arylamide helices, which can inform and facilitate the rational design of functional foldamers. Second, we show that MD simulations coupled with a simulated annealing scheme provide a design tool for novel arylamide helical structures that encapsulate sugar alcohols. The results indicate promising potential of our computational approach in aiding the design of arylamide foldamers as selective receptors for carbohydrates.

Computational investigations of functional arylamide foldamers

253rd National Meeting (2017)

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