Effect of an ionic liquid/air Interface on the structure and dynamics of amphiphilic peptides

Ionic liquids (ILs) are well known to have significant impacts on the structure and dynamics of proteins and enzymes; however, there is still much to be done to understand the molecular scale mechanisms of these processes. Using classical molecular dynamics (MD) and metadynamics simulations, we have studied how multiple IL solutions change the structure and behavior of two short, model, leucine-lysine (LK) peptides at a vacuum/solvent interface. These peptides - LKα14 and LKβ15 - have been researched extensively through both experiments and simulations in pure water, but have not yet been examined when exposed to ILs. In our study, we found that the two 50% 1-butyl-3-methylimidazolium ([BMIM])-based solutions we tested had a substantial effect on both the interfacial adsorption affinity and secondary structure of our peptides when compared to water. Metadynamics simulations revealed a nearly 40 kJ/mol difference in interfacial adsorption free energy for the same peptide when solvated in water versus in IL solution. Additionally, we saw IL solutions prevent LKβ15 from forming extended β-sheet structures that were found to form at the vacuum/water interface. In place of these β-sheet structures, we observed the formation of a structure similar to a left-handed helix for lone LKβ15 peptides at the interface. The presence of IL also had a subtle effect on LKα14's strong α-helical character, reducing it for peptides at the interface and increasing it for peptides in bulk solution. This work provides several new testable hypotheses about IL action on biomolecular structure that can be studied in detail using experimental surface-specific analysis techniques such as sum frequency generation (SFG) spectroscopy.