We have examined the effect of the ionic liquid [C4mpy][Tf2N] on the structure of the miniprotein Trp-cage and contrast these results with the behavior of Trp-cage in water. While similarities are observed between Trp-cage in water and the ionic liquid, we find that the ionic liquid has a dramatic effect on Trp-cage structure. Trp-cage folding is monitored using a number of metrics including root mean square deviation from the crystallographic structure, radius of gyration, proline cis/trans isomerization state, protein secondary structure, amino acid contact formation and distance, and native and non-native contact formation. Starting from an unfolded configuration, we observe that Trp-cage folds in water at 298 K in less than 500 ns of simulation, but has very little mobility in the ionic liquid at the same temperature, which can be ascribed to the higher ionic liquid viscosity. In simulations at 365 K, the mobility of the ionic liquid is increased and we are able to observe initial stages of Trp-cage folding in our simulations. However, Trp-cage still does not reach the native folded state in 2 μs of simulation in the ionic liquid even at this higher temperature. Therefore, in addition to conventional molecular dynamics, we also employ scaled molecular dynamics to expedite sampling, demonstrating that Trp-cage in the ionic liquid can approach the aqueous folded state. Interestingly, while the reduced mobility of the ionic liquid is found to restrict Trp-cage motion, we observe that proline cis-trans isomerization events that are not seen in our aqueous simulations at 298 K or 365 K are facilitated in the ionic liquid at 365 K.

Probing the influence of the ionic liquid [C4mpy][Tf2N] on the structure of the miniprotein Trp-cage

251st National Meeting (2016)

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