Influence of an ionic liquid on the conformational sampling of Xaa-Pro dipeptides

Room temperature ionic liquids have demonstrated promise for the selective control of protein structure and function, but fundamental aspects of ionic liquid effects on peptides and proteins remain unclear. In this study molecular dynamics simulations are used to understand the effect of the room temperature ionic liquid 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl) imide ([C₄mpy][Tf₂N]) on the behavior of Xaa-Pro dipeptides, where Xaa is any of the common amino acids, at several temperatures and compared to water, octanol, and vacuum. Generally, compared to water and octanol, the room temperature ionic liquid is found to restrict peptide conformational sampling, which results in narrower radius of gyration distributions and area visited in Ramachandran space. Despite the restricting effects of [C₄mpy][Tf₂N], it is found to result in isomerization of the Trp-Pro dipeptide bond to the cis state at 298 K, suggesting that this ionic liquid can be used to stabilize otherwise infrequently observed dipeptide conformations. Our simulations suggest that stacking of the Trp ring and Pro ring in the cis state versus the trans state contribute to this effect for the Trp-Pro dipeptide. When the temperature of the ionic liquid system is increased, the viscosity of the solvent decreases and the area sampled by the dipeptide in Ramachandran space becomes more similar to water, octanol, and vacuum environments.