title: Influence of the ionic liquid [C4mpy][Tf2N] on the structure of the miniprotein Trp-cage.
abstract: We examine 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. We find the ionic liquid has a dramatic effect on Trp-cage, though many similarities with aqueous Trp-cage are observed. We assess Trp-cage folding by monitoring 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, 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. At 365 K, the mobility of the ionic liquid is increased and initial stages of Trp-cage folding are observed, however Trp-cage does not reach the native folded state in 2 μs of simulation in the ionic liquid. Therefore, in addition to conventional molecular dynamics, we also employ scaled molecular dynamics to expedite sampling, and we demonstrate that Trp-cage in the ionic liquid does closely approach the aqueous folded state. Interestingly, while the reduced mobility of the ionic liquid is found to restrict Trp-cage motion, the ionic liquid does facilitate proline cis/trans isomerization events that are not seen in our aqueous simulations.
authors.affiliation: Department of Chemistry, The College of New Jersey, 2000 Pennington Road, Ewing, NJ 08628, United States. Electronic address: bakerj@tcnj.edu.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Baker
authors.affiliation: Department of Chemistry, The College of New Jersey, 2000 Pennington Road, Ewing, NJ 08628, United States.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Furbish
authors.affiliation: Department of Chemistry and Biochemistry, Northern Arizona University, 700 S. Osbourne Drive, Flagstaff, AZ 86011, United States. Electronic address: gerrick.lindberg@nau.edu.
authors.forename: Gerrick E
authors.initials: GE
authors.lastname: Lindberg
mesh_terms: D007094:Imides / Q000737:chemistry*; D052578:Ionic Liquids / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011759:Pyrrolidines / Q000737:chemistry*
chemical_list: C581933:1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide; D007094:Imides; D052578:Ionic Liquids; D010455:Peptides; D011759:Pyrrolidines; C508725:Trp-cage peptide
keywords: Enhanced sampling; Ionic liquids; Molecular dynamics; Protein folding; Trp-cage