Room temperature ionic liquids (ILs) are known to have a variety of applications in biological systems due to their highly tunable physical and chemical properties. However, the number of possible cations and anions that can be used in ILs also presents a challenge in that the selection of a specific IL for a desired application typically involves a guess-and-check approach. Here we present the results of microseconds of all-atom molecular dynamics simulations of the small, fast-folding miniprotein Trp-cage in 13 different ILs, in order to develop an atomistic understanding of how the molecular characteristics of a cation/anion pair can influence protein structural stability. Trp-cage was chosen because it has been extensively studied computationally, and is quite stable under standard conditions in aqueous solution. For this work we chose four cations ([BMIM], [EMIM], [CHO] and [TMA]) and three anions ([Cl-], [DCA] and [Tf2N]) from which we constructed all possible IL combinations and simulated all twelve permutations. We also studied the IL [C4mpy][Tf2N] because our group has simulated Trp-cage in this ionic liquid in the past. Thirteen 1 µs simulations of the folded Trp-cage protein in low concentration IL were conducted, in addition to a control simulation of Trp-cage in water. The stability of Trp-cage was assessed by analyzing various structural qualities of Trp-Cage, including the root mean squared deviation of the Trp-cage backbone atoms, secondary structure, the radius of gyration and distances between key residues in the protein. Our initial results indicate that the ILs [BMIM][Tf2N], [EMIM][Cl-], [TMA][DCA] and [C4mpy][Tf2N], have larger destabilizing effects on Trp-cage structure than the other ILs, where the behavior of Trp-cage resembles that observed in water. Finally, we calculated the radial distribution functions for cations and anions to each residue in Trp-cage to investigate how IL components associate with the protein. From this analysis, we found that ILs containing the anions [Tf2N] and [DCA] more closely approached Trp-cage residues than the cations.

Investigating the influence of low concentration ionic liquids on Trp-cage structural stability

254th National Meeting (2017)

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