Vinicius PICCOLI1, Leandro MARTÍNEZ1
1UNICAMP, CAMPINAS, Brazil
Ionic liquids (ILs) are solvents whose physicochemical features are attracting increasing interest for academic and industrial applications. Despite the growing number of studies employing ionic liquids, their interactions in many systems, particularly biotechnological ones, remain poorly understood. This lack of prediction on how ILs will interact with complex molecules is due to the chemical and structural complexity of both substances.
Using Molecular Dynamics (MD) simulations of systems containing the protein Ubiquitin, water, and several ionic liquids, we examine the impact of common ions and multiple electrolytes on protein solvation by ILs. For each concentration (ranging from 0.5 to 3.0 mol L-1), 20 production simulations of 10 ns were undertaken to ensure that the Kirkwood-Buff (KB) integrals converged properly. The simulated ILs were constituted of 1-ethyl-3-methylimidazolium (EMIM), and the anions dicyanamide (DCA), nitrate (NO3), tetrafluoroborate (BF4), and Chloride (Cl). The solvation structure was investigated by calculating minimum-distance distribution functions (MDDFs) and applying the KB theory. Using time-correlation functions, the dynamic behavior of the ions was analyzed to obtain a clear image of the influence of the ions on other dynamics.
The examination of MDDFs in systems with only one IL demonstrates that the simulated anions, particularly DCA and NO3, tend to accumulate near the protein surface ( at ~1.9 Å). Considering the four simulated anions, the primary reason for this is the strong capacity of DCA and NO3 to form hydrogen bonds (specific interactions) with the protein surface atoms. Additionally, in the case of DCA, non-specific interactions with neutral protein residues play a significant role in the accumulation of DCA. The cation, on the other hand, tends to concentrate at ~2.4 Å due primarily to non-specific interactions. In the system containing EMIMCl + EMIMDCA, DCA exhibits huge accumulations at ~1.9 Å and ~2.6 Å, whereas EMIM exhibits a large peak at ~2.4 Å and a second, much smaller peak at ~5.0 Å. Chloride, have a peak at ~2.0 Å (much smaller than those from DCA), and a succession of successive accumulation peaks, with the highlight to one at 4.0 Å. The decomposition in solute contributions demonstrates that the anions interact predominantly with polar and basic residues (~1.9 Å), while in the second peak (~2.6 Å) the anions interactions are more associated with neutral residues. The total ionic accumulation in the protein domain is highly dependent on an ion that can strongly be concentrated in the protein domain.
The time-correlation functions also demonstrated that the presence of DCA considerably altered the residence time of ions in systems containing a mixture of ILs within 3.5 Å of the protein surface. For example, the chloride residence time with EMIMCl is significantly higher than in systems with EMIMCl + EMIMDCA, because DCA spends more time in the first solvation shells. Thus, the interactions between the ions and the protein are crucial to dictate the ionic accumulation in the protein domain.