Using Molecular Simulation to Study Biocatalysis in Ionic Liquids

The practice of computational biocatalysis in ionic liquids (ILs) is still in its infancy, and thus best simulation practices are still developing. Herein, we examine the computational and experimental literature to date featuring systems of enzymes in aqueous and neat ILs. The many different approaches taken to parameterize ILs and set up simulations of enzymes in ILs are discussed, and common analysis techniques are reviewed. We also shed light on potential drawbacks and limitations to simulating enzymes in ILs, which include a lack of experimental data with which to validate computational models and inadequate sampling arising from the slow dynamics of many ILs that can lead to inaccurate descriptions of transport and equilibrium thermodynamic properties. A small case study illustrates the effects of scaling IL partial charges, which is a common practice in the field, on the conformational transitions of alanine dipeptide. The degree of charge scaling has a significant effect on the transition times between states of the biomolecule and highlights the importance of carefully setting up systems of enzymes in ILs. Finally, we discuss means to overcome these challenges and briefly consider possible new directions for the field.