Thermodynamic Contribution of Amino Acids in Ionic Liquids Towards Protein Stability

Amino acids (AAs) combine to form a three-dimensional protein structure and are of very much importance in understanding the biophysical properties of biomolecules. Basically, the nature and the arrangement of the AAs in a protein backbone is only responsible for the individual characteristics of the macromolecule. The AAs in a protein backbone are influenced by the solvent molecules hence, it is very important to have a clear idea on the solubility, stability, and thermodynamic properties of these AAs in various solvents and co-solvents. A basic level of quantifying protein-solvent interactions involve the use of transfer free energies, ΔGtr from water to solvents. The values of ΔGtr for side chains and peptide backbone quantify the thermodynamic consequences of solvating a protein species in a co-solvent solution relative to pure water. Based on the transfer model and experimental ΔGtr for these AAs, it has been proposed that these cosolvents exert their effect on protein stability primarily via the protein backbone. The ΔGtr of AAs from water to another solvent system will be either favorable or unfavorable. By definition, an unfavorable transfer free energy, ΔGtr > 0, means that the protein becomes solvophobic on transfer to a solvent, whereas a favorable transfer free energy, ΔGtr < 0, represents that the protein becomes solvophilic on transfer to a solvent. The sign and magnitude of the measured ΔGtr quantifies the protein response to changes in solvent quality. Therefore, this review will provide the basis of a universal mechanism for co-solvent-mediated (that includes the new novel biocompatible ionic liquids (ILs)) protein stabilization and destabilization as the protein backbone is shared by all proteins, regardless of side chain sequence.