Send Orders for Reprints to reprints@benthamscience.net Current Biochemical Engineering, 2014, 1, -0 1 Thermodynamic Contribution of Amino Acids in Ionic Liquids Towards Protein Stability Awanish Kumar a , Pannuru Venkatesu a, *, Mohamed Taha b and Ming-Jer Lee b a Department of Chemistry, University of Delhi, Delhi-110 007, India; b Department of Chemical Engineering, National Taiwan University of Science and Technology, 43 Keelung Road, Section 4, Taipei 106-07, Taiwan Abstract: Amino acids (AA s ) 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 AA s in a pro- tein backbone is only responsible for the individual characteristics of the macromolecule. The AA s 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 AA s in various solvents and co-solvents. A basic level of quantifying protein-solvent interactions involve the use of transfer free energies, G tr from water to solvents. The values of G tr for side chains and peptide backbone quantify the thermodynamic consequences of solvating a protein species in a co-solvent solution rela- tive to pure water. Based on the transfer model and experimental G tr for these AA s , it has been proposed that these co- solvents exert their effect on protein stability primarily via the protein backbone. The G tr of AA s from water to another solvent system will be either favorable or unfavorable. By definition, an unfavorable transfer free energy, G tr > 0, means that the protein becomes solvophobic on transfer to a solvent, whereas a favorable transfer free energy, G tr < 0, repre- sents that the protein becomes solvophilic on transfer to a solvent. The sign and magnitude of the measured G tr 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. Keywords: Amino acids, free energy, ionic liquids, molecular dynamics, protein stability, thermodynamics. 1. INTRODUCTION The co-valent structure of a natural protein molecule is primarily because of the 20 different amino acids (AA s ). These AA s are the building blocks that differ in size, shape, charge, hydrogen-bonding capacity, hydrophobicity and chemical reactivity. The polar or charged AA s participate in hydrogen bonding and electrostatic interactions, with co- solvents or solvent itself. On the other hand non-polar AA s have unfavorable interactions with the solvent molecules (especially water). Clustering of these hydrophobic AA s in the interior of the protein provides a thermodynamic driving force for protein folding (the hydrophobic effect). Both these interactions of the AA sequence spontaneously and selec- tively give rise to a unique protein structure that is an attrac- tive aspect of the structural features in a biomolecule [1]. Basically, the nature and the arrangement of the AA side- chain in a protein backbone is responsible for the biophysical properties of the macromolecule and it has been recognized in the open literature that all of the information pertaining to protein can be obtained through investigating the properties of the AA sequence [1, 2]. Moreover, proteins differ from *Address correspondence to this author at the Department of Chemistry, University of Delhi, Delhi-110 007, India; Tel: +91-11-27666646-142; Fax: +91-11-2766 6605; E-mails: venkatesup@hotmail.com; pvenkatesu@chemistry.du.ac.in each other (in physical properties/functions) due to the varia- tions in AA s sequence. Basically, the disulphide bridges are influenced by the aqueous solutions in the protein backbone hence, it is crucial to have an initiative in understanding the solubility, stability, and bio-thermodynamic properties of AA s in aqueous solutions [3, 4]. Theoretical and computer simulation studies on the thermodynamic properties of AA s and the role of electrostatics in particular, in this context, become very important in developing a molecular view of how different residues interact with each other and with sol- vent and an ion atmosphere [5-7]. Most of the proteins found in nature have to adopt a spe- cific three dimensional conformation, called folded or native state for proper functioning. Considering the vital impor- tance of proteins in living organisms, the investigation of the structural and functional properties of proteins has been al- ways a priority with biochemists. A challenging and rapidly emerging field of biotechnology is the tailoring of proteins to carry out unique functions at different physiological and process conditions. Protein folding is of particular concern in the production of industrial biocatalysts as well as for storage purpose, where the enzymes are often inactive due to mis- folding. Protein folding is a reversible transition state of a protein composed of AA residues that is in rapid equilibrium between its ordered and disordered states. This equilibrium between the folded and the unfolded states of the protein can 2212-7127/14 $58.00+.00 © 2014 Bentham Science Publishers