Protein structure, stability and solubility in water and other solvents

• Published in: Philosophical transactions of the Royal Society of London. Series B. Biological sciences Vol. 359; no. 1448; pp. 1225 - 1235
• Main Authors: Nick Pace, C., Treviño, Saul, Prabhakaran, Erode, Martin Scholtz, J.
• Format: Journal Article
• Language: English
• Published: England The Royal Society 29-08-2004
• Subjects: Biochemistry; Cyclohexanes - metabolism; Entropy; Ethanol; Ethanol - metabolism; Hydrogen; Hydrogen Bonding; Hydrogen Bonds; Hydrophobic Bonds; Models, Chemical; Molecules; Protein Conformation; Protein Folding; Protein Solubility; Protein Stability; Protein Structure; Proteins - chemistry; Proteins - metabolism; Solubility; Solvents; Solvents - chemistry; Vacuum; Water - metabolism
• ISSN: 0962-8436; 1471-2970
• DOI: 10.1098/rstb.2004.1500

Proteins carry out the most difficult tasks in living cells. They do so by interacting specifically with other molecules. This requires that they fold to a unique, globular conformation that is only marginally more stable than the large ensemble of unfolded states. The folded state is stabilized mainly by the burial and tight packing of over 80% of the peptide groups and non-polar side chains. If life as we know it is to exist in a solvent other than water, the folded state must be stable and soluble in the new solvent. Our analysis suggests that proteins will be unstable in most polar solvents such as ethanol, extremely stable in non-polar solvents such as cyclohexane, and even more stable in a vacuum. Our solubility studies suggest that protein solubility will be markedly lower in polar solvents such as ethanol and that proteins will be essentially insoluble in non-polar solvents such as cyclohexane. For these and other reasons it seems unlikely that the life we know could exist in any solvent system other than water.