|A protein molecule equation overlay method on a 2012 textbook on the thermodynamics and kinetics of protein, RNA, and DNA. |
Protein was discovered in 1838 by Dutch chemist Gerardus Mulder who carried out elemental analysis of common proteins and found that nearly all proteins had the same empirical formula, C400H620N100O120P1S1.
This discovery was said to have sparked a heated debate between the so-called difference between "animal life" and "plant life" (vegetable life).
The general subject of the thermodynamics of protein folding seems to revolve around the circa 1955 "thermodynamic hypothesis" (Anfinsen’s dogma) positioned by American biochemist Christian Anfinsen to explain protein folding; loosely, that the "native structure" is a unique, stable and kinetically accessible minimum of the free energy. Anfinsen won half the 1972 Nobel Prize in chemistry for this hypothesis. 
Computer methods | Levinthal paradox
In the late 1960s, American physicist Cyrus Levinthal (1922-1990) pioneered the use computers to represent folded protein molecules in three dimensions, and to use computational methods to predict the 3-dimensional structure of proteins. 
His famous 1969 paper “How to Fold Graciously”, outlined a sort of counting objection to the thermodynamic hypothesis, namely that the speed observed in actual protein foldings (less than one second or less) does not match up with the time predicted by the thermodynamic hypothesis (10 billion years). 
Levinthal’s paper thus introduced what has come to be known as the “Levinthal paradox”, the now classical viewpoint of protein folding that proteins cannot fold by a random search for the native (correctly folded) state because this would take far too long, and must therefore fold via a sequential (free energy intermediate states), energy biased folding pathway. 
Free energy landscapes
See main: Free energy landscapes; Free energy map; Potential energy surfaceThe quick and short view of the thermodynamics of proteins is that a protein is considered “active” when it is folded in a well-defined three-dimensional conformation called the “native state”. The folding process is considered a spontaneous one correlative to a decrease in the change in the Gibbs free energy ΔG for the process, such that the native state is believed to be a minimal free energy among those available to the protein chain. It is reasoned that the stability of the folded state arises from a balance between what is called “chain entropy” loss and the gain in what is called “effective energy”, which takes into account the effect of the solvent. To validate this view, one needs to have a well correlated “energy landscape” (free energy map), such that alternative folded states of high energy exist as compared to the lower free energy of the native state. 
|Manuscripts published per year reporting thermodynamic quantities on protein folding and stability.|
The subject of thermodynamics applied to protein movements begun take of in 1960s and 70s. The chart below shows the annual number of publications reporting experimentally determined thermodynamic quantities on protein folding and stability. 
In 1993, American biophysicist Donald Haynie completed his PhD on the thermodynamics of protein folding; later writing one of the first biological thermodynamics textbooks themed on this topic.
1. Pfeil, Wolfgang. (2001). Protein Stability and Folding: A Collection of Thermodynamics Data (pg. 3). Springer.
2. Protein thermodynamics – University of Madrid.
3. Anfinsen, Christian B. (1972). “Studies on the Principles that Govern the Folding of Protein Chains.” Nobel Lecture, Dec. 11.
4. (a) Levinthal’s paradox – Wikipedia.
(b) Cyrus Levinthal – Wikipedia.
5. Faisca, Patricia F.N. (2007). “Shaping Protein Folding Dynamics with Native State’s Geometry”, in: Soft Condensed Matter (pgs. 196-97), Kathy I. Dillon, editor. Nova Publishers.
6. (a) Levinthal, Cyrus. (1969). “How to Fold Graciously”, Mossbauer Spectroscopy in Biological Systems: Proceedings of a meeting held at Allerton House, Monticello, Illinois: 22–24.
(b) Brooks, Charles L., Onuchic, Jose N., and Wales, David J. (2001). “Statistical Thermodynamics: Taking a Walk on a Landscape”, Science, 293(5530):612-13.
7. Kuriyan, John, Konforti, Boyana, and Wemmer, David. (2012). The Molecules of Life: Physical and Chemical Principles (GB). Garland Science.
● Oosawa, Fumio and Asakura, Sho. (1975). Thermodynamics of Polymerization of Protine. Academic Press Inc.
● Brooks, Charles L., Karplus, Martin, and Pettittt, B.M. (1990). Proteins: a Theoretical Perspective of Dynamics, Structure, and Thermodynamics (ch. 2: Potential Functions, pgs. 23-32; ch. 5: Thermodynamic Methods, pgs. 59-74; ch. 10: Thermodynamic Aspects, pgs. 175-90). John Wiley and Sons.
● Koliński, Andrzej and Skolnick, Jeffrey. (1996). Lattice Models of Protein Folding, Dynamics, and Thermodynamics. Chapman & Hall.
● Cooper, Alan. (1999). “Thermodynamics of Protein Folding and Stability” (48-pgs) (PDF), pre-print. JAI Press Inc.
● Goldstein, Richard A. (2004). “Evolutionary Perspectives on Protein Thermodynamics”, in Comutational Science: ICCS 2004, (pgs. 718-27). Springer.
● Anon. (2007). “How does Entropy Affect Protein Folding?” (Ѻ), Pande Lab Science, Stanford, Aug 14.
● The Thermodynamics of Protein Unfolding – Stephen Mulcahy.
● Protein thermodynamics – Editor’s Summary, Nature, 14 July 2007.
● Hauryliuk, Vasili. (2011). “Darwin meets Gibbs: making a temperature-resistant protein”, Jan 17, Stringent Response, Blogspot.com.