Implications of thermodynamics of protein folding for evolution of primary sequences

• Published in: Nature (London) Vol. 346; no. 6286; pp. 773 - 775
• Main Authors: Shakhnovich, E. I, Gutin, A. M
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 23-08-1990
• Subjects: Amino Acid Sequence; Biological Evolution; Critical temperature; Energy; Evolution; Free energy; Investigations; Mathematics; Models, Theoretical; Probability; Probability distribution; Protein Conformation; Protein folding; Proteins; Spin glasses; Statistical analysis; Temperature; Temperature effects; Thermodynamics; France
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/346773a0

Natural proteins exhibit essentially two-state thermodynamics, with one stable fold that dominates thermodynamically over a vast number of possible folds, a number that increases exponentially with the size of the protein. Here we address the question of whether this feature of proteins is a rare property selected by evolution or whether it is in fact true of a significant proportion of all possible protein sequences. Using statistical procedures developed to study spin glasses, we show that, given certain assumptions, the probability that a randomly synthesized protein chain will have a dominant fold (which is the global minimum of free energy) is a function of temperature, and that below a critical temperature the probability rapidly increases as the temperature decreases. Our results suggest that a significant proportion of all possible protein sequences could have a thermodynamically dominant fold.