Challenge on theoretical assessment of a hypothesis on protein folding stability that has been widely believed for 60 years ~The protein intramolecular interactions are suggested as the driving force of protein folding~


Theoretical physical chemistry group from Research Institute for Interdisciplinary Science, Okayama University (Dr. T. Sumi and Prof. K. Koga) developed a computational method to extract the dominant factor of protein folding stability and applied it to a design protein chignolin. On the basis of the results on the free-energy decomposition obtained for chignolin, they derived a simple conclusion that is qualitatively different from the widely accepted theory of protein stability “the hydrophobic interaction hypothesis” that has been believed for 60 years: the driving force of protein folding is attributed to the protein intramolecular interactions rather than the solvent-mediated forces.

In the hydrophobic interaction hypothesis, as according with the oil and water separation phenomena, the thermodynamic stability of proteins is generally interpreted via the solvent-mediated forces due to water's dislike to oil. However, the solvent-mediated interactions basically tend to mixing oil (hydrophobic residues) and water and the driving forces of protein folding is rather attributable to the intramolecular direct interactions including the London van der Waals forces acting between all amino acid residues. The results obtained for chignolin suggests the necessity to reconsider this hypothesis that has been believed for the long time. These results provide insights into a design strategy of artificial proteins and developments of new biopharmaceuticals.

Research article
Tomonari Sumi and Kenichiro Koga
Theoretical analysis on thermodynamic stability of chignolin
Scientific Reports 9, 5186 (2019).

DOI: 10.1038/s41598-019-41518-1

Theoretical Physical Chemistry Lab