Biophysics and Physicobiology

The Biophysical Society of Japan.

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10th Biophysics and Physicobiology Award

Koji Oda, Masahiro Kinoshita
"Physicochemical origin of high correlation between thermal stability of a protein and its packing efficiency: a theoretical study for staphylococcal nuclease mutants"
Biophysics and Physicobiology, Vol.12, pp.1-12 (2015).

Reason for the Award

There is an empirical rule that the thermal stability of a protein is related to the packing efficiency or core volume of the folded state and the protein tends to exhibit higher stability as the backbone and side chains are more closely packed. In this paper, based on statistical thermodynamics, the authors showed that the pivotal factor to determine the thermal stability is the magnitude of the water-entropy gain upon folding by examination of the thermal-stability change upon various mutations of staphylococcal nuclease using the X-ray crystal structures of the wild-type and the mutants. The authors also evaluated the empirical rules, and they disagree that a traditionally accepted concept that the intramolecular van der Waals interaction energy is an essential factor governing the protein stability against heating. Because of the generality of their theory, the cold, pressure, and thermal denaturation can also be elucidated by their theoretical method. As the authors describe in the article, they extend the Asakura-Oosawa theory, which, in 1954, considered only the excluded-volume term of the pair correlation between a large particle and small ones using simple continuum models. Based on the physical essence of the Asakura-Oosawa theory, the authors construct their theory for proteins having arbitrary shapes with atomic resolution, including the many-body correlations between a protein and water molecules.
Thus, this article provides an important conceptual progress to understand the thermal stability of proteins and the folding mechanism. In fact, their theory has been further applied to many different systems including GPCR membrane proteins.

July, 2021
Biophysics and Physicobiology Award Selection Committee


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