Published March 28, 2016 | Version v1
Journal article

Effects of monohydric alcohols and polyols on the thermal stability of a protein

  • 1. Graduate School of Energy Science, Kyoto University, Uji, Kyoto 611-0011 (Japan)
  • 2. Institute of Advanced Energy, Kyoto University, Uji, Kyoto 611-0011 (Japan)

Description

The thermal stability of a protein is lowered by the addition of a monohydric alcohol, and this effect becomes larger as the size of hydrophobic group in an alcohol molecule increases. By contrast, it is enhanced by the addition of a polyol possessing two or more hydroxyl groups per molecule, and this effect becomes larger as the number of hydroxyl groups increases. Here, we show that all of these experimental observations can be reproduced even in a quantitative sense by rigid-body models focused on the entropic effect originating from the translational displacement of solvent molecules. The solvent is either pure water or water-cosolvent solution. Three monohydric alcohols and five polyols are considered as cosolvents. In the rigid-body models, a protein is a fused hard spheres accounting for the polyatomic structure in the atomic detail, and the solvent is formed by hard spheres or a binary mixture of hard spheres with different diameters. The effective diameter of cosolvent molecules and the packing fractions of water and cosolvent, which are crucially important parameters, are carefully estimated using the experimental data of properties such as the density of solid crystal of cosolvent, parameters in the pertinent cosolvent-cosolvent interaction potential, and density of water-cosolvent solution. We employ the morphometric approach combined with the integral equation theory, which is best suited to the physical interpretation of the calculation result. It is argued that the degree of solvent crowding in the bulk is the key factor. When it is made more serious by the cosolvent addition, the solvent-entropy gain upon protein folding is magnified, leading to the enhanced thermal stability. When it is made less serious, the opposite is true. The mechanism of the effects of monohydric alcohols and polyols is physically the same as that of sugars. However, when the rigid-body models are employed for the effect of urea, its addition is predicted to enhance the thermal stability, which conflicts with the experimental fact. We then propose, as two essential factors, not only the solvent-entropy gain but also the loss of protein-solvent interaction energy upon protein folding. The competition of changes in these two factors induced by the cosolvent addition determines the thermal-stability change.

Additional details

Identifiers

Publishing Information

Journal Title
Journal of Chemical Physics
Journal Volume
144
Journal Issue
12
Journal Page Range
p. 125105-125105.10
ISSN
0021-9606
CODEN
JCPSA6

INIS

Country of Publication
United States
Country of Input or Organization
International Atomic Energy Agency (IAEA)
INIS RN
49002983
Subject category
S37: INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL CHEMISTRY;
Resource subtype / Literary indicator
Numerical Data
Descriptors DEI
ALCOHOLS; BINARY MIXTURES; EXPERIMENTAL DATA; INTEGRAL EQUATIONS; MOLECULES; PROTEINS; SOLVENTS
Descriptors DEC
DATA; DISPERSIONS; EQUATIONS; HYDROXY COMPOUNDS; INFORMATION; MIXTURES; NUMERICAL DATA; ORGANIC COMPOUNDS

Optional Information

Notes
(c) 2016 AIP Publishing LLC