Temperature dependence of amino acid hydrophobicities

Abstract

The hydrophobicities of the 20 common amino acids are reflected in their tendencies to appear in interior positions in globular proteins and in deeply buried positions of membrane proteins. To determine whether these relationships might also have been valid in the warm surroundings where life may have originated, we examined the effect of temperature on the hydrophobicities of the amino acids as measured by the equilibrium constants for transfer of their side-chains from neutral solution to cyclohexane (K(w > c)). The hydrophobicities of most amino acids were found to increase with increasing temperature. Because that effect is more pronounced for the more polar amino acids, the numerical range of K(w > c) values decreases with increasing temperature. There are also modest changes in the ordering of the more polar amino acids. However, those changes are such that they would have tended to minimize the otherwise disruptive effects of a changing thermal environment on the evolution of protein structure. Earlier, the genetic code was found to be organized in such a way that--with a single exception (threonine)--the side-chain dichotomy polar/nonpolar matches the nucleic acid base dichotomy purine/pyrimidine at the second position of each coding triplet at 25 °C. That dichotomy is preserved at 100 °C. The accessible surface areas of amino acid side-chains in folded proteins are moderately correlated with hydrophobicity, but when free energies of vapor-to-cyclohexane transfer (corresponding to size) are taken into consideration, a closer relationship becomes apparent.

Keywords: anticodon; genetic code; hydrophophobicity; protein folding; temperature.

Fig. 1.

Hydrophobicities [K_w>c(total)] of amino acid side-chains at 25 °C and 100 °C, colored according to the middle base of the corresponding codon. Changes in the ordering of side-chain hydrophobicities at 25 °C and 100 °C, colored according to the second base of the corresponding codon as indicated. Hydrophobic residues, near the top, tend to be associated with pyrimidines (red and purple), whereas hydrophilic residues, near the bottom, tend to be associated with purines (blue and black).

Fig. 2.

Correlations between amino acid properties and their behavior in folded proteins. (A) Predictions of the logarithm of the distribution constant (K_Surf), derived from the exposed surface area of amino acids in folded proteins based on distribution coefficients of their side-chains. Rose-colored ellipses denote 95% of the area necessary to include all points in the scatterplots. Squared correlation coefficients are given above the scattergrams. (B) Vapor phase analysis of amino acid transfer free energies (4). Colored lines indicate pairs of values used to calculate log K_Surf, according to the background colors in C. (C) Scatterplots between observed values of log K_Surf and values calculated using the three independent pairs of experimental phase transfer free energies in B, two at a time, along with their synergistic interaction (Eq. 3). These correlations average R² = 0.9, whereas those in A average R² = 0.4. Correlations between estimates based on each pair of vapor phase cycle values (panels with white background), average 0.95.