Water, Protein Folding, and the Genetic Code

Abstract

The absolute affinities of amino acid side chains for solvent water closely match their relative distributions between the surface and the interior of native proteins and are associated with a remarkable bias in the genetic code.

Studying membrane proteins through the eyes of the genetic code revealed a strong uracil bias in their coding mRNAs

“…9), various explanations of its organization and the assignment of the 64 triplets have been offered (10,11). It was soon realized that chemically similar amino acids are often encoded by relatively similar codons (12,13) and that very hydrophobic amino acids are encoded by codons having uracil (U) in the second position (14). Our analysis revealed that, in addition to their second position, codons of very hydrophobic amino acids have a remarkably high U content in general (Fig.…”

A simple method for displaying the hydropathic character of a protein

“…This difficulty has been noted in the past, and it has been suggested that water-vapor transfer free energies would be a less complicated index of hydropathy (Hine & Mookerjee, 1975). The watervapor partition coefficients for model compounds identical to each of 14 amino acid sidechains were assembled by Wolfenden et al (1979Wolfenden et al ( ,1981 from the Tables published by Hine & Mookerjee (1975). They reported as well experimental determinations for four additional.…”

“…They reported as well experimental determinations for four additional. previously unavailable, values (Wolfenden et al, 1979). All of these values, expressed as transfer free energies between an aqueous solution and the condensed vaport.…”

Temperature dependence of amino acid hydrophobicities

“…Early work on the crystal structure of hemoglobin and related proteins showed that the side-chains of the more polar amino acid residues tend to be exposed to solvent, whereas less polar side-chains tend to be buried within the interior of globular proteins (1). Later, those tendencies were put to a quantitative test by measuring equilibria of transfer of amino acid side-chains from neutral aqueous solution into less polar environments, such as the vapor phase (2,3) or a nonpolar solvent such as cyclohexane (4), which dissolves only ∼2 × 10 −3 M water at saturation (5) and appears to be devoid of specific interactions with solutes. The water-to-cyclohexane distribution coefficients (K w>c ) of the 20 common sidechains [here termed "hydrophobicities" (6, 7) and expressed in concentration units of mol/L in each phase; SI Appendix] were found to span a range of 15 orders of magnitude at pH 7 and 25°C.…”

“…Thus, a pyrimidine at the second codon position signals amino acids whose average hydrophobicity is much greater than those coded by a purine at the same position (2,3). The values reported here allow a more detailed analysis, described in a companion paper (16), which reveals that two separate codes for amino acid size and hydrophobicity appear to be embedded in different parts of their tRNA sequences, with size (represented by vapor-to-cyclohexane equilibria) encoded in the acceptor stem, and hydrophobicity (represented by water-to-cyclohexane equilibria) embedded in the anticodon.…”