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A hydrophobic substance is readily soluble in nonpolar solvents but only sparingly soluble in water (1). They hydrophobic effect is believed to play a major role in organizing the self-assembly of water-soluble, globular proteins (1-4). Upon folding, residues with non-polar side chains that are driven from water will comprise a molecular interior where they can be shielded from solvent access. The effect is analogous to the segregation of oil in water, with the important distinction that residues in proteins are covalently bound to their chain neighbors and cannot partition independently. To quantitate this effect, many scales of hydrophobicity for the amino acids, their residues, and their analogs have been proposed (1-5). Such scales can be classified as solution measurements, empirical calculations, or some combination of the two. Solution scales are based on distribution coefficients between an aqueous phase and a suitably chosen organic phase, while empirical scales are based on partitioning between the solvent accessible surface and the buried interior in proteins of known structure. Significant differences exist among scales. Residues that are strongly hydrophobic on one scale may appear to be strongly hydrophilic on some other scale. For example, in solution measurements, Nozaki and Tanford (1) find tryptophan and tyrosine to be very hydrophobic, while Wolfenden and co-workers (2) find these residues to be very hydrophilic. Scales are compared and their differences have been discussed (6). We now derive two new scales that are based on accessibility to solvent for residues within proteins of known structure. These scales measure two quantitites that can be distinguished: 1) The area lost when a residue is transferred from a defined standard state to a folded protein. The area a residue buries upon folding is proportional to its hydrophobic contribution to the conformational free energy, [DELTA]G.sub.conf (7). 2) The fractional accessibility of a residue, defined as its mean accessible area in protein molecules divided by the standard state area. The fractional accessibility is an intrinsic measure of hydrophobicity. Although related, these quantities are not equivalent. For example, a bulky arginine residue makes a large hydrophobic contribution to [DELTA]G.sub.conf because its area loss upon folding is large, approximating that of leucine. Yet, the fractional accessibility of an arginine is comparatively high because the remaining unburied area is also large. In his influential review (8), Kauzmann used model compounds to show that burial of hydrophobic groups is a significant source of stabilization energy in proteins. More than a decade later, analysis of x-ray elucidated proteins disclosed that many hydrophobic groups remain unburied (3-4, 9). Summarizing these findings, Richards wrote (7): Of the accessible areas of native structures, roughly half represents polar atoms and half nonpolar atoms. Thus the 'grease' is by no means all 'buried'. In the folding process there are roughly equivalent decreases in the accessibility of both the polar and nonpolar groups. The relevant forces and the final structure require more careful definition than is implied by the common feeling that inside equals nonpolar and outside equals polar. Subsequent studies revealed further complexity:...
Source Citation (MLA 8 th Edition)
Rose, George D., et al. "Hydrophobicity of amino acid residues in globular proteins." Science, vol. 229, 1985, p. 834+. Academic OneFile, Accessed 16 Jan. 2018.
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