Hydrophobicity scale amino acid residue

Many scales, either empirical or measured, have been proposed for the hydrophobicity of amino acid residues in proteins (Nakai and Li-Chan, 1988). The most extensive study on tlje hydrophobicity index of amino acids was published by Wilce et al. (1995). The authors derived four new scales of coefficients from the reversed-phase high-performance liquid chromatographic retention data of 1738 peptides and compared them with 12 previously published scales. 

Identical amino acids are often inadequate to identify related proteins or, more importantly, to determine how closely related the proteins are on an evolutionary time scale. A more useful analysis includes a consideration of the chemical properties of substituted amino acids. When amino acid substitutions are found within a protein family, many of the differences may be conservative—that is, an amino acid residue is replaced by a residue having similar chemical properties. For example, a Glu residue may substitute in one family member for the Asp residue found in another both amino acids are negatively charged. Such a conservative substitution should logically garner a higher score in a sequence alignment than does a nonconservative substitution, such as the replacement of the Asp residue with a hydrophobic Phe residue. 

Thien et al. (18) also showed that the degree of solubilisation depends on the relative hydrophobicities of the amino acid residues. A measure of this effect is the slope of the solubilisation curve when replotted as a function of the net solute charge, as shown in Figure 10 for arginine. It was found that this slope correlated well with the hydrophobicity scale proposed by Bull and Breese (1j)), as is evident from Figure 11. It is intriguing to note that the more hydrophobic the residue the greater the solubilisation of the amino acid. This could be due to one of three effects, as discussed below. 

Volume = Volume enclosed by van der Waals radii Mass = molecular weight of nonionized amino acid minus that of water both adopted from Creighton (1993) HP scale = degree of hydrophobicity of amino acid side chains, based on Kyte Doolittle (1982) Surface Area = mean fraction buried, based on Rose et al. (1985) and Secondary structure propensity = the normalized frequencies for each conformation, adopted from Creighton (1993), is the fraction of residues of each amino acid that occurred in that conformation, divided by this fraction for all residues. 

The hydrophobicity profile is a simple way to quantify the concentration of hydrophobic residues along the linear polypeptide chain (Rose Dworkin, 1989). The construction of the profiles depends on the choice of the hydrophobicity scale and the window size. The profile is computed by averaging the hydrophobicity scales of amino acid residues within... 

Using the hydrophobicity scale as an example, the amino acid residues can be represented by the real-numbered scalar value. They can also be classified with respect to their side chains as polar, nonpolar, or amphipathic, depending on the range of the hydrophobicity in the scale, such as in... 

Naray-Szabo, G. and Balogh, T. (1993). The Average Molecular Electrostatic Field as a QSAR Descriptor. 4. Hydrophobicity Scales for Amino Acid Residues Alpha. J.Mol.Struct.(Theo-chem), 103, 243-248. 

Figure 4 shows the hydropathy plots for the L-, M- and H-polypeptides of Rb. sphaeroides R-26, using a moving window of 19 amino-acid residues for each scan. The plots for the L- and M-polypeptides [Fig. 4 (A) and (B)] are very similar, showing that both polypeptides have five hydrophobic segments. Each of these hydrophobic segments contains enough amino acids to form a membrane-spanning a-helix. Note that the residue-number scale strictly applies only to the L- and H-polypeptides that for the M-polypep-tide has been shifted in order to maximize the coincidence of its hydrophobic regions with those of the L-polypeptide. The hydropathy plot for the H-polypeptide [Fig. 4 (C) ] shows that it has only one hydro-phobic region, indicating the presence of just one a-helix. Thus the presence of eleven transmembrane helices in the L-, M- and H-subunits as predicted by hydropathy plots is in accord with conclusions drawn from previous studies by circular dichroism and polarized infrared spectroscopy and later confirmed by X-ray diffraction studies.

In a dilute protein solution, the nano length scale or the molecular structure of protein molecules determines the thermodynamic equilibrium between protein-protein and protein-water interactions. The consequent surface and hydrodynamic properties of proteins are resulted from the proportion of hydrophobic, hydrophilic, and charged amino acid residues. For example, caseins could adopt a random coil structure due to their flexible structure as a result of phosphorylated serine residues caseins indeed lack the ordered structures of a-helix, 3-sheet, and 3-turn found in globular proteins. This gives rise to better multifunctionality of caseins over globular proteins. 

Table 5.1. Tfbased hydrophobicity scale for protein engineering of naturally occurring amino acid residues (in order of more hydrophobic [low TJ to more polar [high T ]). ...

The T,-based Hydrophobicity Scale for Amino Acid Residues... 

Figure 5.9. Experimental data for development of the T,-based hydrophobicity scale. The general composition for the protein-based polymer is poly [f,(GXGVP),fv(GVGVP)], where X is the guest amino acid residue to be evaluated and fx and E are mole fractions wherein fj -i- E = 1. Part A contains the raw data for a number of guest residues substituted at a mole fraction of 0.2, which means 4 substituted residues per 100 residues of poly(GVGVP). The experimental conditions were 40mg/ml of polymer of a molecular weight of about 100,000 Da in 0.15 N NaCl and 0.01 M phosphate at pH 7.4. Experimental T,-values were obtained as shown in part A for fx = 0.2, and additional polymers were characterized with different fx values such that a plot of fx versus T, could be constructed as in part B. Extrapolation of the linear plots in part B to fx = 1 gave the T,-values that became the basis for the T,-based hydrophobicity scale given in Table 5.1. (Adapted with permission from Urry. )...

The relative oil-like character of each amino acid residue is given in terms of the Tt-based hydrophobicity scale in Table 5.1. T, is measured by plotting as indicated in Figure 5.9 and the technical term for oil-like, hydrophobic (meaning water fearing), is used. The more commonly used technical term, hydrophobicity, replaces the equivalent statement of oil-like character. 

Table 5.3. Hydrophobicity Scale in terms of AGha, the change in Gibbs free energy for hydrophobic association, for amino acid residue (X) of chemically synthesized poly[fv(GVGVP), fx(GXGVP)], 40m ml, mw = 100 kDa in 0.15 N NaCl, 0.01 M phosphate, using the net heat of the inverse temperature transition, AGha = [AH,(GGGVP) - AH.(GXGVP)] for the fx = 0.2 data extrapolated to f = 1.

B, Plots of Tj versus fx, the mole fraction of pentamers containing guest residues, are essentially linear to fx = 0.5. Extrapolation to the value of Tj at fx = 1 is used to provide an index of the relative hydrophobicities of the amino acid residues. This provides for a hydrophobicity scale which is based on the hydrophobic folding and assembly of interest. Adapted with permission from Urry, 1993a. 

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