Hydrophobicity, prediction

Torres, E. Tinoco, R., and VazquezDuhalt, R., Solvent Hydrophobicity Predicts Biocatalytic Behaviour of Lignin Peroxidase and Cytochrome C in Aqueous Solution of Water-Miscible Organic Solvents. Journal of Biotechnology, 1996. 49(1-3) pp. 59-67. 

The predicted amino acid sequence of the clone obtained from NG108-15 cells (Fig. 1) identified the delta opioid receptor as a member of the seven-transmembrane family of G protein-coupled receptors. The receptor had seven hydrophobic, predicted transmembrane domains (TMDs) and close homology to many other G protein-coupled receptors, including receptors for somatostatin, interleukin-8 and angiotensin. This structural homology confirmed the widely held notion that opioid receptors would indeed be members of this enormous family of receptors (the human genome has recently been calculated to contain approximately 950 G protein-coupled receptors [29]). 

Given descriptions of two compounds that differ in the percentages of their structures that are polar and nonpolar (hydrophilic and hydrophobic), predict their relative solubilities in water and in hexane. 

K, V N Viswanadhan and J J Wendoloski 1998. Prediction of Hydrophobic (Lipophilic) lerties of Small Organic Molecules Using Fragmental Methods An Analysis of ALOGP and GP Methods. Journal of Physical Chemistry 102 3762-3772. 

If one would ask a chemist not burdened with any knowledge about the peculiar thermodynamics that characterise hydrophobic hydration, what would happen upon transfer of a nonpolar molecule from the gas phase to water, he or she would probably predict that this process is entropy driven and enthalpically highly unfavourable. This opinion, he or she wo ild support with the suggestion that in order to create room for the nonpolar solute in the aqueous solution, hydrogen bonds between water molecules would have to be sacrificed. 

The Smith-Ewart expression (eq. 1) accurately predicts the particle number for hydrophobic monomers like styrene and butadiene (21), but fails to predict the particle number (22) for more hydrophilic monomers like methyl methacrylate and vinyl acetate. A new theory based on homogeneous particle... 

Simplified models for proteins are being used to predict their stmcture and the folding process. One is the lattice model where proteins are represented as self-avoiding flexible chains on lattices, and the lattice sites are occupied by the different residues (29). When only hydrophobic interactions are considered and the residues are either hydrophobic or hydrophilic, simulations have shown that, as in proteins, the stmctures with optimum energy are compact and few in number. An additional component, hydrogen bonding, has to be invoked to obtain stmctures similar to the secondary stmctures observed in nature (30). 

Strkcttire inflkence. The specificity of interphase transfer in the micellar-extraction systems is the independent and cooperative influence of the substrate molecular structure - the first-order molecular connectivity indexes) and hydrophobicity (log P - the distribution coefficient value in the water-octanole system) on its distribution between the water and the surfactant-rich phases. The possibility of substrates distribution and their D-values prediction in the cloud point extraction systems using regressions, which consider the log P and values was shown. Here the specificity of the micellar extraction is determined by the appearance of the host-guest phenomenon at molecular level and the high level of stmctural organization of the micellar phase itself. 

On the basis of data obtained the possibility of substrates distribution and their D-values prediction using the regressions which consider the hydrophobicity and stmcture of amines was investigated. The hydrophobicity of amines was estimated by the distribution coefficient value in the water-octanole system (Ig P). The molecular structure of aromatic amines was characterized by the first-order molecular connectivity indexes ( x)- H was shown the independent and cooperative influence of the Ig P and parameters of amines on their distribution. Evidently, this fact demonstrates the host-guest phenomenon which is inherent to the organized media. The obtained in the research data were used for optimization of the conditions of micellar-extraction preconcentrating of metal ions with amines into the NS-rich phase with the following determination by atomic-absorption method. 

The comparison of predicting capabilities of two kinds of hydrophobicity evaluations is of interest. For these purpose partition coefficients P and P for a number of benzodiazepines gidazepam (I), medazepam (II), nitrazepam (III), oxazepam (IV), lorazepam (V) and diazepam (VI) were determined. 

WA Lim, A Hodel, RT Sauer, FM Richards. The crystal structure of a mutant protein with altered but improved hydrophobic core packing. Proc Natl Acad Sci USA 91 423-427, 1994. PB Harbury, B Tidor, PS Kim. Repacking proteins cores with backbone freedom Structure prediction for coiled coils. Pi oc Natl Acad Sci USA 92 8408-8412, 1995. 

The most common location for an a helix in a protein structure is along the outside of the protein, with one side of the helix facing the solution and the other side facing the hydrophobic interior of the protein. Therefore, with 3.6 residues per turn, there is a tendency for side chains to change from hydrophobic to hydrophilic with a periodicity of three to four residues. Although this trend can sometimes be seen in the amino acid sequence, it is not strong enough for reliable stmctural prediction by itself, because residues that face the solution can be hydrophobic and, furthermore, a helices can be either completely buried within the protein or completely exposed. Table 2.1 shows examples of the amino acid sequences of a totally buried, a partially buried, and a completely exposed a helix. 

Alpha helices that cross membranes are in a hydrophobic environment. Therefore, most of their side chains are hydrophobic. Long regions of hydrophobic residues in the amino acid sequence of a protein that is membrane-bound can therefore be predicted with a high degree of confidence to be transmembrane helices, as will be discussed in Chapter 12. 

Rose, G.D. Prediction of chain turns in globular proteins on a hydrophobic basis. Nature 272 586-590, 1978. 

Since the outside of the barrel faces hydrophobic lipids of the membrane and the inside forms the solvent-exposed channel, one would expect the P strands to contain alternating hydrophobic and hydrophilic side chains. This requirement is not strict, however, because internal residues can be hydrophobic if they are in contact with hydrophobic residues from loop regions. The prediction of transmembrane p strands from amino acid sequences is therefore more difficult and less reliable than the prediction of transmembrane a helices. 

In contrast, the transmembrane helices observed in the reaction center are embedded in a hydrophobic surrounding and are built up from continuous regions of predominantly hydrophobic amino acids. To span the lipid bilayer, a minimum of about 20 amino acids are required. In the photosynthetic reaction center these a helices each comprise about 25 to 30 residues, some of which extend outside the hydrophobic part of the membrane. From the amino acid sequences of the polypeptide chains, the regions that comprise the transmembrane helices can be predicted with reasonable confidence. 

The most important general lesson is that there are hydrophobic transmembrane helices, the positions of which within the amino acid sequence can be predicted with reasonable accuracy. This applies both to the single transmembrane-spanning helix within the H polypeptide chain of the reaction center and the five transmembrane helices of the L and M chains that... 

Over 20 different methods have been proposed for predictions of secondary stmcture they can be categorized in two broad classes. The empirical statistical methods use parameters obtained from analyses of known sequences and tertiary stmctures. All such methods are based on the assumption that the local sequence in a short region of the polypeptide chain determines local stmcture as we have seen, this is not a universally valid assumption. The second group of methods is based on stereochemical criteria, such as compactness of form with a tightly packed hydrophobic core and a polar surface. Three frequently used methods are the empirical approaches of P.Y. Chou and G.D. Fasman and of J. Gamier, D.J. Osguthorpe and B. Robson (the GOR method), and third, the stereochemical method of V.l. him. 

For each fold one searches for the best alignment of the target sequence that would be compatible with the fold the core should comprise hydrophobic residues and polar residues should be on the outside, predicted helical and strand regions should be aligned to corresponding secondary structure elements in the fold, and so on. In order to match a sequence alignment to a fold, Eisenberg developed a rapid method called the 3D profile method. The environment of each residue position in the known 3D structure is characterized on the basis of three properties (1) the area of the side chain that is buried by other protein atoms, (2) the fraction of side chain area that is covered by polar atoms, and (3) the secondary stmcture, which is classified in three states helix, sheet, and coil. The residue positions are rather arbitrarily divided into six classes by properties 1 and 2, which in combination with property 3 yields 18 environmental classes. This classification of environments enables a protein structure to be coded by a sequence in an 18-letter alphabet, in which each letter represents the environmental class of a residue position. 

During this process of designing sequence changes, models were built and assessed to ensure that there were no obvious steric clashes and that the hydrophobic core was well packed. Furthermore, secondary structure prediction was also used to monitor the progress of change and to choose among different possible substitutions. The final sequence (see Table 17.3) contains 28 changes it had 50% identity to B1 and the similarity to Rop had increased from 5.4% identity to 41%. 

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