Residue solvent accessible surface areas

If this hypothesis is true, one could expect the solvent-accessible surface area (ASA) of the polypeptide backbone in the PPII conformation to be correlated with measured PPII helix-forming propensities. In order to test this, Monte Carlo computer simulations of short peptides Ac-Ala-Xaa-Ala-NMe (Xaa = Ala, Asn, Gin, Gly, lie, Leu, Met, Pro, Ser, Thr, and Val) were run. These particular residues were examined because their... 

The sum of the estimated average solvent-accessible surface areas, (ASA), for the peptide units (—CO—NH—) on either side of residue Xaa, plus the Ca of Xaa, in each peptide simulated are given in Table II. Also shown are the estimated PPII helix-forming propensities for each residue measured by Kelly et al. (2001) and A. L. Rucker, M. N. Campbell, and... 

Following the original work by Kauzmann on hydrophobic interactions and the determinations of the structures of myoglobin and hemoglobin, it was stated, and is still stated frequently (despite evidence to the contrary), that hydrophobic residues are buried in the interior of proteins and hydrophilic residues are exposed to solvent water. It was first shown by Klotz (1970 see also Lee and Richards, 1971) that a substantial proportion of the exposed solvent-accessible surface area of proteins is composed of nonpolar groups. This matter has been stressed in lectures for many years by one of the authors (H. McK.) (for a discussion of various approaches to this problem, see Edsall and McKenzie, 1983). In the case of lysozyme, a substantial proportion of the hydrophobic residues Leu, Val, He, Ala, Gly, Phe, Tyr, Trp, Met, and Pro are either fully exposed to solvent or at least have some atoms that are solvent accessible. Examples of hydrophobic residues that are surface exposed are Val-2, Phe-3, Leu-17, Phe-34, Leu-75, Trp-123, Pro-70, and Pro-79, with Trp-62, Trp-63, Ile-98, Trp-108, and Val-109 being on the surface of the cleft. Examples of the least-exposed ionizable side chains are Asp-66, Asp-52, Tyr-53, His-15, and Glu-35. 

The earlier strategy was used to evaluate the PF values associated with five histidine residues in the DHFR enzyme system when the enzyme was in its apo form and when the enzyme was conplexed with folate and NADP-t (see Table 10.2) [28]. The measured PF values ranged from 1.1 to 31.5. The three-dimensional structures of apo-DHFR and DHFR-folate-NADP-t complex have been solved by X-ray crystallography [31]. Therefore, it was possible to determine the solvent-accessible surface area at the... 

Residue Protection factor Solvent-accessible surface area (A ) ... 

The extent to which a model identifies the correct regions of the protein surfaces that interact may be assessed independently of the contacts between these regions. For this purpose, two parameters f IR and f OP are computed that represent respectively the fraction of interface residues in the target that is reproduced in the model and the fraction of interface residues in the model that does not match those in the target. Both are evaluated separately for each component of the complex. Interface residues are defined as those that lose accessible surface area when the two proteins associate, computed from the difference in solvent accessible surface area of the complex and the individual components taken in the bound form. 

However, just considering the individual properties of each amino acid type is not enough to determine its accessibility to the surrounding aqueous environment. There have been many attempts at developing analytical models with predictive value for determining buried or surface accessible amino acids in a folded polypeptide chain. These studies have concluded fractional assignments for each residue that relate to its accessible surface area (ASA) or its solvent exposed area (SEA). 

As well as predicting protein structure, it is also of interest to try to predict solvent accessibility from the protein s primary sequence of amino acid residues. Solvent accessibility concerns the area of a protein s surface that is exposed to the surrounding solvent. The importance of this concept is that these accessible regions have the potential to interact with other entities, including endogenous proteins and drugs. Similarly, if the protein of interest is an enzyme, only residues with solvent accessibility could be part of the enzyme s active site. This means that an interaction site of interest, one involved in signal transduction (see Krauss, 2003), requires spatial accessibility to the solvent (Ofiran and Rost, 2005). 

For an atom in the enzyme or the substrate to interact with the solvent it must be able to form Van der Waals contact with water molecules. The accessible surface area of an atom is defined as the area on the surface of a sphere, radius R on each point of which the centre of a solvent molecule can be placed in contact with the atom without penetrating any other atoms of the molecule (Fig. 12). R is the sum of the Van der Waals radii of the atom and solvent molecule [27]. There is a linear relationship between the solubility of hydrocarbons and the surface area of the cavity they form in water [28]. It has been estimated that the hydrophobicity of residues in proteins is 100 J/mole/A of accessible surface area [29]. The surface tension of water is 72 dynes/cm so to form a free surface area of water of 1 A costs 435 J/mole/A. The implication is that the free energy of cavity formation in water to receive the hydrophobic group is offset by favourable interactions (dispersion forces) between the solute and water. 

Figure 5 Residue solvent accessibility is usually measured by rolling a spherical water molecule over a protein surface and summing the area that can be accessed by this molecule on each residue (typical values range from 0 to 300 A-). To allow comparisons between the accessibility of long extended and spherical amino acids, typically relative values are compiled (actual area as percentage of maximally accessible area). A simplified descriptions distinguishes two states buried (here residues C and D) and exposed (here residues A, B, E, F, and G) residues. Since the packing density of native proteins resembles that of crystals, values for solvent accessibility provide upper and lower limits to the number of possible inter-residue contacts...

X-ray absorption spectroscopy has proved the presence of rhenium dioxide within this nanostructure [12]. Extraction of the surfactant with various solvents remained inefficient since either the surfactant persists within the composite or the nanostructure is lost. Calcination at mild temperatures as low as 300-350°C in nitrogen atmosphere leads to a mass loss under these pyrolytic conditions of about 50% with only little loss of the nanostructure. Similar results are obtained when the composite is oxidatively treated in an oxygen plasma for not more than ten minutes. Physisorption measurements on the calcined or plasma treated samples show only very small surface areas, which cannot be assigned to a mesoporous structure. Right now we believe that residual carbon may introduce some pore blocking effects within the nanostructure preventing good access of the inner pore surfaces. 

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