Solvent-exposed residues

The Liskamp group also examined the ability of peptoid-peptide hybrids to be bound by the MHC Class II receptor, an important component of the human immune system [39]. Two of three peptoid substitutions in the 14-residue peptide caused substantial decreases in binding affinity, despite the fact that these were solvent-exposed residues. These results were attributed to a loss of hydrogen-bond contacts as well as to steric clashes caused by unfavorable positioning of the new side chain groups. 

Amino acid substitutions on the native y52 8sKIpeptide, coiled-coil domain of human fibrin were able to stabilize the coiled-coil formation. These substitutions were targeted to the positions that compose the interface between coiled-coil strands while the solvent-exposed residues were left unperturbed. This strategy aimed at reducing the likelihood of immunogenicity for future in vivo apphcafion of these materials. In contrast to PEG block copolymers with end blocks that are not used for directed assembly, PEG copolymers with coiled-coil protein motives aim to enhance intermolecular interactions and control over the assembly conditions [85, 173]. 

The authors expressed PKA consisting of 353 amino acids, of which eight are prolines. Resonances of 274 backbone amide peaks were visible in the spectrum, of which 191 were assigned. It was possible to assign resonances for the N- and C-terminal sequences, the majority of the N-lobe, including the glycine-rich loop, and most of the solvent-exposed residues of the C-lobe. This enabled a determination of the structure for the more flexible parts of the structure. However, many correlations were missing for the... 

Mapping of the tumor-derived VHL mutations on the VHL structure revealed two patches of solvent-exposed residues (Figure 7.6). One patch is located on the portion of the a-domain involved in ElonginC binding, confirming the role ElonginC binding plays in the tumor suppressor function of VHL. The second patch. 

The final session demonstrates how to characterize a protein region as random-izable. For a set of solvent-exposed residues of an immunoglobulin structure, 103 mutants are randomly generated. We examine how many of these mutants are destabilized with respect to the wild type. The analysis is repeated with an alternative set of residues that correspond to part of the natural epitope of the immunoglobulin structure. 

CGTase nitration induces an 11.5 nm shift in the fluorescence maximum to shorter wavelengths (A.max = 326.5 nm instead of 338 nm for 8 mM TNM), suggesting a relative increase in the buried tryptophan fluorescence. Tyr -> Trp energy transfer may then involve solvent-exposed residue(s). 

Our QM/MM model—the discrete (or direct) reaction field (DRF) model—treats the various terms in Eq. (3-1) separately and on the basis of their own intrinsic physical meaning [3,10,31,32,38,59,74], Historically, DRF was developed to study biochemical problems, in particular for unraveling the reaction mechanism of papain. For that we went stepwise from a model active site [75] to a model active site plus a point charge representation of an a-helix [76,77,78], then to a model with a polarizable helix [78,79], and finally to an all-atom treatment of the enzyme [41]. Furthermore, we extended these studies with an exercise—with the continuum version—to show that a solvent-exposed residue has no effect on the reaction mechanism [80], Up to then we considered the protein as a peculiar solvent the real solvents, requiring extensive MC or MD simulations, came later. 

Extensive structure function studies have identified Phe , which is centrally disposed on the gplSO CHR interface as critical for ligand engagement for all human gp 130-cytokines (Fig. 5) (Bravo et al, 1998 Horsten et al, 1997 Kurth et al, 1999 Li and Nicholas, 2002). The use of a bulky hydrophobic solvent exposed residue at site 11 is also observed in the GH/GHR complex (de Vos et al, 1992) and the EPO/EPOR complex (Syed et al, 1998) suggesting a more fundamental role in mediating protein-protein interactions. In these cases, a bulky tyrosine docks into a hydrophobic pocket on the cytokine formed by the Ca backbone of helix C. 

When the Trp residue is located in a hydrophobic environment of the protein its <1>f is enhanced and importantly the fluorescence spectral maximum is shifted to a much higher energy than that normally seen for a solvent exposed residue. 

The emission maximum of tryptophan in proteins can range fiom 308 mn for a residue buried in a completely apolar enviroiunent (as in the single tryptophan variant of azurin (37)) to 350 nm for a fully solvent-exposed residue (38-40). Due to their apolar character, tryptophan residues are usually either fully or partially buried in the three-dimensional structures of proteins and are expected to have emission maxima from 320 to 340 nm. Unfolding of a protein, and concomitant increase in the solvent exposure of tiyptophan residues will invariably lead to a red-shift in the fluorescence of a tryptophan-containing protein. 

Another modification in modeling the dielectric was described recently by Demchuk and Wade." They divided ionizable protein groups into two classes solvent-exposed residues for which the best results are obtained if the protein dielectric constant is set close to that of the aqueous solvent, and buried residues for which the best results are obtained using lower, site-specific protein dielectric constants. These two classes of ionizable sites can be distinguished using a criterion based on desolvation energy. 

A group was considered in contact with the external solvent when it had a protonatable atom that bordered the external solvent-accessible surface. Our convention is to call the solvent exposed residue the start of the proton transfer pathway and the carbonyl oxygen on the quinone the end of the pathway. 

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