Proteins conformational behavior

An extensive series of review papers and research papers has been published by Tanford on protein denaturation. The stability of protein structure has been discussed in several articles by Privalov, with particular attention paid to the small globular proteins. Conformational behavior is dependent on the inter- and intramolecular forces experienced by these macromolecules. Weakly polar interactions in proteins play an important role and have been discussed by Burley and Petsko. Gurd and Rothgeb have described the motions observed in these nonquiescent macromolecules. Studies of the calorimetrically determined dynamics of complex unfolding transitions in proteins have been reviewed by Freire et al ... 

Farmer RS, Kiick KL (2005) Conformational behavior of chemically reactive alanine-rich repetitive protein polymers. Biomacromolecules 6 1531-1539... 

Because simple lattice models take no account of local directional preferences, they fail to model these important local restraints on protein structure. Instead, they rely almost entirely on long-range interactions to encode the most stable conformation(s) (Dill et al., 1995). Thus the ability of lattice models to reproduce protein-like behavior must be called into question. And though their simplicity makes them intellectually attractive, their use in teaching and modeling protein-like behavior must be qualified with a caveat that local directional preferences have been ignored. 

Cyclic peptides have been synthesized not only for the purpose of improving biological activities and selectivity, but also to explore basic features of secondary structures in peptides and to investigate with such mimetic compounds the conformational behavior of proteins. For this purpose artificial building blocks have been frequently used or amide bonds have been modified isosterically. Nature also offers a variety of modifications in cyclic peptides that are critically involved in their bioactivity. Some of the most common natural and synthetic modifications including unusual structural elements such as thiazoles (and dihy-drothiazoles) and oxazoles (and dihydrooxazoles) with broad synthetic applications will be presented in the following section. 

The main conclusion drawn from the simulations [170] is that in the presence of monovalent counterions, the charged protein-like copolymers can be soluble, even in a very poor solvent for hydrophobic units. There are three temperature regimes, which are characterized by different spatial organization of polyions and their conformational behavior. 

Morgan, F., Leonil, J., Molle, D., and Bouhallab, S. 1999a. Modification of bovine (3-lactoglobulin by glycation in a powdered state or in an aqueous solution effect on association behavior and protein conformation. J. Agric. Food Chem. 47, 83-91. 

All of these effects impact on the loading capacity of a particular HPLC sorbent, which can thus exhibit subtly different selectivity-capacity dependencies with different classes of polypeptides and proteins. Such behavior has been documented8,78,160,150,227-230 for enzymes and other proteins in a variety of studies. For example, when conformational reordering of a protein structure occurs in both the mobile phase and the stationary phase, this will... 

Rotation about heteroatom-heteroatom single bonds has been investigated for such cases as 0-0 (peroxides) and N-N (hydrazines) systems. Of greater relevance to biochemistry is the disulfide bond since its geometry is one of the determining factors in protein structure. The conformational behavior of a number of dialkyl disulfides (LXXVII) has been studied ([89], and refs, therein) showing the preferred... 

Several thermodynamic and kinetic behaviors of enzyme-catalyzed reactions performed in ILs, with respect to enzymatic reactions carried out in conventional solvents, could lead to an improvement in the process performance [34—37]. ILs showed an over-stabilization effect on biocatalysts [38] on the basis of the double role played by these neoteric solvents ILs could provide an adequate microenvironment for the catalytic action of the enzyme (mass transfer phenomena and active catalytic conformation) and if they act as a solvent, ILs may be regarded as liquid immobilization supports, since multipoint enzyme-1L interactions (hydrogen. Van der Waals, ionic, etc.) may occur, resulting in a flexible supramolecular not able to maintain the active protein conformation [39]. Their polar and non-coordinating properties hold considerable potential for enantioselective reactions since profound effects on reactivities and selectivities are expected [40]. In recent years attention has been focused on the appUcation of ILs as reaction media for enantioselective processes [41—43]. 

A solvent which has been foimd to be of great interest in connection with protein conformation studies is ethylene glycol. Sage and Singer (1958, 1962) have investigated in some detail the properties of RNase in pure ethylene glycol, containing added neutral electrolyte. They examined the ultraviolet absorption spectrum, the ionization behavior of the tyrosine residues by spectrophotometric titration experiments, and the optical rotatory dispersion of the system. 

Figure 24.2a shows dual fluorescence intensity trajectories simultaneously recorded from a donor-acceptor labeled T4 lysozyme in the presence of substrate at pH 7.2. The anticorrelated fluctuations (Fig. 24.2a and b) are due to spFRET, reporting the donor-acceptor distance change associated with the protein conformational motion. Likewise, fluorescence trajectories of donor-acceptor labeled T4 lysozyme without substrates did not show anticorrelated behavior (Fig. 24.2c and d). We attribute this conformational motion to an enzymatic-related motion, most likely the open-closed hinge-bending motion... 

The specific correlations of functional groups with the chemical shifts of carbon and associated protons are always important tools for structure elucidation of simple sugars as well as complex oligosaccharides. The conformational behavior [65,66] of a particular disaccharide and oligosaccharide in solution is determined not only by intramolecular interactions but also by potential interactions that exist between the oligosaccharide and its environment. In particular, the nature of the solvent or more generally the environment in which the compound finds itself, can profoundly affect its geometry. Two such important factors, namely the fully solvated state (i. e. the molecule free in solution) and the molecule solvated by a macromolecular receptor (i. e. the molecule bound to the active site of the protein) contribute to the preferred conformation. 

The importance of cation binding to modulate the conformational behavior and molecular recognition features of different oligosaccharides, particularly of the aminoglycoside antibiotic family, has also been addressed,250 together with the concomitant implications for the geometric and thermodynamic features of the interaction processes with nucleic acid and protein receptors 251... 

It is possible to create simplified models that avoid atomic detail and instead rely on a more schematic residue-based view. A great deal is known from polymer theory about the behavior of these simplified models. Models can be constructed with a minimal amount of information and tested to see if they exhibit the behavior of actual proteins. If they do, then fundamental questions can be raised about protein stability. These include the relative importance of various constraints and intramolecular interactions. In this way, qualitative insights into protein conformation and folding can be gained. Because these models are simplified, many of the terms in the potential function do not correspond directly to actual energies, but instead are parameterized empirically to produce observed properties of interest. Skolnick and Kolinski have recently reviewed these topics. ... 

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