Structure native

Both the structural and kinetic aspects of the protein-folding problem are complicated by the fact that folding takes place within a bath of water molecules. In fact, hydrophobic interactions are almost certainly crucial for both the relation of the sequence and the native structure, and the process by which a good sequence folds to its native structure. 

Simon I 1985 Investigation of protein refolding a special feature of native structure responsible for refolding ability J. Theor. Bioi. 113 703-10... 

We tested our new potential by applying a local optimization procedure to the potential of some proteins, starting with the native structure as given in the Brookhaven Protein Data Bank, and observing how far the coordinates moved through local optimization. For a good potential, one expects the optimizer to be close to the native structure. As in Ulrich et al. [34], we measure the distance between optimizer B and native structure A by the distance matrix error... 

Table 1. Distance matrix errors DME (in A) between optimizers and native structures...

M. H. Hao, M. R. Pincus, S. Rackovsky, and H. A. Scheraga. Unfolding and refolding of the native structure of bovine pancreatic trypsin inhibitor studied by computer simulations. Biochemistry, 32 9614-9631, 1993. 

The biologiccJ function of a protein or peptide is often intimately dependent upon the conformation(s) that the molecule can adopt. In contrast to most synthetic polymers where the individual molecules can adopt very different conformations, a protein usually exists in a single native state. These native states are found rmder conditions typically found in Uving cells (aqueous solvents near neutred pH at 20-40°C). Proteins can be unfolded (or denatured) using high-temperature, acidic or basic pH or certain non-aqueous solvents. However, this unfolding is often reversible cind so proteins can be folded back to their native structure in the laboratory. 

Example Crippen and Snow reported their success in developing a simplified potential for protein folding. In their model, single points represent amino acids. For the avian pancreatic polypeptide, the native structure is not at a potential minimum. However, a global search found that the most stable potential minimum had only a 1.8 Angstrom root-mean-square deviation from the native structure. 

A recent survey analyzed the accuracy of tliree different side chain prediction methods [134]. These methods were tested by predicting side chain conformations on nearnative protein backbones with <4 A RMSD to the native structures. The tliree methods included the packing of backbone-dependent rotamers [129], the self-consistent mean-field approach to positioning rotamers based on their van der Waals interactions [145],... 

This section briefly reviews prediction of the native structure of a protein from its sequence of amino acid residues alone. These methods can be contrasted to the threading methods for fold assignment [Section II.A] [39-47,147], which detect remote relationships between sequences and folds of known structure, and to comparative modeling methods discussed in this review, which build a complete all-atom 3D model based on a related known structure. The methods for ab initio prediction include those that focus on the broad physical principles of the folding process [148-152] and the methods that focus on predicting the actual native structures of specific proteins [44,153,154,240]. The former frequently rely on extremely simplified generic models of proteins, generally do not aim to predict native structures of specific proteins, and are not reviewed here. 

Glycine residues have more conformational freedom than any other amino acid, as discussed in Chapter 1. A glycine residue at a specific position in a protein has usually only one conformation in a folded structure but can have many different conformations in different unfolded structures of the same protein and thereby contribute to the diversity of unfolded conformations. Proline residues, on the other hand, have less conformational freedom in unfolded structures than any other residue since the proline side chain is fixed by an extra covalent bond to the main chain. Another way to decrease the number of possible unfolded structures of a protein, and hence stabilize the native structure, is, therefore, to mutate glycine residues to any other residue and to increase the number of proline residues. Such mutations can only be made at positions that neither change the conformation of the main chain in the folded structure nor introduce unfavorable, or cause the loss of favorable, contacts with neighboring side chains. 

Christian Anfmsen s experiments demonstrated that proteins can fold reversibly. A corollary result of Anfmsen s work is that the native structures of at least some globular proteins are thermodynamically stable states. But the matter of how a given protein achieves such a stable state is a complex one. Cyrus Levinthal pointed out in 1968 that so many conformations are possible for a typical protein that the protein does not have sufficient time to reach its most stable conformational state by sampling all the possible conformations. This argument, termed Levinthal s paradox, goes as follows consider a protein of 100 amino acids. Assume that there are only two conformational possibilities per amino acid, or = 1.27 X 10 ° possibilities. Allow 10 sec for... 

The target of vanadate-catalyzed photolysis is presumably an amino acid near the catalytic site of the Ca " -ATPase. The vanadate-catalyzed photocleavage at the V cleavage site in the absence of Ca " is 500 amino acids away from the C cleavage site which is attacked in the presence of Ca. Both sites are probably adjacent in the native structure to the catalytic site of the Ca -ATPase. 

Disruption of the native structure of a protein can also contribute to chemical instability by accelerating the rates of a variety of degradation routes, including deamidation, hydrolysis, oxidation, disulfide exchange, /1-elimination, and racemization. 

III PEG MPD Steric exclusion Repulsion from charges To hydrophobic regions Good precipitants stabilizers of native structure at low temp., unfolded structure at high temp. stabilizers and solubilizers of hydrophobic domains in proteins... 

The most obvious feature of the 15N-1H correlation spectrum of A131A is what is missing All of the peaks corresponding to the first 30 residues are absent. In the native structure these residues form a three-strand beta meander which combines with a two-... 

The ROA spectra of native and prehbrillar amyloidogenic human lysozyme are displayed in Figure 7, together with a MOLSCRIPT diagram of the native structure. The ROA spectrum of the native protein is very similar to that of hen lysozyme (Fig. 5). However, large changes have occurred in the ROA spectrum of the prehbrillar intermediate. In particular, the positive 1340 cm-1 ROA band assigned to hydrated... 

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