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Biomedical subjects

G D Rose

Publications and source records attributed to G D Rose.

At least 55 records · Page 3Linked to original sources
PubMed1988

Helix signals in proteins.

The alpha helix, first proposed by Pauling and co-workers, is a hallmark of protein structure, and much effort has been directed toward understanding which sequences can form helices. The helix hypothesis, introduced here, provides a tentative answer to this question. The hypothesis states that a necessary condition for helix formation is the presence of residues flanking the helix termini whose side chains can form hydrogen bonds with the initial four-helix greater than N-H groups and final four-helix greater than C-O groups; these eight groups would otherwise lack intrahelical partners. This simple hypothesis implies the existence of a stereochemical code in which certain sequences have the hydrogen-bonding capacity to function as helix boundaries and thereby enable the helix to form autonomously. The three-dimensional structure of a protein is a consequence of the genetic code, but the rules relating sequence to structure are still unknown. The ensuing analysis supports the idea that a stereochemical code for the alpha helix resides in its boundary residues.

Amino Acid Sequence↗
PubMed1987

The behavioral treatment of Raynaud's disease: a review.

Raynaud's disease is a peripheral vascular system disorder characterized by episodes of vasoconstriction in the hands and feet resulting in a lowering of skin temperature and pain. Recent studies are reviewed that focus on the behavioral treatment of Raynaud's disease--in particular, biofeedback and autogenic training. Methodological problems and other difficulties include the measurement of skin temperature, schedules of reinforcement/feedback, and characteristics of the experimenter and subject. Studies in this area indicate some promise for certain behavioral interventions, especially finger temperature biofeedback under cold stress conditions. On the other hand, further research is needed to clarify the mechanisms, especially that of vasodilation, and the applications of temperature biofeedback, as well as the role of attitudinal, interpersonal, and cognitive factors.

Autogenic Training↗
PubMed1986

Loops in globular proteins: a novel category of secondary structure.

The protein loop, a novel category of nonregular secondary structure, is a segment of contiguous polypeptide chain that traces a "loop-shaped" path in three-dimensional space; the main chain of an idealized loop resembles a Greek omega (omega). A systematic study was made of 67 proteins of known structure revealing 270 omega loops. Although such loops are typically regarded as "random coil," they are, in fact, highly compact substructures and may also be independent folding units. Loops are almost invariably situated at the protein surface where they are poised to assume important roles in molecular function and biological recognition. They are often observed to be modules of evolutionary exchange and are also natural candidates for bioengineering studies.

Protein Conformation↗
PubMed1986

Compact units in proteins.

An explicit measure of geometric compactness called the coefficient of compactness is introduced. This single value figure of merit identifies those continuous segments of the polypeptide chain having the smallest solvent-accessible surface area for their volume. These segments are the most compact units of the protein, and the larger ones correspond to conventional protein domains. To demonstrate the plausibility of this approach as a method of identifying protein domains, the measure is applied to lysozyme and ribonuclease to discover their constituent compact units. These units are then compared with domains, subdomains, and modules found by other methods. To show the sensitivity of the method, the measure is used to successfully differentiate between native and deliberately misfolded proteins [Novotný, J., Bruccoleri, R., & Karplus, M. (1984) J. Mol. Biol. 177, 787-818]. Methods that utilize only backbone atoms to define domains cannot distinguish between authentic and misfolded molecules because their backbone conformations are virtually superimposable. Compact units identified by this method exhibit a hierarchic organization. Such an organization suggests possible folding pathways that can be tested experimentally.

Hemerythrin↗
PubMed1986

Antigenic determinants in proteins coincide with surface regions accessible to large probes (antibody domains).

We evaluated surface areas on proteins that would be accessible to contacts with large (1-nm radius) spherical probes. Such spheres are comparable in size to antibody domains that contain antigen-combining sites. We found that all the reported antigenic sites correspond to segments particularly accessible to a large sphere. The antigenic sites were also evident as the most prominently exposed regions (hills and ridges) in contour maps of the solvent-accessible (small-probe) surface. In myoglobin and cytochrome c, virtually all of the van der Waals surface is accessible to the large probe and therefore potentially antigenic; in myohemerythrin, distinct large-probe-inaccessible, and nonantigenic, surface regions are apparent. The correlation between large-sphere-accessibility and antigenicity in myoglobin, lysozyme, and cytochrome c appears to be better than that reported to exist between antigenicity and segmental flexibility; that is, surface regions that are rigid often constitute antigenic epitopes, whereas some of the flexible parts of the molecules do not appear antigenic. We propose that the primary reason why certain polypeptide-chain segments are antigenic is their exceptional surface exposure, making them readily available for contacts with antigen-combining sites. Exposure of these segments frequently results in high mobility and, in consequence, to the reported correlation between antigenicity and segmental flexibility.

Cytochrome c Group↗
PubMed1985

Hydrophobicity of amino acid residues in globular proteins.

During biosynthesis, a globular protein folds into a tight particle with an interior core that is shielded from the surrounding solvent. The hydrophobic effect is thought to play a key role in mediating this process: nonpolar residues expelled from water engender a molecular interior where they can be buried. Paradoxically, results of earlier quantitative analyses have suggested that the tendency for nonpolar residues to be buried within proteins is weak. However, such analyses merely classify residues as either "exposed" or "buried." In the experiment reported in this article proteins of known structure were used to measure the average area that each residue buries upon folding. This characteristic quantity, the average area buried, is correlated with residue hydrophobicity.

Amino Acids↗
PubMed1983

Hierarchic organization of globular proteins. A control study.

In previous work, globular proteins of known structure were shown to be iteratively subdivisible into a hierarchy of disjunct, contiguous-chain regions, ranging in size from whole protein monomers down to individual helices and strands (1, 2). We now report the results of a similar analysis performed on a set of 1000 simulated chain folds that were generated by a method due to Schulz (3). The organization of these simulated proteins was found to be similar to that of authentic molecules. This control study strengthens earlier evidence suggesting that hierarchic architecture is a ubiquitous attribute of protein chain folds.

L-Lactate Dehydrogenase↗
PubMed1981

Folding units in globular proteins.

We present a method to identify all compact, contiguous-chain, structural units in a globular protein from x-ray coordinates. These units are then used to describe a complete set of hierarchic folding pathways for the molecule. Our analysis shows that the larger units are combinations of smaller units, giving rise to a structural hierarchy ranging from the whole protein monomer through supersecondary structures down to individual helices and strands. It turns out that there is more than one way to assemble the protein by self-association of its compact units. However, the number of possible pathways is small--small enough to be exhaustively explored by a computer program. The hierarchic organization of compact units in protein molecules is consistent with a model for folding by hierarchic condensation. In this model, neighboring hydrophobic chain sites interact to form folding clusters, with further stepwise cluster association giving rise to a population of folding intermediates.

Animals↗
PubMed1980

Hydrophobic basis of packing in globular proteins.

The self-assembly of globular proteins is often portrayed as a nucleation process in which the hydrogen bonding in segments of secondary structure is the precondition for further folding. We show here that this concept is unlikely because both the buried interior regions and the peptide chain turns of the folded protein (i.e., inside and outside) are predicted solely by the hydrophobicity of the residues, taken in sequential order along the chain. The helices and strands span the protein, and this observed secondary structure is seen to coincide with the regions predicted to be buried from hydrophobicity considerations alone. Our evidence suggests that linear chain regions rich in hydrophobic residues serve as small clusters that fold against each other, with concomitant or even later fixation of secondary structure. A helix or strand would arise in this folding process as one of a few energetically favorable alternatives for a given cluster, followed by a shift in the equilibrium between secondary structure conformers upon cluster association. the linera chain hydrophobicity alternates between locally maximal and minimal values, and these extrema partition the polypeptide chain into structural segments. This partitioning is seen in the x-ray structure as isodirectional segments bracketed between peptide chain-turns, with the segments expressed most often as helices and strands. the segment interactions define the geometry of the molecular interior and the chain-turns describe the predominant features of the molecular coastline. The segmentation of the molecule by linear chain hydrophobicity imposes a major geometric constraint upon possible folding events.

Amino Acids↗