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Structure Propensities (structure + propensity)

Distribution by Scientific Domains
Chemistry100%

Kinds of Structure Propensities

  • secondary structure propensity
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    Selected Abstracts

    Time-averaged predictions of folded and misfolded peptides using a reduced physicochemical model

    JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 7 2008
    Oliver J. Clarke
    Abstract Energy-based methods for calculating time-averaged peptide structures are important for rational peptide design, for defining local structure propensities in large protein chains, and for exploring the sequence determinants of amyloid formation. High-end methods are currently too slow to be practicable, and will remain so for the foreseeable future. The challenge is to create a method that runs quickly on limited computer resources and emulates reality sufficiently well. We have developed a simplified off-lattice protein model, incorporating semi-empirical physicochemical potentials, and combined it with an efficient Monte Carlo method for calculating time-averaged peptide structures. Reasonably accurate predictions are found for a set of small ,-helical and ,-hairpin peptides, and we demonstrate a potential application in measuring local structure propensities in protein chains. Time-averaged structures have also been calculated for a set of small peptides known to form ,-amyloid fibrils. The simulations were of three interacting peptides, and in each case the time-averaged structure describes a three-stranded ,-sheet. The performance of our method in measuring the propensities of small peptides to self-associate into possible prefibrillar species compares favorably with more detailed and CPU-intensive approaches. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008 [source]

    15N relaxation study of the amyloid ,-peptide: structural propensities and persistence length

    MAGNETIC RESONANCE IN CHEMISTRY, Issue S1 2006
    Jens Danielsson
    Abstract The dynamics of monomeric Alzheimer A,(1,40) in aqueous solution was studied using heteronuclear NMR experiments. 15N NMR relaxation rates of amide groups report on the dynamics in the peptide chain and make it possible to estimate structural propensities from temperature-dependent relaxation data and chemical shifts change analysis. The persistence length of the polypeptide chain was determined using a model in which the influence of neighboring residue relaxation is assumed to decay exponentially as a function of distance. The persistence length of the A,(1,40) monomer was found to decrease from eight to three residues when temperature was increased from 3 to 18 °C. At 3 °C the peptide shows structural propensities that correlate well with the suggested secondary structure regions of the peptide to be present in the fibrils, and with the ,-helical structure in membrane-mimicking systems. Our data leads to a structural model for the monomeric soluble ,-peptide with six different regions of secondary structure propensities. The peptide has two regions with ,-strand propensity (residues 16,24 and 31,40), two regions with high PII-helix propensity (residues 1,4 and 11,15) and two unstructured regions with higher mobility (residues 5,10 and 25,30) connecting the structural elements. Copyright © 2006 John Wiley & Sons, Ltd. [source]

    Sensitivity of secondary structure propensities to sequence differences between ,- and ,-synuclein: Implications for fibrillation

    PROTEIN SCIENCE, Issue 12 2006
    Joseph A. Marsh
    Abstract The synucleins are a family of intrinsically disordered proteins involved in various human diseases. ,-Synuclein has been extensively characterized due to its role in Parkinson's disease where it forms intracellular aggregates, while ,-synuclein is overexpressed in a majority of late-stage breast cancers. Despite fairly strong sequence similarity between the amyloid-forming regions of ,- and ,-synuclein, ,-synuclein has only a weak propensity to form amyloid fibrils. We hypothesize that the different fibrillation tendencies of ,- and ,-synuclein may be related to differences in structural propensities. Here we have measured chemical shifts for ,-synuclein and compared them to previously published shifts for ,-synuclein. In order to facilitate direct comparison, we have implemented a simple new technique for re-referencing chemical shifts that we have found to be highly effective for both disordered and folded proteins. In addition, we have developed a new method that combines different chemical shifts into a single residue-specific secondary structure propensity (SSP) score. We observe significant differences between ,- and ,-synuclein secondary structure propensities. Most interestingly, ,-synuclein has an increased ,-helical propensity in the amyloid-forming region that is critical for ,-synuclein fibrillation, suggesting that increased structural stability in this region may protect against ,-synuclein aggregation. This comparison of residue-specific secondary structure propensities between intrinsically disordered homologs highlights the sensitivity of transient structure to sequence changes, which we suggest may have been exploited as an evolutionary mechanism for fast modulation of protein structure and, hence, function. [source]