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Motivation: Sampling the conformational space of biological macromolecules generates large sets of data with considerable complexity. Data-mining techniques, such as clustering, can extract meaningful information. Among them, the self-organizing maps (SOMs) algorithm has shown great promise; in particular since its computation time rises only linearly with the size of the data set. Whereas SOMs are generally used with few neurons, we investigate here their behavior with large numbers of neurons., Results: We present here a python library implementing the full SOM analysis workflow. Large SOMs can readily be applied on heavy data sets. Coupled with visualization tools they have very interesting properties. Descriptors for each conformation of a trajectory are calculated and mapped onto a 3D landscape, the U-matrix, reporting the distance between neighboring neurons. To delineate clusters, we developed the flooding algorithm, which hierarchically identifies local basins of the U-matrix from the global minimum to the maximum., Availability and Implementation: The python implementation of the SOM library is freely available on github: https://github.com/bougui505/SOM., Contact: michael.nilges@pasteur.fr or guillaume.bouvier@pasteur.fr, Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: The determination of protein structures satisfying distance constraints is an important problem in structural biology. Whereas the most common method currently employed is simulated annealing, there have been other methods previously proposed in the literature. Most of them, however, are designed to find one solution only., Results: In order to explore exhaustively the feasible conformational space, we propose here an interval Branch-and-Prune algorithm (iBP) to solve the Distance Geometry Problem (DGP) associated to protein structure determination. This algorithm is based on a discretization of the problem obtained by recursively constructing a search space having the structure of a tree, and by verifying whether the generated atomic positions are feasible or not by making use of pruning devices. The pruning devices used here are directly related to features of protein conformations., Conclusions: We described the new algorithm iBP to generate protein conformations satisfying distance constraints, that would potentially allows a systematic exploration of the conformational space. The algorithm iBP has been applied on three α-helical peptides.

Prion protein is a strongly conserved and ubiquitous glycoprotein. The conformational conversion of the non-pathogenic cellular prion isoform (PrP(C)) into a pathogenic scrapie isoform (PrP(Sc)) is a fundamental event in the onset of transmissible spongiform encephalopathies (TSE). During this conversion, helix H1 and its two flanking loops are known to undergo a conformational transition into a beta-like structure. In order to understand mechanisms which trigger this transconformation, sheep prion protein synthetic peptides spanning helix 1 and beta-strand 2 (residues 142-166) were studied: (1) the N3 peptide, studied earlier, is known to fold into beta-hairpin-like conformation in phosphate buffer at neutral pH and to adopt a helix H1 conformation when dissolved in trifluoroethanol/phosphate buffer mixture, (2) The R156A mutant (peptide R15) and (3) the Y155A mutant (peptide Y14) of the N3 peptide are studied by circular dichroism and NMR spectroscopy in this article. Structural characterization of these peptides highlights the key role of tyrosine 155 in the stabilization of the beta-hairpin-like conformation of the sheep peptide in phosphate buffer. We propose a model where tyrosine 155 could stabilize the beta-hairpin structure by creating a hydrophobic core in phosphate buffer, necessary to initiate the beta-type structure formation. In the turn, the side chain ionic interaction, E152-R156 described before, seems to play a minor role relative to the hydrophobic packing, as observed with the R156A mutation (peptide R15). Interestingly, homology at amino acid residue 155 could be responsible for the species barrier in TSE.