This is an RSS newsfeed from BioMed Central It is intended to be used with an RSS reader. For more information about RSS newsfeeds from BioMed Central, visit http://www.biomedcentral.com/info/about/rss/ http://www.biomedcentral.com/bmcstructbiol/mostviewed/ Most viewed articles in last 30 days from BMC Structural Biology (ISSN 1472-6807) published by BioMed Central Background: PSAIA (Protein Structure and Interaction Analyzer) was developed to compute geometric parameters for large sets of protein structures in order to predict and investigate protein-protein interaction sites. Results: In addition to most relevant established algorithms, PSAIA offers a new method PIADA (Protein Interaction Atom Distance Algorithm) for the determination of residue interaction pairs. We found that PIADA produced more satisfactory results than comparable algorithms implemented in PSAIA.Particular advantages of PSAIA include its capacity to combine different methods to detect the locations and types of interactions between residues and its ability, without any further automation steps, to handle large numbers of protein structures and complexes. Generally, the integration of a variety of methods enables PSAIA to offer easier automation of analysis and greater reliability of results.PSAIA can be used either via a graphical user interface or from the command-line. Results are generated in either tabular or XML format. Conclusion: In a straightforward fashion and for large sets of protein structures, PSAIA enables the calculation of protein geometric parameters and the determination of location and type for protein-protein interaction sites. XML formatted output enables easy conversion of results to various formats suitable for statistic analysis.Results from smaller data sets demonstrated the influence of geometry on protein interaction sites. Comprehensive analysis of properties of large data sets lead to new information useful in the prediction of protein-protein interaction sites. http://www.biomedcentral.com/1472-6807/8/21 Josip Mihel, Mile Šikić, Sanja Tomić, Branko Jeren and Kristian Vlahoviček BMC Structural Biology 2008, 8:21 Number of accesses: 691 2008-04-09 doi:10.1186/1472-6807-8-21 BMC Structural Biology 1472-6807 8 21 2008-04-09 Background: Several different methods for contact prediction succeeded within the Sixth Critical Assessment of Techniques for Protein Structure Prediction (CASP6). The most relevant were non-local contact predictions for targets from the most difficult categories: fold recognition-analogy and new fold. Such contacts could provide valuable structural information in case a template structure cannot be found in the PDB. Results: We described comprehensive tests of the effectiveness of contact data in various aspects of de novo modeling with CABS, an algorithm which was used successfully in CASP6 by the Kolinski-Bujnicki group. We used the predicted contacts in a simple scoring function for the post-simulation ranking of protein models and as a soft bias in the folding simulations and in the fold-refinement procedure. The latter approach turned out to be the most successful. The CABS force field used in the Replica Exchange Monte Carlo simulations cooperated with the true contacts and discriminated the false ones, which resulted in an improvement of the majority of Kolinski-Bujnicki's protein models. In the modeling we tested different sets of predicted contact data submitted to the CASP6 server. According to our results, the best performing were the contacts with the accuracy balanced with the coverage, obtained either from the best two predictors only or by a consensus from as many predictors as possible. Conclusion: Our tests have shown that theoretically predicted contacts can be very beneficial for protein structure prediction. Depending on the protein modeling method, a contact data set applied should be prepared with differently balanced coverage and accuracy of predicted contacts. Namely, high coverage of contact data is important for the model ranking and high accuracy for the folding simulations. http://www.biomedcentral.com/1472-6807/8/36 Dorota Latek and Andrzej Kolinski BMC Structural Biology 2008, 8:36 Number of accesses: 425 2008-08-11 doi:10.1186/1472-6807-8-36 BMC Structural Biology 1472-6807 8 36 2008-08-11 Background: Many studies have examined rules governing two aspects of protein structures: short segments and proteins' structural domains. Nevertheless, the organization and nature of the conformational space of segments with intermediate length between short segments and domains remain unclear. Conformational spaces of intermediate length segments probably differ from those of short segments. We investigated the identification and characterization of the boundary(s) between peptide-like (short segment) and protein-like (long segment) distributions. We generated ensembles embedded in globular proteins comprising segments 10–50 residues long. We explored the relationships between the conformational distribution of segments and their lengths, and also protein structural classes using principal component analysis based on the intra-segment Cα-Cα atomic distances. Results: Our statistical analyses of segment conformations and length revealed critical dual transitions in their conformational distribution with segments derived from all four structural classes. Dual transitions were identified with the intermediate phase between the short segments and domains. Consequently, protein segment universes were categorized. i) Short segments (10–22 residues) showed a distribution with a high frequency of secondary structure clusters. ii) Medium segments (23–26 residues) showed a distribution corresponding to an intermediate state of transitions. iii) Long segments (27–50 residues) showed a distribution converging on one huge cluster containing compact conformations with a smaller radius of gyration. This distribution reflects the protein structures' organization and protein domains' origin. Three major conformational components (radius of gyration, structural symmetry with respect to the N-terminal and C-terminal halves, and single-turn/two-turn structure) well define most of the segment universes. Furthermore, we identified several conformational components that were unique to each structural class. Those characteristics suggest that protein segment conformation is described by compositions of the three common structural variables with large contributions and specific structural variables with small contributions. Conclusion: The present results of the analyses of four protein structural classes show the universal role of three major components as segment conformational descriptors. The obtained perspectives of distribution changes related to the segment lengths using the three key components suggest both the adequacy and the possibility of further progress on the prediction strategies used in the recent de novo structure-prediction methods. http://www.biomedcentral.com/1472-6807/8/37 Kazuyoshi Ikeda, Takatsugu Hirokawa, Junichi Higo and Kentaro Tomii BMC Structural Biology 2008, 8:37 Number of accesses: 351 2008-08-13 doi:10.1186/1472-6807-8-37 BMC Structural Biology 1472-6807 8 37 2008-08-13 Background: There are considerable differences between bacterial and mammalian glycans. In contrast to most eukaryotic carbohydrates, bacterial glycans are often composed of repeating units with diverse functions ranging from structural reinforcement to adhesion, colonization and camouflage. Since bacterial glycans are typically displayed at the cell surface, they can interact with the environment and, therefore, have significant biomedical importance. Results: The sequence characteristics of glycans (monosaccharide composition, modifications, and linkage patterns) for the higher bacterial taxonomic classes have been examined and compared with the data for mammals, with both similarities and unique features becoming evident. Compared to mammalian glycans, the bacterial glycans deposited in the current databases have a more than ten-fold greater diversity at the monosaccharide level, and the disaccharide pattern space is approximately nine times larger. Specific bacterial subclasses exhibit characteristic glycans which can be distinguished on the basis of distinctive structural features or sequence properties. Conclusions: For the first time a systematic database analysis of the bacterial glycome has been performed. This study summarizes the current knowledge of bacterial glycan architecture and diversity and reveals putative targets for the rational design and development of therapeutic intervention strategies by comparing bacterial and mammalian glycans. http://www.biomedcentral.com/1472-6807/8/35 Stephan Herget, Philip V Toukach, Rene Ranzinger, William E Hull, Yuriy A Knirel and Claus-Wilhelm von der Lieth BMC Structural Biology 2008, 8:35 Number of accesses: 318 2008-08-11 doi:10.1186/1472-6807-8-35 BMC Structural Biology 1472-6807 8 35 2008-08-11 Background: Recently, we reported a unique approach to preserve the activity of some proteins in the presence of the denaturing agent, Sodium Dodecyl Sulfate (SDS). This was made possible by addition of the amphipathic solvent 2,4-Methyl-2-PentaneDiol (MPD), used as protecting but also as refolding agent for these proteins. Although the persistence of the protein activity in the SDS/MPD mixture was clearly established, preservation of their structure was only speculative until now. Results: In this paper, a detailed X-ray study addresses the pending question. Crystals of hen egg-white lysozyme were grown for the first time in the presence of MPD and denaturing concentrations of SDS. Depending on crystallization conditions, tetragonal crystals in complex with either SDS or MPD were collected. The conformation of both structures was very similar to the native lysozyme and the obtained complexes of SDS-lysozyme and MPD-lysozyme give some insights in the interplay of protein-SDS and protein-MPD interactions. Conclusion: This study clearly established the preservation of the enzyme structure in a SDS/MPD mixture. It is hypothesized that high concentrations of MPD would change the properties of SDS and lower or avoid interactions between the denaturant and the protein. These structural data therefore support the hypothesis that MPD avoids disruption of the enzyme structure by SDS and can protect proteins from SDS denaturation. http://www.biomedcentral.com/1472-6807/8/29 Catherine Michaux, Jenny Pouyez, Johan Wouters and Gilbert G Privé BMC Structural Biology 2008, 8:29 Number of accesses: 294 2008-06-03 doi:10.1186/1472-6807-8-29 BMC Structural Biology 1472-6807 8 29 2008-06-03 Background: Automatic protein modelling pipelines are becoming ever more accurate; this has come hand in hand with an increasingly complicated interplay between all components involved. Nevertheless, there are still potential improvements to be made in template selection, refinement and protein model selection. Results: In the context of an automatic modelling pipeline, we analysed each step separately, revealing several non-intuitive trends and explored a new strategy for protein conformation sampling using Genetic Algorithms (GA). We apply the concept of alternating evolutionary pressure (AEP), i.e. intermediate rounds within the GA runs where unrestrained, linear growth of the model populations is allowed. Conclusion: This approach improves the overall performance of the GA by allowing models to overcome local energy barriers. AEP enabled the selection of the best models in 40% of all targets; compared to 25% for a normal GA. http://www.biomedcentral.com/1472-6807/8/34 Marc N Offman, Alexander L Tournier and Paul A Bates BMC Structural Biology 2008, 8:34 Number of accesses: 284 2008-08-01 doi:10.1186/1472-6807-8-34 BMC Structural Biology 1472-6807 8 34 2008-08-01 Background: The Ramachandran plot is a fundamental tool in the analysis of protein structures. Of the 4 basic types of Ramachandran plots, the interactions that determine the generic and proline Ramachandran plots are well understood. The interactions of the glycine and pre-proline Ramachandran plots are not. Results: In glycine, the ψ angle is typically clustered at ψ = 180° and ψ = 0°. We show that these clusters correspond to conformations where either the Ni+1 or O atom is sandwiched between the two Hα atoms of glycine. We show that the shape of the 5 distinct regions of density (the α, αL, βS, βP and βPR regions) can be reproduced with electrostatic dipole-dipole interactions. In pre-proline, we analyse the origin of the ζ region of the Ramachandran plot, a region unique to pre-proline. We show that it is stabilized by a COi-1···CδHδi+1 weak hydrogen bond. This is analogous to the COi-1···NHi+1 hydrogen bond that stabilizes the γ region in the generic Ramachandran plot. Conclusion: We have identified the specific interactions that affect the backbone of glycine and pre-proline. Knowledge of these interactions will improve current force-fields, and help understand structural motifs containing these residues. http://www.biomedcentral.com/1472-6807/5/14 Bosco K Ho and Robert Brasseur BMC Structural Biology 2005, 5:14 Number of accesses: 266 2005-08-16 doi:10.1186/1472-6807-5-14 BMC Structural Biology 1472-6807 5 14 2005-08-16 Background: The transcription factor NF-kappaB is a very interesting target molecule for the design on anti-tumor, anti-inflammatory and pro-apoptotic drugs. However, the application of the widely-used molecular docking computational method for the virtual screening of chemical libraries on NF-kappaB is not yet reported in literature. Docking studies on a dataset of 27 molecules from extracts of two different medicinal plants to NF-kappaB-p50 were performed with the purpose of developing a docking protocol fit for the target under study. Results: We enhanced the simple docking procedure by means of a sort of combined target- and ligand-based drug design approach. Advantages of this combination strategy, based on a similarity parameter for the identification of weak binding chemical entities, are illustrated in this work with the discovery of a new lead compound for NF-kappaB. Further biochemical analyses based on EMSA were performed and biological effects were tested on the compound exhibiting the best docking score. All experimental analysis were in fairly good agreement with molecular modeling findings. Conclusion: The results obtained sustain the concept that the docking performance is predictive of a biochemical activity. In this respect, this paper represents the first example of successfully individuation through molecular docking simulations of a promising lead compound for the inhibition of NF-kappaB-p50 biological activity and modulation of the expression of the NF-kB regulated IL8 gene. http://www.biomedcentral.com/1472-6807/8/38 Laura Piccagli, Enrica Fabbri, Monica Borgatti, Valentino Bezzerri, Irene Mancini, Elena Nicolis, Maria C Dechecchi, Ilaria Lampronti, Giulio Cabrini and Roberto Gambari BMC Structural Biology 2008, 8:38 Number of accesses: 253 2008-09-03 doi:10.1186/1472-6807-8-38 BMC Structural Biology 1472-6807 8 38 2008-09-03 Background: Circular dichroism spectroscopy is a widely used technique to analyze the secondary structure of proteins in solution. Predictive methods use the circular dichroism spectra from proteins of known tertiary structure to assess the secondary structure contents of a protein with unknown structure given its circular dichroism spectrum. Results: We developed K2D2, a method with an associated web server to estimate protein secondary structure from circular dichroism spectra. The method uses a self-organized map of spectra from proteins with known structure to deduce a map of protein secondary structure that is used to do the predictions. Conclusion: The K2D2 server is publicly accessible at http://www.ogic.ca/projects/k2d2/. It accepts as input a circular dichroism spectrum and outputs the estimated secondary structure content (alpha-helix and beta-strand) of the corresponding protein, as well as an estimated measure of error. http://www.biomedcentral.com/1472-6807/8/25 Carolina Perez-Iratxeta and Miguel A Andrade-Navarro BMC Structural Biology 2008, 8:25 Number of accesses: 251 2008-05-13 doi:10.1186/1472-6807-8-25 BMC Structural Biology 1472-6807 8 25 2008-05-13 Background: In search of new antifungal targets of potential interest for pharmaceutical companies, we initiated a comparative genomics study to identify the most promising protein-coding genes in fungal genomes. One criterion was the protein sequence conservation between reference pathogenic genomes. A second criterion was that the corresponding gene in Saccharomyces cerevisiae should be essential. Since thiamine pyrophosphate is an essential product involved in a variety of metabolic pathways, proteins responsible for its production satisfied these two criteria. Results: We report the enzymatic characterization and the crystallographic structure of the Candida albicans Thiamine pyrophosphokinase. The protein was co-crystallized with thiamine or thiamine-PNP. Conclusion: The presence of an inorganic phosphate in the crystallographic structure opposite the known AMP binding site relative to the thiamine moiety suggests that a second AMP molecule could be accommodated in the C. albicans structure. Together with the crystallographic structures of the enzyme/substrate complexes this suggests the existence of a secondary, less specific, nucleotide binding site in the Candida albicans thiamine pyrophosphokinase which could transiently serve during the release or the binding of ATP. The structures also highlight a conserved Glutamine residue (Q138) which could interact with the ATP α-phosphate and act as gatekeeper. Finally, the TPK/Thiamine-PNP complex is consistent with a one step mechanism of pyrophosphorylation. http://www.biomedcentral.com/1472-6807/8/33 Sébastien Santini, Vincent Monchois, Nicolas Mouz, Cécile Sigoillot, Tristan Rousselle, Jean-Michel Claverie and Chantal Abergel BMC Structural Biology 2008, 8:33 Number of accesses: 251 2008-07-24 doi:10.1186/1472-6807-8-33 BMC Structural Biology 1472-6807 8 33 2008-07-24