467 research outputs found
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Predicting protein structures and structural annotation of proteomes
Protein structure prediction methods aim to predict the structures of proteins from their amino acid sequences, utilizing various computational algorithms. Structural genome annotation is the process of attaching biological information to every protein encoded within a genome via the production of three-dimensional protein models
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The FunFOLD2 server for the prediction of protein-ligand interactions
The FunFOLD2 server is a new independent server that integrates our novel proteinâligand binding site and quality assessment protocols for the prediction of protein function (FN) from sequence via structure. Our guiding principles were, first, to provide a simple unified resource to make our function prediction software easily accessible to all via a simple web interface and, second, to produce integrated output for predictions that can be easily interpreted. The server provides a clean web interface so that results can be viewed on a single page and interpreted by non-experts at a glance. The output for the prediction is an image of the top predicted tertiary structure annotated to indicate putative ligand-binding site residues. The results page also includes a list of the most likely binding site residues and the types of predicted ligands and their frequencies in similar structures. The proteinâligand interactions can also be interactively visualized in 3D using the Jmol plug-in. The raw machine readable data are provided for developers, which comply with the Critical Assessment of Techniques for Protein Structure Prediction data standards for FN predictions. The FunFOLD2 webserver is freely available to all at the following web site: http://www.reading.ac.uk/bioinf/FunFOLD/FunFOLD_form_2_0.html
Lock-in thermography as a tool for fatigue damage monitoring of composite structures
International audienceFatigue dimensioning of composite structures has become a great challenge in the aeronautic industry. The estimation of the fatigue limit requires time-consuming experimental campaigns: millions of mechanical cycles are applied to one studied sample until failure, for several load levels. The alternative discussed in the present paper is to monitor the self-heating of carbon/epoxy composites under a significantly reduced number of load cycles, in order to define fatigue damage indicators. The chosen approach is to use lock-in thermography, which makes it possible to analyse the first harmonics of the heating signal, not matter how noisy it might be
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The binding site distance test score: a robust method for the assessment of predicted protein binding sites
We propose a novel method for scoring the accuracy of
protein binding site predictions â the Binding-site Distance Test
(BDT) score. Recently, the Matthews Correlation Coefficient (MCC)
has been used to evaluate binding site predictions, both by developers
of new methods and by the assessors for the community wide
prediction experiment â CASP8. Whilst being a rigorous scoring
method, the MCC does not take into account the actual 3D location
of the predicted residues from the observed binding site. Thus, an
incorrectly predicted site that is nevertheless close to the observed
binding site will obtain an identical score to the same number of nonbinding
residues predicted at random. The MCC is somewhat affected
by the subjectivity of determining observed binding residues
and the ambiguity of choosing distance cutoffs. By contrast the BDT
method produces continuous scores ranging between 0 and 1, relating
to the distance between the predicted and observed residues.
Residues predicted close to the binding site will score higher than
those more distant, providing a better reflection of the true accuracy
of predictions. The CASP8 function predictions were evaluated using
both the MCC and BDT methods and the scores were compared.
The BDT was found to strongly correlate with the MCC
scores whilst also being less susceptible to the subjectivity of defining
binding residues. We therefore suggest that this new simple
score is a potentially more robust method for future evaluations of
protein-ligand binding site predictions
IntFOLD: an integrated server for modelling protein structures and functions from amino acid sequences
IntFOLD is an independent web server that integrates our leading methods for structure and function prediction. The server provides a simple unified interface that aims to make complex protein modelling data more accessible to life scientists. The server web interface is designed to be intuitive and integrates a complex set of quantitative data, so that 3D modelling results can be viewed on a single page and interpreted by non-expert modellers at a glance. The only required input to the server is an amino acid sequence for the target protein. Here we describe major performance and user interface updates to the server, which comprises an integrated pipeline of methods for: tertiary structure prediction, global and local 3D model quality assessment, disorder prediction, structural domain prediction, function prediction and modelling of protein-ligand interactions. The server has been independently validated during numerous CASP (Critical Assessment of Techniques for Protein Structure Prediction) experiments, as well as being continuously evaluated by the CAMEO (Continuous Automated Model Evaluation) project. The IntFOLD server is available at: http://www.reading.ac.uk/bioinf/IntFOLD
9.7 micrometer Silicate Absorption in a Damped Lyman-alpha Absorber at z=0.52
We report a detection of the 9.7 micrometer silicate absorption feature in a
damped Lyman-alpha (DLA) system at z_{abs} = 0.524 toward AO0235+164, using the
Infrared Spectrograph (IRS) onboard the Spitzer Space Telescope. The feature
shows a broad shallow profile over about 8-12 micrometers in the absorber rest
frame and appears to be > 15 sigma significant in equivalent width. The feature
is fit reasonably well by the silicate absorption profiles for laboratory
amorphous olivine or diffuse Galactic interstellar clouds. To our knowledge,
this is the first indication of 9.7 micrometer silicate absorption in a DLA. We
discuss potential implications of this finding for the nature of the dust in
quasar absorbers. Although the feature is relatively shallow (tau_{9.7} =
0.08-0.09), it is about 2 times deeper than expected from extrapolation of the
tau_{9.7} vs. E(B-V) relation known for diffuse Galactic interstellar clouds.
Further studies of the 9.7 micrometer silicate feature in quasar absorbers will
open a new window on the dust in distant galaxies.Comment: 4 pages, 2 figures, submitted to Astrophysical Journal Letters
(revised version including referee's comments
Functional analysis of Plasmodium falciparum subpopulations associated with artemisinin resistance in Cambodia
Background: Plasmodium falciparum malaria is one of the most widespread parasitic infections in humans and remains a leading global health concern. Malaria elimination efforts are threatened by the emergence and spread of resistance to artemisinin-based combination therapy, the first-line treatment of malaria. Promising molecular markers and pathways associated with artemisinin drug resistance have been identified, but the underlying molecular mechanisms of resistance remains unknown. The genomic data from early period of emergence of artemisinin resistance (2008â2011) was evaluated, with aim to define k13 associated genetic background in Cambodia, the country identified as epicentre of anti-malarial drug resistance, through characterization of 167 parasite isolates using a panel of 21,257 SNPs. Results: Eight subpopulations were identified suggesting a process of acquisition of artemisinin resistance consistent with an emergence-selection-diffusion model, supported by the shifting balance theory. Identification of population specific mutations facilitated the characterization of a core set of 57 background genes associated with artemisinin resistance and associated pathways. The analysis indicates that the background of artemisinin resistance was not acquired after drug pressure, rather is the result of fixation followed by selection on the daughter subpopulations derived from the ancestral population. Conclusions: Functional analysis of artemisinin resistance subpopulations illustrates the strong interplay between ubiquitination and cell division or differentiation in artemisinin resistant parasites. The relationship of these pathways with the P. falciparum resistant subpopulation and presence of drug resistance markers in addition to k13, highlights the major role of admixed parasite population in the diffusion of artemisinin resistant background. The diffusion of resistant genes in the Cambodian admixed population after selection resulted from mating of gametocytes of sensitive and resistant parasite populations. (RĂ©sumĂ© d'auteur
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The ModFOLD4 server for the quality assessment of 3D protein models
Once you have generated a 3D model of a protein,
how do you know whether it bears any resemblance
to the actual structure? To determine the usefulness
of 3D models of proteins, they must be assessed in
terms of their quality by methods that predict their
similarity to the native structure. The ModFOLD4
server is the latest version of our leading independent
server for the estimation of both the global and
local (per-residue) quality of 3D protein models. The
server produces both machine readable and graphical
output, providing users with intuitive visual
reports on the quality of predicted protein tertiary
structures. The ModFOLD4 server is freely available
to all at: http://www.reading.ac.uk/bioinf/ModFOLD/
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FunFOLDQA: a quality assessment tool for protein-ligand binding site residue predictions
The estimation of prediction quality is important because without quality measures, it is difficult to determine the usefulness of a prediction. Currently, methods for ligand binding site residue predictions are assessed in the function prediction category of the biennial Critical Assessment of Techniques for Protein Structure Prediction (CASP) experiment, utilizing the Matthews Correlation Coefficient (MCC) and Binding-site Distance Test (BDT) metrics. However, the assessment of ligand binding site predictions using such metrics requires the availability of solved structures with bound ligands. Thus, we have developed a ligand binding site quality assessment tool, FunFOLDQA, which utilizes protein feature analysis to predict ligand binding site quality prior to the experimental solution of the protein structures and their ligand interactions. The FunFOLDQA feature scores were combined using: simple linear combinations, multiple linear regression and a neural network. The neural network produced significantly better results for correlations to both the MCC and BDT scores, according to Kendallâs Ï, Spearmanâs Ï and Pearsonâs r correlation coefficients, when tested on both the CASP8 and CASP9 datasets. The neural network also produced the largest Area Under the Curve score (AUC) when Receiver Operator Characteristic (ROC) analysis was undertaken for the CASP8 dataset. Furthermore, the FunFOLDQA algorithm incorporating the neural network, is shown to add value to FunFOLD, when both methods are employed in combination. This results in a statistically significant improvement over all of the best server methods, the FunFOLD method (6.43%), and one of the top manual groups (FN293) tested on the CASP8 dataset. The FunFOLDQA method was also found to be competitive with the top server methods when tested on the CASP9 dataset. To the best of our knowledge, FunFOLDQA is the first attempt to develop a method that can be used to assess ligand binding site prediction quality, in the absence of experimental data
Scaling of the F_2 structure function in nuclei and quark distributions at x>1
We present new data on electron scattering from a range of nuclei taken in
Hall C at Jefferson Lab. For heavy nuclei, we observe a rapid falloff in the
cross section for , which is sensitive to short range contributions to the
nuclear wave-function, and in deep inelastic scattering corresponds to probing
extremely high momentum quarks. This result agrees with higher energy muon
scattering measurements, but is in sharp contrast to neutrino scattering
measurements which suggested a dramatic enhancement in the distribution of the
`super-fast' quarks probed at x>1. The falloff at x>1 is noticeably stronger in
^2H and ^3He, but nearly identical for all heavier nuclei.Comment: 5 pages, 4 figures, to be submitted to physical revie
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