Protein Peeling 2: a web server to convert protein structures into series of protein units

Protein Peeling 2 (PP2) is a web server for the automatic identification of protein units (PUs) given the 3D coordinates of a protein. PUs are an intermediate level of protein structure description between protein domains and secondary structures. It is a new tool to better understand and analyze the organization of protein structures. PP2 uses only the matrices of protein contact probabilities and cuts the protein structures optimally using Matthews' coefficient correlation. An index assesses the compactness quality of each PU. Results are given both textually and graphically using JMol and PyMol softwares. The server can be accessed from

Helioseismology with PICARD

PICARD is a CNES micro-satellite launched in June 2010 (Thuillier at al. 2006). Its main goal is to measure the solar shape, total and spectral irradiance during the ascending phase of the activity cycle. The SODISM telescope onboard PICARD also allows us to conduct a program for helioseismology in intensity at 535.7 nm (Corbard et al. 2008). One-minute cadence low-resolution full images are available for a so-called medium-$l$ program, and high-resolution images of the limb recorded every 2 minutes are used to study mode amplification near the limb in the perspective of g-mode search. First analyses and results from these two programs are presented here.Comment: 6 pages, 6 figures, Eclipse on the Coral Sea: Cycle 24 Ascending, GONG 2012 / LWS/SDO-5 / SOHO 27, November 12 - 16, 2012, Palm Cove, Queensland. Accepted for publication in Journal of Physics Conference Series on March 1st 201

KNOTTIN: the knottin or inhibitor cystine knot scaffold in 2007

The KNOTTIN database provides standardized information on the small disulfide-rich proteins with a knotted topology called knottins or inhibitor cystine knots. Static pages present the essential historical or recent results about knottin discoveries, sequences, structures, syntheses, folding, functions, applications and bibliography. New tools, KNOTER3D and KNOTER1D, are provided to determine or predict if a user query (3D structure or sequence) is a knottin. These tools are now used to automate the database update. All knottin structures and sequences in the database are now standardized according to the knottin nomenclature based on loop lengths between knotted cysteines, and to the knottin numbering scheme. Therefore, the whole KNOTTIN database (sequences and structures) can now be searched using loop lengths, in addition to keyword and sequence (BLAST, HMMER) searches. Renumbered and structurally fitted knottin PDB files are available for download as well as renumbered sequences, sequence alignments and logos. The knottin numbering scheme is used for automatic drawing of standardized two-dimensional Colliers de Perles of any knottin structure or sequence in the database or provided by the user. The KNOTTIN database is available at http://knottin.cbs.cnrs.fr

MitoGenesisDB: an expression data mining tool to explore spatio-temporal dynamics of mitochondrial biogenesis

Mitochondria constitute complex and flexible cellular entities, which play crucial roles in normal and pathological cell conditions. The database MitoGenesisDB focuses on the dynamic of mitochondrial protein formation through global mRNA analyses. Three main parameters confer a global view of mitochondrial biogenesis: (i) time-course of mRNA production in highly synchronized yeast cell cultures, (ii) microarray analyses of mRNA localization that define translation sites and (iii) mRNA transcription rate and stability which characterize genes that are more dependent on post-transcriptional regulation processes. MitoGenesisDB integrates and establishes cross-comparisons between these data. Several model organisms can be analyzed via orthologous relationships between interspecies genes. More generally this database supports the ‘post-transcriptional operon’ model, which postulates that eukaryotes co-regulate related mRNAs based on their functional organization in ribonucleoprotein complexes. MitoGenesisDB allows identifying such groups of post-trancriptionally regulated genes and is thus a useful tool to analyze the complex relationships between transcriptional and post-transcriptional regulation processes. The case of respiratory chain assembly factors illustrates this point. The MitoGenesisDB interface is available at http://www.dsimb.inserm.fr/dsimb_tools/mitgene/

About the p-mode frequency shifts in HD 49933

We study the frequency dependence of the frequency shifts of the low-degree p modes measured in the F5V star HD 49933, by analyzing the second run of observations collected by the CoRoT satellite. The 137-day light curve is divided into two subseries corresponding to periods of low and high stellar activity. The activity-frequency relationship is obtained independently from the analysis of the mode frequencies extracted by both a local and a global peak-fitting analyses, and from a cross-correlation technique in the frequency range between 1450 microHz and 2500 microHz. The three methods return consistent results. We show that the frequency shifts measured in HD 49933 present a frequency dependence with a clear increase with frequency, reaching a maximal shift of about 2 microHz around 2100 microHz. Similar variations are obtained between the l=0 and l=1 modes. At higher frequencies, the frequency shifts show indications of a downturn followed by an upturn, consistent between the l=0 and 1 modes. We show that the frequency variation of the p-mode frequency shifts of the solar-like oscillating star HD 49933 has a comparable shape to the one observed in the Sun, which is understood to arise from changes in the outer layers due to its magnetic activity.Comment: 5 pages, 3 figures, 1 table, Accepted for publication in A\&

Asteroseismology of Procyon with SOPHIE

This paper reports a 9-night asteroseismic observation program conducted in January 2007 with the new spectrometer Sophie at the OHP 193-cm telescope, on the F5 IV-V target Procyon A. This first asteroseismic program with Sophie was intended to test the performance of the instrument with a bright but demanding asteroseismic target and was part of a multisite network. The Sophie spectra have been reduced with the data reduction software provided by OHP. The Procyon asteroseismic data were then analyzed with statistical tools. The asymptotic analysis has been conducted considering possible curvature in the echelle diagram analysis. These observations have proven the efficient performance of Sophie used as an asteroseismometer, and succeed in a clear detection of the large spacing. An \'echelle diagram based on the 54-$\mu$Hz spacing shows clear ridges. Identification of the peaks exhibits large spacings varying from about 52 $\mu$Hz to 56 $\mu$Hz.Comment: 7 pages, 7 figure

CyBase: a database of cyclic protein sequences and structures, with applications in protein discovery and engineering

CyBase was originally developed as a database for backbone-cyclized proteins, providing search and display capabilities for sequence, structure and function data. Cyclic proteins are interesting because, compared to conventional proteins, they have increased stability and enhanced binding affinity and therefore can potentially be developed as protein drugs. The new CyBase release features a redesigned interface and internal architecture to improve user-interactivity, collates double the amount of data compared to the initial release, and hosts a novel suite of tools that are useful for the visualization, characterization and engineering of cyclic proteins. These tools comprise sequence/structure 2D representations, a summary of grafting and mutation studies of synthetic analogues, a study of N- to C-terminal distances in known protein structures and a structural modelling tool to predict the best linker length to cyclize a protein. These updates are useful because they have the potential to help accelerate the discovery of naturally occurring cyclic proteins and the engineering of cyclic protein drugs. The new release of CyBase is available at http://research1t.imb.uq.edu.au/cybas

Optimizing structural modeling for a specific protein scaffold: knottins or inhibitor cystine knots

<p>Abstract</p> <p>Background</p> <p>Knottins are small, diverse and stable proteins with important drug design potential. They can be classified in 30 families which cover a wide range of sequences (1621 sequenced), three-dimensional structures (155 solved) and functions (> 10). Inter knottin similarity lies mainly between 15% and 40% sequence identity and 1.5 to 4.5 Å backbone deviations although they all share a tightly knotted disulfide core. This important variability is likely to arise from the highly diverse loops which connect the successive knotted cysteines. The prediction of structural models for all knottin sequences would open new directions for the analysis of interaction sites and to provide a better understanding of the structural and functional organization of proteins sharing this scaffold.</p> <p>Results</p> <p>We have designed an automated modeling procedure for predicting the three-dimensionnal structure of knottins. The different steps of the homology modeling pipeline were carefully optimized relatively to a test set of knottins with known structures: template selection and alignment, extraction of structural constraints and model building, model evaluation and refinement. After optimization, the accuracy of predicted models was shown to lie between 1.50 and 1.96 Å from native structures at 50% and 10% maximum sequence identity levels, respectively. These average model deviations represent an improvement varying between 0.74 and 1.17 Å over a basic homology modeling derived from a unique template. A database of 1621 structural models for all known knottin sequences was generated and is freely accessible from our web server at <url>http://knottin.cbs.cnrs.fr</url>. Models can also be interactively constructed from any knottin sequence using the structure prediction module Knoter1D3D available from our protein analysis toolkit PAT at <url>http://pat.cbs.cnrs.fr</url>.</p> <p>Conclusions</p> <p>This work explores different directions for a systematic homology modeling of a diverse family of protein sequences. In particular, we have shown that the accuracy of the models constructed at a low level of sequence identity can be improved by 1) a careful optimization of the modeling procedure, 2) the combination of multiple structural templates and 3) the use of conserved structural features as modeling restraints.</p

Warm-Start AlphaZero Self-Play Search Enhancements

Recently, AlphaZero has achieved landmark results in deep reinforcement learning, by providing a single self-play architecture that learned three different games at super human level. AlphaZero is a large and complicated system with many parameters, and success requires much compute power and fine-tuning. Reproducing results in other games is a challenge, and many researchers are looking for ways to improve results while reducing computational demands. AlphaZero's design is purely based on self-play and makes no use of labeled expert data ordomain specific enhancements; it is designed to learn from scratch. We propose a novel approach to deal with this cold-start problem by employing simple search enhancements at the beginning phase of self-play training, namely Rollout, Rapid Action Value Estimate (RAVE) and dynamically weighted combinations of these with the neural network, and Rolling Horizon Evolutionary Algorithms (RHEA). Our experiments indicate that most of these enhancements improve the performance of their baseline player in three different (small) board games, with especially RAVE based variants playing strongly