PBxplore: a tool to analyze local protein structure and deformability with Protein Blocks

This paper describes the development and application of a suite of tools, called PBxplore, to analyze the dynamics and deformability of protein structures using Protein Blocks (PBs). Proteins are highly dynamic macromolecules, and a classical way to analyze their inherent flexibility is to perform molecular dynamics simulations. The advantage of using small structural prototypes such as PBs is to give a good approximation of the local structure of the protein backbone. More importantly, by reducing the conformational complexity of protein structures, PBs allow analysis of local protein deformability which cannot be done with other methods and had been used efficiently in different applications. PBxplore is able to process large amounts of data such as those produced by molecular dynamics simulations. It produces frequencies, entropy and information logo outputs as text and graphics. PBxplore is available at https://github.com/pierrepo/PBxplore and is released under the open-source MIT license

Protein lipograms

Linguistic analysis of protein sequences is an underexploited technique. Here, we capitalize on the concept of the lipogram to characterize sequences at the proteome levels. A lipogram is a literary composition which omits one or more letters. A protein lipogram likewise omits one or more types of amino acid. In this article, we establish a usable terminology for the decomposition of a sequence collection in terms of the lipogram. Next, we characterize Uniref50 using a lipogram decomposition. At the global level, protein lipograms exhibit power-law properties. A clear correlation with metabolic cost is seen. Finally, we use the lipogram construction to assign proteomes to the four branches of the tree-of-life: archaea, bacteria, eukaryotes and viruses. We conclude from this pilot study that the lipogram demonstrates considerable potential as an additional tool for sequence analysis and proteome classification

ProteomeScout: A repository and analysis resource for post-translational modifications and proteins

ProteomeScout (https://proteomescout.wustl.edu) is a resource for the study of proteins and their post-translational modifications (PTMs) consisting of a database of PTMs, a repository for experimental data, an analysis suite for PTM experiments, and a tool for visualizing the relationships between complex protein annotations. The PTM database is a compendium of public PTM data, coupled with user-uploaded experimental data. ProteomeScout provides analysis tools for experimental datasets, including summary views and subset selection, which can identify relationships within subsets of data by testing for statistically significant enrichment of protein annotations. Protein annotations are incorporated in the ProteomeScout database from external resources and include terms such as Gene Ontology annotations, domains, secondary structure and non-synonymous polymorphisms. These annotations are available in the database download, in the analysis tools and in the protein viewer. The protein viewer allows for the simultaneous visualization of annotations in an interactive web graphic, which can be exported in Scalable Vector Graphics (SVG) format. Finally, quantitative data measurements associated with public experiments are also easily viewable within protein records, allowing researchers to see how PTMs change across different contexts. ProteomeScout should prove useful for protein researchers and should benefit the proteomics community by providing a stable repository for PTM experiments

Novel Intersubunit Interaction Critical for HIV-1 Core Assembly Defines a Potentially Targetable Inhibitor Binding Pocket

HIV-1 capsid protein (CA) plays critical roles in both early and late stages of the viral replication cycle. Mutagenesis and structural experiments have revealed that capsid core stability significantly affects uncoating and initiation of reverse transcription in host cells. This has led to efforts in developing antivirals targeting CA and its assembly, although none of the currently identified compounds are used in the clinic for treatment of HIV infection. A specific interaction that is primarily present in pentameric interfaces in the HIV-1 capsid core was identified and is reported to be important for CA assembly. This is shown by multidisciplinary characterization of CA site-directed mutants using biochemical analysis of virus-like particle formation, transmission electron microscopy of in vitro assembly, crystallographic studies, and molecular dynamic simulations. The data are consistent with a model where a hydrogen bond between CA residues E28 and K30′ from neighboring N-terminal domains (CA_(NTD)s) is important for CA pentamer interactions during core assembly. This pentamer-preferred interaction forms part of an N-terminal domain interface (NDI) pocket that is amenable to antiviral targeting

Możliwość stosowania narzędzi modelowania ewakuacji dla taboru kolejowego

Evacuation modelling technology offers designers and regulators of train new opportunities to rigorously test designs and theories in order to improve the passengers’ safety. This paper deals with the opportunity to use these tools for the railway industry. The FDS+Evac and buildingEXODUS softwares are used to model and simulate the evacuation of rolling stock. Firstly, in order to demonstrate the reliability of these tools to calculate the complete evacuation time, a comparative study was achieved between a real test, simulations done with FDS+Evac and simulations done with buildingEXODUS. Multiple simulations are performed to capture the stochastic variations in egress times. The philosophy of this comparative study is to realize the real test in one hand, and to use evacuation modelling tools with the incoming data (population, train geometry, initial position of the people, and known characteristics of the population) of the real test in another hand. The goal is not to stall the simulations results with the real test but to analyze the results of calculations by themselves. The following study highlights the interest of using evacuation modelling for the railway industry and shows their reliability in order to satisfy the TSI RST HS 2008/232/CE and the future TSI LOC&PAS. A confrontation „modelling – full-scale test” is presented and analysed.Technika modelowania ewakuacji daje konstruktorom i ciałom nadzorującym pociągi nowe możliwości rygorystycznego sprawdzenie konstrukcji i teorii tak, aby poprawić bezpieczeństwo pasażerów. W artykule omówiono możliwość zastosowania tych narzędzi w kolejnictwie. Do modelowania i symulacji ewakuacji pasażerów z taboru kolejowego stosuje się programy komputerowe FDS+Evac oraz buildingEXODUS. Po pierwsze, dla zademonstrowania niezawodności tych narzędzi do obliczenia całkowitego czasu ewakuacji, dokonano analizy porównawczej dla próby rzeczywistej, symulacji przeprowadzonej za pomocą FDS+Evac i za pomocą buildingEXODUS. Wykonano symulacje wielokrotne w celu uchwycenia wariacji stochastycznych czasów wyjścia. Intencją tej analizy porównawczej jest z jednej strony reali-zacja próby rzeczywistej, a z drugiej strony użycie narzędzi modelowania ewakuacji z wykorzystaniem danych pochodzących z prób rzeczywistych (liczba osób, geometria pociągu, położenie początkowe osób, znana charakterystyka populacji osób). Celem nie jest tu konfrontacja wyników symulacji i wyników próby rzeczywistej, ale analiza wyników obliczeń jako takich. Wykonana następnie analiza podkreśla zainteresowanie modelowaniem ewakuacji w kolejnictwie i pokazuje jego wiarygodność przy spełnieniu normy TSI RST HS 2008/232/CE i przyszłej TSI LOC&PAS. Przedstawiono i przeanalizowano zestawienie „Modelowanie – próba w skali naturalnej