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1.
Background
Targeting conserved proteins of bacteria through antibacterial medications has resulted in both the development of resistant strains and changes to human health by destroying beneficial microbes which eventually become breeding grounds for the evolution of resistances. Despite the availability of more than 800 genomes sequences, 430 pathways, 4743 enzymes, 9257 metabolic reactions and protein (three-dimensional) 3D structures in bacteria, no pathogen-specific computational drug target identification tool has been developed.Methods
A web server, UniDrug-Target, which combines bacterial biological information and computational methods to stringently identify pathogen-specific proteins as drug targets, has been designed. Besides predicting pathogen-specific proteins essentiality, chokepoint property, etc., three new algorithms were developed and implemented by using protein sequences, domains, structures, and metabolic reactions for construction of partial metabolic networks (PMNs), determination of conservation in critical residues, and variation analysis of residues forming similar cavities in proteins sequences. First, PMNs are constructed to determine the extent of disturbances in metabolite production by targeting a protein as drug target. Conservation of pathogen-specific protein''s critical residues involved in cavity formation and biological function determined at domain-level with low-matching sequences. Last, variation analysis of residues forming similar cavities in proteins sequences from pathogenic versus non-pathogenic bacteria and humans is performed.Results
The server is capable of predicting drug targets for any sequenced pathogenic bacteria having fasta sequences and annotated information. The utility of UniDrug-Target server was demonstrated for Mycobacterium tuberculosis (H37Rv). The UniDrug-Target identified 265 mycobacteria pathogen-specific proteins, including 17 essential proteins which can be potential drug targets.Conclusions/Significance
UniDrug-Target is expected to accelerate pathogen-specific drug targets identification which will increase their success and durability as drugs developed against them have less chance to develop resistances and adverse impact on environment. The server is freely available at http://117.211.115.67/UDT/main.html. The standalone application (source codes) is available at http://www.bioinformatics.org/ftp/pub/bioinfojuit/UDT.rar. 相似文献2.
Background
Heme-copper oxygen reductases (HCOs) are the last enzymatic complexes of most aerobic respiratory chains, reducing dioxygen to water and translocating up to four protons across the inner mitochondrial membrane (eukaryotes) or cytoplasmatic membrane (prokaryotes). The number of completely sequenced genomes is expanding exponentially, and concomitantly, the number and taxonomic distribution of HCO sequences. These enzymes were initially classified into three different types being this classification recently challenged.Methodology
We reanalyzed the classification scheme and developed a new bioinformatics classifier for the HCO and Nitric oxide reductases (NOR), which we benchmark against a manually derived gold standard sequence set. It is able to classify any given sequence of subunit I from HCO and NOR with a global recall and precision both of 99.8%. We use this tool to classify this protein family in 552 completely sequenced genomes.Conclusions
We concluded that the new and broader data set supports three functional and evolutionary groups of HCOs. Homology between NORs and HCOs is shown and NORs closest relationship with C Type HCOs demonstrated. We established and made available a classification web tool and an integrated Heme-Copper Oxygen reductase and NOR protein database (www.evocell.org/hco). 相似文献3.
Salmonellosis is one of the most common and widely distributed food borne diseases caused by Salmonella serovars. The
emergence of multi drug resistant strains has become a threatening public health problem and targeting unique effectors of this
pathogen can be considered as a powerful strategy for drug design. SalmonellaBase is an online web portal serving as an integrated
source of information about Salmonella serovars with the data required for the structural and functional studies and the analysis of
druggable targets in Salmonella. We have identified several target proteins, which helps in the pathogenicity of the organism and
predicted their structures. The database will have the information on completely sequenced genomes of Salmonella species with
the complete set of protein sequences of the respective strains, determined structures, predicted protein structures and biochemical
pathways of the respective strains. In addition, we have provided information about name and source of the protein, Uniprot and
Protein Data Bank codes and literature information. Furthermore, SalmonellaBase is linked to related databases and other
resources. We have set up a web interface with different search and display options so that users have the ability to get the data in
several ways. SalmonellaBase is a freely available database.
Availability
http://www.salmonellabase.com/ 相似文献4.
jMOTU and Taxonerator: turning DNA Barcode sequences into annotated operational taxonomic units 总被引:1,自引:0,他引:1
Background
DNA barcoding and other DNA sequence-based techniques for investigating and estimating biodiversity require explicit methods for associating individual sequences with taxa, as it is at the taxon level that biodiversity is assessed. For many projects, the bioinformatic analyses required pose problems for laboratories whose prime expertise is not in bioinformatics. User-friendly tools are required for both clustering sequences into molecular operational taxonomic units (MOTU) and for associating these MOTU with known organismal taxonomies.Results
Here we present jMOTU, a Java program for the analysis of DNA barcode datasets that uses an explicit, determinate algorithm to define MOTU. We demonstrate its usefulness for both individual specimen-based Sanger sequencing surveys and bulk-environment metagenetic surveys using long-read next-generation sequencing data. jMOTU is driven through a graphical user interface, and can analyse tens of thousands of sequences in a short time on a desktop computer. A companion program, Taxonerator, that adds traditional taxonomic annotation to MOTU, is also presented. Clustering and taxonomic annotation data are stored in a relational database, and are thus amenable to subsequent data mining and web presentation.Conclusions
jMOTU efficiently and robustly identifies the molecular taxa present in survey datasets, and Taxonerator decorates the MOTU with putative identifications. jMOTU and Taxonerator are freely available from http://www.nematodes.org/. 相似文献5.
Edward G. Hawkins Ian Martin Lindsay M. Kondo Meredith E. Judy Victoria E. Brings Chung-Lung Chan GinaMari G. Blackwell Jill C. Bettinger Andrew G. Davies 《Genetics》2015,199(1):135-149
The Prp43 DExD/H-box protein is required for progression of the biochemically distinct pre-messenger RNA and ribosomal RNA (rRNA) maturation pathways. In Saccharomyces cerevisiae, the Spp382/Ntr1, Sqs1/Pfa1, and Pxr1/Gno1 proteins are implicated as cofactors necessary for Prp43 helicase activation during spliceosome dissociation (Spp382) and rRNA processing (Sqs1 and Pxr1). While otherwise dissimilar in primary sequence, these Prp43-binding proteins each contain a short glycine-rich G-patch motif required for function and thought to act in protein or nucleic acid recognition. Here yeast two-hybrid, domain-swap, and site-directed mutagenesis approaches are used to investigate G-patch domain activity and portability. Our results reveal that the Spp382, Sqs1, and Pxr1 G-patches differ in Prp43 two-hybrid response and in the ability to reconstitute the Spp382 and Pxr1 RNA processing factors. G-patch protein reconstitution did not correlate with the apparent strength of the Prp43 two-hybrid response, suggesting that this domain has function beyond that of a Prp43 tether. Indeed, while critical for Pxr1 activity, the Pxr1 G-patch appears to contribute little to the yeast two-hybrid interaction. Conversely, deletion of the primary Prp43 binding site within Pxr1 (amino acids 102–149) does not impede rRNA processing but affects small nucleolar RNA (snoRNA) biogenesis, resulting in the accumulation of slightly extended forms of select snoRNAs, a phenotype unexpectedly shared by the prp43 loss-of-function mutant. These and related observations reveal differences in how the Spp382, Sqs1, and Pxr1 proteins interact with Prp43 and provide evidence linking G-patch identity with pathway-specific DExD/H-box helicase activity. 相似文献
6.
Tom Baden Andre Maia Chagas Greg Gage Timothy Marzullo Lucia L. Prieto-Godino Thomas Euler 《PLoS biology》2015,13(3)
The introduction of affordable, consumer-oriented 3-D printers is a milestone in the current “maker movement,” which has been heralded as the next industrial revolution. Combined with free and open sharing of detailed design blueprints and accessible development tools, rapid prototypes of complex products can now be assembled in one’s own garage—a game-changer reminiscent of the early days of personal computing. At the same time, 3-D printing has also allowed the scientific and engineering community to build the “little things” that help a lab get up and running much faster and easier than ever before.Applications of 3-D printing technologies (Fig. 1A, Box 1) have become as diverse as the types of materials that can be used for printing. Replacement parts at the International Space Station may be printed in orbit from durable plastics or metals, while back on Earth the food industry is starting to explore the same basic technology to fold strings of chocolate into custom-shaped confectionary. Also, consumer-oriented laser-cutting technology makes it very easy to cut raw materials such as sheets of plywood, acrylic, or aluminum into complex shapes within seconds. The range of possibilities comes to light when those mechanical parts are combined with off-the-shelf electronics, low-cost microcontrollers like Arduino boards [1], and single-board computers such as a Beagleboard [2] or a Raspberry Pi [3]. After an initial investment of typically less than a thousand dollars (e.g., to set-up a 3-D printer), the only other materials needed to build virtually anything include a few hundred grams of plastic (approximately US$30/kg), cables, and basic electronic components [4,5].Open in a separate windowFig 1Examples of open 3-D printed laboratory tools.
A
1, Components for laboratory tools, such as the base for a micromanipulator [18] shown here, can be rapidly prototyped using 3-D printing. A
2, The printed parts can be easily combined with an off-the-shelf continuous rotation servo-motor (bottom) to motorize the main axis. B
1, A 3-D printable micropipette [8], designed in OpenSCAD [19], shown in full (left) and cross-section (right). B
2, The pipette consists of the printed parts (blue), two biro fillings with the spring, an off-the-shelf piece of tubing to fit the tip, and one screw used as a spacer. B
3, Assembly is complete with a laboratory glove or balloon spanned between the two main printed parts and sealed with tape to create an airtight bottom chamber continuous with the pipette tip. Accuracy is ±2–10 μl depending on printer precision, and total capacity of the system is easily adjusted using two variables listed in the source code, or accessed via the “Customizer” plugin on the thingiverse link [8]. See also the first table.Area Project Source Microscopy Smartphone Microscope
http://www.instructables.com/id/10-Smartphone-to-digital-microscope-conversion
iPad Microscope
http://www.thingiverse.com/thing:31632
Raspberry Pi Microscope
http://www.thingiverse.com/thing:385308
Foldscope
http://www.foldscope.com/
Molecular Biology Thermocycler (PCR)
http://openpcr.org/
Water bath
http://blog.labfab.cc/?p=47
Centrifuge
http://www.thingiverse.com/thing:151406
Dremelfuge
http://www.thingiverse.com/thing:1483
Colorometer
http://www.thingiverse.com/thing:73910
Micropipette
http://www.thingiverse.com/thing:255519
Gel Comb
http://www.thingiverse.com/thing:352873
Hot Plate
http://www.instructables.com/id/Programmable-Temperature-Controller-Hot-Plate/
Magnetic Stirrer
http://www.instructables.com/id/How-to-Build-a-Magnetic-Stirrer/
Electrophysiology Waveform Generator
http://www.instructables.com/id/Arduino-Waveform-Generator/
Open EEG
https://www.olimex.com/Products/EEG/OpenEEG/
Mobile ECG
http://mobilecg.hu/
Extracellular amplifier
https://backyardbrains.com/products/spikerBox
Micromanipulator
http://www.thingiverse.com/thing:239105
Open Ephys
http://open-ephys.org/
Other Syringe pump
http://www.thingiverse.com/thing:210756
Translational Stage
http://www.thingiverse.com/thing:144838
Vacuum pump
http://www.instructables.com/id/The-simplest-vacuum-pump-in-the-world/
Skinner Box
http://www.kscottz.com/open-skinner-box-pycon-2014/