36,500 research outputs found
Integrating sequence and structural biology with DAS.
BACKGROUND: The Distributed Annotation System (DAS) is a network protocol for exchanging biological data. It is frequently used to share annotations of genomes and protein sequence. RESULTS: Here we present several extensions to the current DAS 1.5 protocol. These provide new commands to share alignments, three dimensional molecular structure data, add the possibility for registration and discovery of DAS servers, and provide a convention how to provide different types of data plots. We present examples of web sites and applications that use the new extensions. We operate a public registry of DAS sources, which now includes entries for more than 250 distinct sources. CONCLUSION: Our DAS extensions are essential for the management of the growing number of services and exchange of diverse biological data sets. In addition the extensions allow new types of applications to be developed and scientific questions to be addressed. The registry of DAS sources is available at http://www.dasregistry.org.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are
Serverification of Molecular Modeling Applications: the Rosetta Online Server that Includes Everyone (ROSIE)
The Rosetta molecular modeling software package provides experimentally
tested and rapidly evolving tools for the 3D structure prediction and
high-resolution design of proteins, nucleic acids, and a growing number of
non-natural polymers. Despite its free availability to academic users and
improving documentation, use of Rosetta has largely remained confined to
developers and their immediate collaborators due to the code's difficulty of
use, the requirement for large computational resources, and the unavailability
of servers for most of the Rosetta applications. Here, we present a unified web
framework for Rosetta applications called ROSIE (Rosetta Online Server that
Includes Everyone). ROSIE provides (a) a common user interface for Rosetta
protocols, (b) a stable application programming interface for developers to add
additional protocols, (c) a flexible back-end to allow leveraging of computer
cluster resources shared by RosettaCommons member institutions, and (d)
centralized administration by the RosettaCommons to ensure continuous
maintenance. This paper describes the ROSIE server infrastructure, a
step-by-step 'serverification' protocol for use by Rosetta developers, and the
deployment of the first nine ROSIE applications by six separate developer
teams: Docking, RNA de novo, ERRASER, Antibody, Sequence Tolerance,
Supercharge, Beta peptide design, NCBB design, and VIP redesign. As illustrated
by the number and diversity of these applications, ROSIE offers a general and
speedy paradigm for serverification of Rosetta applications that incurs
negligible cost to developers and lowers barriers to Rosetta use for the
broader biological community. ROSIE is available at
http://rosie.rosettacommons.org
XML in Motion from Genome to Drug
Information technology (IT) has emerged as a central to the solution of contemporary genomics and drug discovery problems. Researchers involved in genomics, proteomics, transcriptional profiling, high throughput structure determination, and in other sub-disciplines of bioinformatics have direct impact on this IT revolution. As the full genome sequences of many species, data from structural genomics, micro-arrays, and proteomics became available, integration of these data to a common platform require sophisticated bioinformatics tools. Organizing these data into knowledgeable databases and developing appropriate software tools for analyzing the same are going to be major challenges. XML (eXtensible Markup Language) forms the backbone of biological data representation and exchange over the internet, enabling researchers to aggregate data from various heterogeneous data resources. The present article covers a comprehensive idea of the integration of XML on particular type of biological databases mainly dealing with sequence-structure-function relationship and its application towards drug discovery. This e-medical science approach should be applied to other scientific domains and the latest trend in semantic web applications is also highlighted
Ab initio RNA folding
RNA molecules are essential cellular machines performing a wide variety of
functions for which a specific three-dimensional structure is required. Over
the last several years, experimental determination of RNA structures through
X-ray crystallography and NMR seems to have reached a plateau in the number of
structures resolved each year, but as more and more RNA sequences are being
discovered, need for structure prediction tools to complement experimental data
is strong. Theoretical approaches to RNA folding have been developed since the
late nineties when the first algorithms for secondary structure prediction
appeared. Over the last 10 years a number of prediction methods for 3D
structures have been developed, first based on bioinformatics and data-mining,
and more recently based on a coarse-grained physical representation of the
systems. In this review we are going to present the challenges of RNA structure
prediction and the main ideas behind bioinformatic approaches and physics-based
approaches. We will focus on the description of the more recent physics-based
phenomenological models and on how they are built to include the specificity of
the interactions of RNA bases, whose role is critical in folding. Through
examples from different models, we will point out the strengths of
physics-based approaches, which are able not only to predict equilibrium
structures, but also to investigate dynamical and thermodynamical behavior, and
the open challenges to include more key interactions ruling RNA folding.Comment: 28 pages, 18 figure
Structure- and context-based analysis of the GxGYxYP family reveals a new putative class of glycoside hydrolase.
BackgroundGut microbiome metagenomics has revealed many protein families and domains found largely or exclusively in that environment. Proteins containing the GxGYxYP domain are over-represented in the gut microbiota, and are found in Polysaccharide Utilization Loci in the gut symbiont Bacteroides thetaiotaomicron, suggesting their involvement in polysaccharide metabolism, but little else is known of the function of this domain.ResultsGenomic context and domain architecture analyses support a role for the GxGYxYP domain in carbohydrate metabolism. Sparse occurrences in eukaryotes are the result of lateral gene transfer. The structure of the GxGYxYP domain-containing protein encoded by the BT2193 locus reveals two structural domains, the first composed of three divergent repeats with no recognisable homology to previously solved structures, the second a more familiar seven-stranded β/α barrel. Structure-based analyses including conservation mapping localise a presumed functional site to a cleft between the two domains of BT2193. Matching to a catalytic site template from a GH9 cellulase and other analyses point to a putative catalytic triad composed of Glu272, Asp331 and Asp333.ConclusionsWe suggest that GxGYxYP-containing proteins constitute a novel glycoside hydrolase family of as yet unknown specificity
Die Rolle der Zielnähe und der investierten Anstrengung für den erwarteten Wert einer Handlung
In human neuroscientific research, there has been an increasing interest in how the brain computes the value of an anticipated outcome. However, evidence is still missing about which valuation related brain regions are modulated by the proximity to an expected goal and the previously invested effort to reach a goal. The aim of this dissertation is to investigate the effects of goal proximity and invested effort on valuation related regions in the human brain. We addressed this question in two fMRI studies by integrating a commonly used reward anticipation task in differential versions of a Multitrial Reward Schedule Paradigm. In both experiments, subjects had to perform consecutive reward anticipation tasks under two different reward contingencies: in the delayed condition, participants received a monetary reward only after successful completion of multiple consecutive trials. In the immediate condition, money was earned after every successful trial. In the first study, we could demonstrate that the rostral cingulate zone of the posterior medial frontal cortex signals action value contingent to goal proximity, thereby replicating neurophysiological findings about goal proximity signals in a homologous region in non-human primates. The findings of the second study imply that brain regions associated with general cognitive control processes are modulated by previous effort investment. Furthermore, we found the posterior lateral prefrontal cortex and the orbitofrontal cortex to be involved in coding for the effort-based context of a situation. In sum, these results extend the role of the human rostral cingulate zone in outcome evaluation to the continuous updating of action values over a course of action steps based on the proximity to the expected reward. Furthermore, we tentatively suggest that previous effort investment invokes processes under the control of the executive system, and that posterior lateral prefrontal cortex and the orbitofrontal cortex are involved in an effort-based context representation that can be used for outcome evaluation that is dependent on the characteristics of the current situation.Derzeit besteht im Bereich der Neurowissenschaften ein großes Interesse daran aufzuklären, auf welche Weise verschiedene Variablen die Wertigkeit eines erwarteten Handlungsziels beeinflussen bzw. welche Hirnregionen an der Repräsentation der Wertigkeit eines Handlungsziels beteiligt sind. Die meisten Untersuchungen beziehen sich dabei auf Einflussgrößen wie die erwartete Belohnungshöhe, die Wahrscheinlichkeit, mit der ein bestimmtes Ereignis eintritt, oder die Dauer bis zum Erhalt einer Belohnung. Bisher liegen jedoch kaum Untersuchungen vor bezüglich zweier anderer Variablen, die ebenfalls den erwarteten Wert eines Handlungsergebnisses beeinflussen. Das sind (a) die Nähe zu dem erwarteten Ziel und (b) die bisher investierte Anstrengung, um ein Ziel zu erreichen. Das Ziel der vorliegenden Dissertation ist zu untersuchen, wie die Nähe zum Ziel und die bisher investierte Anstrengung Gehirnregionen beeinflussen, die mit der Repräsentation von Wertigkeit im Zusammenhang stehen. Dazu führten wir zwei fMRT-Studien durch, in denen wir eine klassische Belohnungs-Antizipationsaufgabe in unterschiedliche Versionen eines „Multitrial Reward Schedule“ Paradigmas integriert haben. Das bedeutet, dass die Probanden Belohnungs-Antizipationsaufgaben unter zwei unterschiedlichen Belohnungskontingenzen bearbeiteten: In der verzögerten Bedingung erhielten die Probanden einen Geldbetrag nach der erfolgreichen Bearbeitung von mehreren aufeinanderfolgenden Aufgaben, in der direkten Bedingung dagegen nach jeder korrekt ausgeführten Aufgabe. In der ersten Studie konnte eine sukzessiv ansteigende Aktivität in Abhängigkeit zur Zielnähe in der rostralen cingulären Zone identifiziert werden. Das deutet darauf hin, dass dieses Areal den Wert einer Handlung in Abhängigkeit zur Nähe zum Ziel kodiert. Die Ergebnisse der zweiten Studie zeigten, dass die bisher investierte Anstrengung kortikale Regionen moduliert, die klassischerweise mit kognitiven Kontrollfunktionen in Zusammenhang gebracht werden. Außerdem repräsentierten der posteriore laterale präfrontale Cortex und der orbitofrontale Cortex den motivationalen Kontext eines Trials anhand des Risikos des Verlustes von bisher investierter Anstrengung. Insgesamt weisen diese Befunde darauf hin, dass die rostrale cinguläre Zone eine entscheidende Rolle spielt für die Kontrolle sequenzieller Handlungsstufen, die auf eine verzögerte Belohnung ausgerichtet sind. Diese Kontrollfunktion scheint auf der kontinuierlichen Aktualisierung des Wertes einer Handlungsstufe zu basieren, der von der aktuellen Zielnähe bestimmt wird. Die Befunde der zweiten Studie lassen darauf schließen, dass sich die bisher investierte Anstrengung zur Erreichung eines Handlungsziels auf die Bereitstellung von allgemeinen kognitiven Ressourcen auswirkt. Das Risiko des Verlustes von bisher investierter Anstrengung kann außerdem ein kontextuelles Merkmal der Situation darstellen, das als Bezugsrahmen für die Evaluation des erwarteten Wertes dienen kann
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