AISMIG—an interactive server-side molecule image generator

Using a web browser without additional software and generating interactive high quality and high resolution images of bio-molecules is no longer a problem. Interactive visualization of 3D molecule structures by Internet browsers normally is not possible without additional software and the disadvantage of browser-based structure images (e.g. by a Java applet) is their low resolution. Scientists who want to generate 3D molecular images with high quality and high resolution (e.g. for publications or to render a molecule for a poster) therefore require separately installed software that is often not easy to use. The alternative concept is an interactive server-side rendering application that can be interfaced with any web browser. Thus it combines the advantage of the web application with the high-end rendering of a raytracer. This article addresses users who want to generate high quality images from molecular structures and do not have software installed locally for structure visualization. Often people do not have a structure viewer, such as RasMol or Chime (or even Java) installed locally but want to visualize a molecule structure interactively. AISMIG (An Interactive Server-side Molecule Image Generator) is a web service that provides a visualization of molecule structures in such cases. AISMIG-URL:

PMG: online generation of high-quality molecular pictures and storyboarded animations

The Protein Movie Generator (PMG) is an online service able to generate high-quality pictures and animations for which one can then define simple storyboards. The PMG can therefore efficiently illustrate concepts such as molecular motion or formation/dissociation of complexes. Emphasis is put on the simplicity of animation generation. Rendering is achieved using Dino coupled to POV-Ray. In order to produce highly informative images, the PMG includes capabilities of using different molecular representations at the same time to highlight particular molecular features. Moreover, sophisticated rendering concepts including scene definition, as well as modeling light and materials are available. The PMG accepts Protein Data Bank (PDB) files as input, which may include series of models or molecular dynamics trajectories and produces images or movies under various formats. PMG can be accessed at http://bioserv.rpbs.jussieu.fr/PMG.html

POLYVIEW-MM: web-based platform for animation and analysis of molecular simulations

Molecular simulations offer important mechanistic and functional clues in studies of proteins and other macromolecules. However, interpreting the results of such simulations increasingly requires tools that can combine information from multiple structural databases and other web resources, and provide highly integrated and versatile analysis tools. Here, we present a new web server that integrates high-quality animation of molecular motion (MM) with structural and functional analysis of macromolecules. The new tool, dubbed POLYVIEW-MM, enables animation of trajectories generated by molecular dynamics and related simulation techniques, as well as visualization of alternative conformers, e.g. obtained as a result of protein structure prediction methods or small molecule docking. To facilitate structural analysis, POLYVIEW-MM combines interactive view and analysis of conformational changes using Jmol and its tailored extensions, publication quality animation using PyMol, and customizable 2D summary plots that provide an overview of MM, e.g. in terms of changes in secondary structure states and relative solvent accessibility of individual residues in proteins. Furthermore, POLYVIEW-MM integrates visualization with various structural annotations, including automated mapping of known inter-action sites from structural homologs, mapping of cavities and ligand binding sites, transmembrane regions and protein domains. URL: http://polyview.cchmc.org/conform.html

Universality in protein residue networks

Residue networks representing 595 nonhomologous proteins are studied. These networks exhibit universal topological characteristics as they belong to the topological class of modular networks formed by several highly interconnected clusters separated by topological cavities. There are some networks which tend to deviate from this universality. These networks represent small-size proteins having less than 200 residues. We explain such differences in terms of the domain structure of these proteins. On the other hand, we find that the topological cavities characterizing proteins residue networks match very well with protein binding sites. We then investigate the effect of the cutoff value used in building the residue network. For small cutoff values, less than 5Å, the cavities found are very large corresponding almost to the whole protein surface. On the contrary, for large cutoff value, more than 10.0 Å, only very large cavities are detected and the networks look very homogeneous. These findings are useful for practical purposes as well as for identifying "protein-like" complex networks. Finally, we show that the main topological class of residue networks is not reproduced by random networks growing according to Erdös-Rényi model or the preferential attachment method of Barabási-Albert. However, the Watts-Strogatz (WS) model reproduces very well the topological class as well as other topological properties of residue network. We propose here a more biologically appealing modification of the WS model to describe residue networks

Charakterisierung von Trix, einem neuen Guaninnukleotid-Austauschfaktor aus Dictyostelium discoideum

The goal of this project was the characterisation of a new guanine nucleotide exchange factor (GEF protein) for Rac GTPases in Dictyostelium discoideum. GEF proteins function as stimulating proteins of Rac GTPases which are of central importance in the regulation of actin-involving processes. Actin is a major component of the cytoskeleton, constituting a dynamic network of filamentous structures which provide the basis for elementary tasks of growth, differentiation, cell movement and cell division. The ameba D. discoideum is a haploid unicellular eukaryote. It serves as a model organism to study basic actin-involving processes in higher organisms. The D. discoideum genome has been fully sequenced recently and comprises a wide range of regulatory components for the actin cytoskeleton. The gene of a novel GEF protein with a coding sequence of 3597 bp was studied in detail. The gene was cloned and the sequence verified. The protein sequence of 1198 amino acids comprises three Calponin homology domains (CH) and one Dbl homology/Pleckstrin homology tandem domain which is a typical sequence feature of GEF proteins. On the basis of this domain architecture the protein was named 'Trix' in short for 'triple Calponin exchange factor'. The CH domains were classified as type 1 and type 1 CH domain (type 3 - type 3 - type 1). This resembles a novel combination of CH domains in a Rho GEF protein. A recombinant fragment carrying the three CH domains was shown to bind and bundle actin filaments which is not explained by the functions that have been described for CH domains so far. In vivo Trix is localised in the area of the actin-rich cell cortex as well as on the membranes of late endocytic vesicles. This suggests a regulatory role for Trix in the assembly or the disassembly of the actin coat that is associated with endocytic vesicles during the late stages of endocytosis. It was shown that Trix is mainly expressed during the vegetative stadium of D. discoideum which would be consistent with the increased endocytosis during growth. An association of Rac GTPases with late endocytic vesicles in D. discoideum was not described so far. Trix displayed no GDP/MANT-GDP exchange activity with the Rac GTPases Rac1a, RacC and RacE, hence the protein could not be allocated to a Rac GTPase signaling pathway. Some of the interactions between exchange factors and their respective Rac GTPases are of a very specific nature. Thus a potential activity of Trix might be directed against a Rac GTPase that has not yet been tested. The activation of Trix might also depend on further uncharacterised regulatory components. Finally, the results of the in vitro assays might differ from the in vivo situation as it has been demonstrated for other Rho GEFs. The Trix gene was disrupted in AX2 wildtype cells by a gene replacement approach. This allowed detailed characterisation of the protein's function in vivo. Trix is not an essential protein. There were no significant differences in the expression of important marker proteins, in phototaxis, chemotaxis, phagocytosis, cytokinesis, and growth of Trix- mutants. The mutant cells showed subtle changes in the organisation of the actin system as well as a slight delay during the developmental cycle. The most severe phenotypic deviation displayed by Trix- mutants consisted in a marked reduction of exocytosis. This provides further evidence for a regulatory function of the protein in exocytosis. The data suggest that Trix plays a role in the organisation of actin-involving processes in D. discoideum, especially in the regulation of the late endocytic cycle. Trix could not be allocated to a specific Rac GTPase signaling pathway and definite structural or dynamic tasks on the basis of the protein’s actin-binding and actin-bundling properties. The subtle phenotypic alterations in Trix- mutants might be due to a general redundancy in the functions of D. discoideum Rho GEF proteins

A remote access CT colonography training system

Computed tomography colonography (CTC) is emerging as an alternative to conventional colonoscopy (CC). However CTC is not yet in widespread use due in part to the lack of suitably trained radiologists. We have developed a novel remote access system to train radiologists for colorectal cancer screening using CTC. To ensure that radiologists can gain the relevant experience without the need for any specialist equipment or software, we opted for designing a system that is accessible via the Internet using a standard browser. The interface lets the user locate and characterise polyps with the help of appropriate tools such as windowing, polyp measurement, zooming and a 3-D view. Each user has an account in order to allow monitoring of their training. They can also run an automatic evaluation of their work based on gold standard information previously gathered from specialists. This thesis also describes an initial implementation exclusively made up of Java Servlets. The evaluation of this system has been discussed in order to determine a better approach. The final system has been developed using a combination of Java Servlets and Applets. This approach offers fast response time to the user-interface. An iteration of lumen tracking using the system takes approximately 45 seconds. This research has yielded an operational system that meets the needs of remote access users

Web-based Stereoscopic Collaboration for Medical Visualization

Medizinische Volumenvisualisierung ist ein wertvolles Werkzeug zur Betrachtung von Volumen- daten in der medizinischen Praxis und Lehre. Eine interaktive, stereoskopische und kollaborative Darstellung in Echtzeit ist notwendig, um die Daten vollständig und im Detail verstehen zu können. Solche Visualisierung von hochauflösenden Daten ist jedoch wegen hoher Hardware- Anforderungen fast nur an speziellen Visualisierungssystemen möglich. Remote-Visualisierung wird verwendet, um solche Visualisierung peripher nutzen zu können. Dies benötigt jedoch fast immer komplexe Software-Deployments, wodurch eine universelle ad-hoc Nutzbarkeit erschwert wird. Aus diesem Sachverhalt ergibt sich folgende Hypothese: Ein hoch performantes Remote- Visualisierungssystem, welches für Stereoskopie und einfache Benutzbarkeit spezialisiert ist, kann für interaktive, stereoskopische und kollaborative medizinische Volumenvisualisierung genutzt werden. Die neueste Literatur über Remote-Visualisierung beschreibt Anwendungen, welche nur reine Webbrowser benötigen. Allerdings wird bei diesen kein besonderer Schwerpunkt auf die perfor- mante Nutzbarkeit von jedem Teilnehmer gesetzt, noch die notwendige Funktion bereitgestellt, um mehrere stereoskopische Präsentationssysteme zu bedienen. Durch die Bekanntheit von Web- browsern, deren einfach Nutzbarkeit und weite Verbreitung hat sich folgende spezifische Frage ergeben: Können wir ein System entwickeln, welches alle Aspekte unterstützt, aber nur einen reinen Webbrowser ohne zusätzliche Software als Client benötigt? Ein Proof of Concept wurde durchgeführt um die Hypothese zu verifizieren. Dazu gehörte eine Prototyp-Entwicklung, deren praktische Anwendung, deren Performanzmessung und -vergleich. Der resultierende Prototyp (CoWebViz) ist eines der ersten Webbrowser basierten Systeme, welches flüssige und interaktive Remote-Visualisierung in Realzeit und ohne zusätzliche Soft- ware ermöglicht. Tests und Vergleiche zeigen, dass der Ansatz eine bessere Performanz hat als andere ähnliche getestete Systeme. Die simultane Nutzung verschiedener stereoskopischer Präsen- tationssysteme mit so einem einfachen Remote-Visualisierungssystem ist zur Zeit einzigartig. Die Nutzung für die normalerweise sehr ressourcen-intensive stereoskopische und kollaborative Anatomieausbildung, gemeinsam mit interkontinentalen Teilnehmern, zeigt die Machbarkeit und den vereinfachenden Charakter des Ansatzes. Die Machbarkeit des Ansatzes wurde auch durch die erfolgreiche Nutzung für andere Anwendungsfälle gezeigt, wie z.B. im Grid-computing und in der Chirurgie