Information servers, present and future

Mainframes, corporate and central servers are becoming information servers. The requirement for more powerful information servers is the best opportunity to exploit the potential of parallelism. ICL recognized the opportunity of the 'knowledge spectrum' namely to convert raw data into information and then into high grade knowledge. Parallel Processing and Data Management Its response to this and to the underlying search problems was to introduce the CAFS retrieval engine. The CAFS product demonstrates that it is possible to move functionality within an established architecture, introduce a different technology mix and exploit parallelism to achieve radically new levels of performance. CAFS also demonstrates the benefit of achieving this transparently behind existing interfaces. ICL is now working with Bull and Siemens to develop the information servers of the future by exploiting new technologies as available. The objective of the joint Esprit II European Declarative System project is to develop a smoothly scalable, highly parallel computer system, EDS. EDS will in the main be an SQL server and an information server. It will support the many data-intensive applications which the companies foresee; it will also support application-intensive and logic-intensive systems.

Prediction of global and local model quality in CASP8 using the ModFOLD server

The development of effective methods for predicting the quality of three-dimensional (3D) models is fundamentally important for the success of tertiary structure (TS) prediction strategies. Since CASP7, the Quality Assessment (QA) category has existed to gauge the ability of various model quality assessment programs (MQAPs) at predicting the relative quality of individual 3D models. For the CASP8 experiment, automated predictions were submitted in the QA category using two methods from the ModFOLD server-ModFOLD version 1.1 and ModFOLDclust. ModFOLD version 1.1 is a single-model machine learning based method, which was used for automated predictions of global model quality (QMODE1). ModFOLDclust is a simple clustering based method, which was used for automated predictions of both global and local quality (QMODE2). In addition, manual predictions of model quality were made using ModFOLD version 2.0-an experimental method that combines the scores from ModFOLDclust and ModFOLD v1.1. Predictions from the ModFOLDclust method were the most successful of the three in terms of the global model quality, whilst the ModFOLD v1.1 method was comparable in performance to other single-model based methods. In addition, the ModFOLDclust method performed well at predicting the per-residue, or local, model quality scores. Predictions of the per-residue errors in our own 3D models, selected using the ModFOLD v2.0 method, were also the most accurate compared with those from other methods. All of the MQAPs described are publicly accessible via the ModFOLD server at: http://www.reading.ac.uk/bioinf/ModFOLD/. The methods are also freely available to download from: http://www.reading.ac.uk/bioinf/downloads/.

The ModFOLD server for the quality assessment of protein structural models

The reliable assessment of the quality of protein structural models is fundamental to the progress of structural bioinformatics. The ModFOLD server provides access to two accurate techniques for the global and local prediction of the quality of 3D models of proteins. Firstly ModFOLD, which is a fast Model Quality Assessment Program (MQAP) used for the global assessment of either single or multiple models. Secondly ModFOLDclust, which is a more intensive method that carries out clustering of multiple models and provides per-residue local quality assessment.

The DISOPRED server for the prediction of protein disorder

Dynamically disordered regions appear to be relatively abundant in eukaryotic proteomes. The DISOPRED server allows users to submit a protein sequence, and returns a probability estimate of each residue in the sequence being disordered. The results are sent in both plain text and graphical formats, and the server can also supply predictions of secondary structure to provide further structural information.

The PSIPRED protein structure prediction server

The PSIPRED protein structure prediction server allows users to submit a protein sequence, perform a prediction of their choice and receive the results of the prediction both textually via e-mail and graphically via the web. The user may select one of three prediction methods to apply to their sequence: PSIPRED, a highly accurate secondary structure prediction method; MEMSAT 2, a new version of a widely used transmembrane topology prediction method; or GenTHREADER, a sequence profile based fold recognition method.

The ModFOLD4 server for the quality assessment of 3D protein models

Once you have generated a 3D model of a protein, how do you know whether it bears any resemblance to the actual structure? To determine the usefulness of 3D models of proteins, they must be assessed in terms of their quality by methods that predict their similarity to the native structure. The ModFOLD4 server is the latest version of our leading independent server for the estimation of both the global and local (per-residue) quality of 3D protein models. The server produces both machine readable and graphical output, providing users with intuitive visual reports on the quality of predicted protein tertiary structures. The ModFOLD4 server is freely available to all at: http://www.reading.ac.uk/bioinf/ModFOLD/.

The FunFOLD2 server for the prediction of protein-ligand interactions

The FunFOLD2 server is a new independent server that integrates our novel protein–ligand binding site and quality assessment protocols for the prediction of protein function (FN) from sequence via structure. Our guiding principles were, first, to provide a simple unified resource to make our function prediction software easily accessible to all via a simple web interface and, second, to produce integrated output for predictions that can be easily interpreted. The server provides a clean web interface so that results can be viewed on a single page and interpreted by non-experts at a glance. The output for the prediction is an image of the top predicted tertiary structure annotated to indicate putative ligand-binding site residues. The results page also includes a list of the most likely binding site residues and the types of predicted ligands and their frequencies in similar structures. The protein–ligand interactions can also be interactively visualized in 3D using the Jmol plug-in. The raw machine readable data are provided for developers, which comply with the Critical Assessment of Techniques for Protein Structure Prediction data standards for FN predictions. The FunFOLD2 webserver is freely available to all at the following web site: http://www.reading.ac.uk/bioinf/FunFOLD/FunFOLD_form_2_0.html.

Assessing the quality of modelled 3D protein structures using the ModFOLD server

Model quality assessment programs (MQAPs) aim to assess the quality of modelled 3D protein structures. The provision of quality scores, describing both global and local (per-residue) accuracy are extremely important, as without quality scores we are unable to determine the usefulness of a 3D model for further computational and experimental wet lab studies.Here, we briefly discuss protein tertiary structure prediction, along with the biennial Critical Assessment of Techniques for Protein Structure Prediction (CASP) competition and their key role in driving the field of protein model quality assessment methods (MQAPs). We also briefly discuss the top MQAPs from the previous CASP competitions. Additionally, we describe our downloadable and webserver-based model quality assessment methods: ModFOLD3, ModFOLDclust, ModFOLDclustQ, ModFOLDclust2, and IntFOLD-QA. We provide a practical step-by-step guide on using our downloadable and webserver-based tools and include examples of their application for improving tertiary structure prediction, ligand binding site residue prediction, and oligomer predictions.

IntFOLD: an integrated server for modelling protein structures and functions from amino acid sequences

IntFOLD is an independent web server that integrates our leading methods for structure and function prediction. The server provides a simple unified interface that aims to make complex protein modelling data more accessible to life scientists. The server web interface is designed to be intuitive and integrates a complex set of quantitative data, so that 3D modelling results can be viewed on a single page and interpreted by non-expert modellers at a glance. The only required input to the server is an amino acid sequence for the target protein. Here we describe major performance and user interface updates to the server, which comprises an integrated pipeline of methods for: tertiary structure prediction, global and local 3D model quality assessment, disorder prediction, structural domain prediction, function prediction and modelling of protein-ligand interactions. The server has been independently validated during numerous CASP (Critical Assessment of Techniques for Protein Structure Prediction) experiments, as well as being continuously evaluated by the CAMEO (Continuous Automated Model Evaluation) project. The IntFOLD server is available at: http://www.reading.ac.uk/bioinf/IntFOLD/

Grid Remote Execution (G-Rex) of Climate Models

G-Rex is light-weight Java middleware that allows scientific applications deployed on remote computer systems to be launched and controlled as if they are running on the user's own computer. G-Rex is particularly suited to ocean and climate modelling applications because output from the model is transferred back to the user while the run is in progress, which prevents the accumulation of large amounts of data on the remote cluster. The G-Rex server is a RESTful Web application that runs inside a servlet container on the remote system, and the client component is a Java command line program that can easily be incorporated into existing scientific work-flow scripts. The NEMO and POLCOMS ocean models have been deployed as G-Rex services in the NERC Cluster Grid, and G-Rex is the core grid middleware in the GCEP and GCOMS e-science projects.

Running Climate Models On The NERC Cluster Grid Using G-Rex

Compute grids are used widely in many areas of environmental science, but there has been limited uptake of grid computing by the climate modelling community, partly because the characteristics of many climate models make them difficult to use with popular grid middleware systems. In particular, climate models usually produce large volumes of output data, and running them usually involves complicated workflows implemented as shell scripts. For example, NEMO (Smith et al. 2008) is a state-of-the-art ocean model that is used currently for operational ocean forecasting in France, and will soon be used in the UK for both ocean forecasting and climate modelling. On a typical modern cluster, a particular one year global ocean simulation at 1-degree resolution takes about three hours when running on 40 processors, and produces roughly 20 GB of output as 50000 separate files. 50-year simulations are common, during which the model is resubmitted as a new job after each year. Running NEMO relies on a set of complicated shell scripts and command utilities for data pre-processing and post-processing prior to job resubmission. Grid Remote Execution (G-Rex) is a pure Java grid middleware system that allows scientific applications to be deployed as Web services on remote computer systems, and then launched and controlled as if they are running on the user's own computer. Although G-Rex is general purpose middleware it has two key features that make it particularly suitable for remote execution of climate models: (1) Output from the model is transferred back to the user while the run is in progress to prevent it from accumulating on the remote system and to allow the user to monitor the model; (2) The client component is a command-line program that can easily be incorporated into existing model work-flow scripts. G-Rex has a REST (Fielding, 2000) architectural style, which allows client programs to be very simple and lightweight and allows users to interact with model runs using only a basic HTTP client (such as a Web browser or the curl utility) if they wish. This design also allows for new client interfaces to be developed in other programming languages with relatively little effort. The G-Rex server is a standard Web application that runs inside a servlet container such as Apache Tomcat and is therefore easy to install and maintain by system administrators. G-Rex is employed as the middleware for the NERC1 Cluster Grid, a small grid of HPC2 clusters belonging to collaborating NERC research institutes. Currently the NEMO (Smith et al. 2008) and POLCOMS (Holt et al, 2008) ocean models are installed, and there are plans to install the Hadley Centre’s HadCM3 model for use in the decadal climate prediction project GCEP (Haines et al., 2008). The science projects involving NEMO on the Grid have a particular focus on data assimilation (Smith et al. 2008), a technique that involves constraining model simulations with observations. The POLCOMS model will play an important part in the GCOMS project (Holt et al, 2008), which aims to simulate the world’s coastal oceans. A typical use of G-Rex by a scientist to run a climate model on the NERC Cluster Grid proceeds as follows :(1) The scientist prepares input files on his or her local machine. (2) Using information provided by the Grid’s Ganglia3 monitoring system, the scientist selects an appropriate compute resource. (3) The scientist runs the relevant workflow script on his or her local machine. This is unmodified except that calls to run the model (e.g. with “mpirun”) are simply replaced with calls to "GRexRun" (4) The G-Rex middleware automatically handles the uploading of input files to the remote resource, and the downloading of output files back to the user, including their deletion from the remote system, during the run. (5) The scientist monitors the output files, using familiar analysis and visualization tools on his or her own local machine. G-Rex is well suited to climate modelling because it addresses many of the middleware usability issues that have led to limited uptake of grid computing by climate scientists. It is a lightweight, low-impact and easy-to-install solution that is currently designed for use in relatively small grids such as the NERC Cluster Grid. A current topic of research is the use of G-Rex as an easy-to-use front-end to larger-scale Grid resources such as the UK National Grid service.