SG in the Spotlight
Structural genomics milestones
As technologies improve and momentum grows, more and more structural genomics centers are hitting structure determination milestones.
The Center for Structural Genomics for Infectious Diseases (CSGID) reports that they have deposited their 100th structure in the Protein Data Bank (PDB) in less than two years. You can read the full press release here. The CSGID applies structural genomics approaches to potential drug targets from NIAID category A, B, and C priority pathogens, with the goal of solving 500 structures over a five-year period. There is a major emphasis placed on the selection of targets with biomedical relevance and potential therapeutic benefits, particularly complexes of the target proteins with small-molecule ligands such as natural substrates, cofactors and drug candidates, for drug discovery purposes. The CSGID, headed by Wayne Anderson at Northwestern University, comprises a consortium of seven institutions (Northwestern University, University of Chicago, J Craig Venter Institute, University of Virginia, Washington University, University College London and University of Toronto) and is funded by NIAID.
The PSI MCSG has also reached a milestone, being the first PSI center to deposit 1000 protein structures to the PDB since its inception in 2000. The MCSG targets proteins from several biomedical and special classes, with a particular focus on characterization of potential novel virulence factors, pathogenic factors, and cases of viral molecular mimicry in pathogenic bacteria uncovered by bioinformatics methods. Read the full press release here. The PSI MCSG, headed by Andrzej Joachimiak at Argonne National Labs, comprises eight institutions (Argonne National Laboratory, Northwestern University, Washington University School of Medicine, European Bioinformatics Institute, University College London, UT Southwestern Medical Center at Dallas, University of Toronto, and University of Virginia) and funded by the NIGMS.
PSI:Biology Center RFAs released
The NIGMS has recently released RFAs to begin building the next phase of the PSI. These are:
The Centers for High-Throughput Structure Determination (RFA-GM-10-005) will have five main functions: i) determination of protein structures utilizing high-throughput pipeline capabilities; ii) development of technology to improve the pipeline and to attack increasingly difficult proteins and complexes of proteins at high-throughput; iii) bioinformatics analysis of potential targets, solved structures, and the creation of models based on solved structures; iv) dissemination of information and materials via the PSI-Materials Repository and PSI-Structural Genomics Knowledgebase; and v) collaborative research with other members of the network to be established through this and the other RFAs and PARs that are part of this initiative.
The Centers for Membrane Protein Structure Determination (RFA-GM-10-006) will focus on the solution of membrane protein structures of high biological interest and on the development of new methods expected to render membrane protein structures more amenable to high-throughput structure determination.
And, the Consortia for High-Throughput-Enabled Structural Biology Partnerships (RFA-GM-10-007) has the primary purpose of ensuring that a broad community of scientists participates in and benefits from high-throughput structural biology. Applications will be solicited from individuals and groups of scientists who are not associated with the above centers and who propose to collaborate with the network as a whole, not a single specific center. These consortia are expected to include functional characterization of proteins primarily outside of the structure determination centers as well as structure determinations within these centers and thus provide a key link between a structure and its biomedical impact.
Letters of intent are due September 9, 2009, and applications are to be received by October 29, 2009. If you have any questions, please contact the PSI Acting Director, Peter Preusch.
Structural Genomics Knowledgebase Portal spotlight: The Protein Model Portal
As discussed in last month's Spotlight, theoretical protein models are increasingly becoming used to enable biomedical research, especially in cases where no experimental structure exists yet. As part of the Structural Genomics Knowledgebase, the Protein Model Portal (PMP) provides centralized access to pre-built computational models created by the four PSI large-scale centers and also publicly available model databases such as ModBase and SWISS-MODEL. The PMP regularly imports information from the various sources in conjunction with UniProtKB releases to create a unified reference system. The PMP can be accessed via sequence or PDB ID query of the Structural Genomics Knowledgebase website, or via advanced query options directly on the Models Portal, and returns a description of the protein, functional, and domain annotation, a visual overlay of the query sequence and the models, information on template structure and alignment, and provides tools for measuring model features such as structure conservation. The Java application AstexViewer allows users to interactively view the 3D model. In the absence of a pre-computed model, users can also request a model to be generated using a set of established tools as well.
If you have any questions, feel free to contact the PMP.
Want to learn more about the PSI Structural Genomics Knowledgebase? Representatives will be available at these upcoming meetings.
Gordon Research Conference: Mechanisms of Cell Signaling
23–28 August 2009
American Society for Cell Biology Annual Meeting
5-9 December 2009
San Diego, California, USA