Structural Genomics

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Adam Godzik - One of the best experts on this subject based on the ideXlab platform.

  • Structural Genomics is the largest contributor of novel Structural leverage
    Journal of Structural and Functional Genomics, 2009
    Co-Authors: Rajesh Nair, John K. Everett, Thomas B. Acton, Andras Fiser, Lukasz Jaroszewski, Adam Godzik, Ta Tsen Soong, Andrei Kouranov, Christine A. Orengo
    Abstract:

    The Protein Structural Initiative (PSI) at the US National Institutes of Health (NIH) is funding four large-scale centers for Structural Genomics (SG). These centers systematically target many large families without Structural coverage, as well as very large families with inadequate Structural coverage. Here, we report a few simple metrics that demonstrate how successfully these efforts optimize Structural coverage: while the PSI-2 (2005-now) contributed more than 8% of all structures deposited into the PDB, it contributed over 20% of all novel structures (i.e. structures for protein sequences with no Structural representative in the PDB on the date of deposition). The Structural coverage of the protein universe represented by today’s UniProt (v12.8) has increased linearly from 1992 to 2008; Structural Genomics has contributed significantly to the maintenance of this growth rate. Success in increasing novel leverage (defined in Liu et al. in Nat Biotechnol 25:849–851, 2007) has resulted from systematic targeting of large families. PSI’s per structure contribution to novel leverage was over 4-fold higher than that for non-PSI Structural biology efforts during the past 8 years. If the success of the PSI continues, it may just take another ~15 years to cover most sequences in the current UniProt database.

  • PSI-2: Structural Genomics to cover protein domain family space.
    Structure, 2009
    Co-Authors: Benoit H. Dessailly, Andras Fiser, Lukasz Jaroszewski, Adam Godzik, Burkhard Rost, Andrei Kouranov, R. Nair, J. Eduardo Fajardo, David A. Lee, Christine A. Orengo
    Abstract:

    Summary One major objective of Structural Genomics efforts, including the NIH-funded Protein Structure Initiative (PSI), has been to increase the Structural coverage of protein sequence space. Here, we present the target selection strategy used during the second phase of PSI (PSI-2). This strategy, jointly devised by the bioinformatics groups associated with the PSI-2 large-scale production centers, targets representatives from large, Structurally uncharacterized protein domain families, and from Structurally uncharacterized subfamilies in very large and diverse families with incomplete Structural coverage. These very large families are extremely diverse both Structurally and functionally, and are highly overrepresented in known proteomes. On the basis of several metrics, we then discuss to what extent PSI-2, during its first 3 years, has increased the Structural coverage of genomes, and contributed Structural and functional novelty. Together, the results presented here suggest that PSI-2 is successfully meeting its objectives and provides useful insights into Structural and functional space.

  • the challenge of protein structure determination lessons from Structural Genomics
    Protein Science, 2007
    Co-Authors: Lukasz Slabinski, Lukasz Jaroszewski, Scott A. Lesley, Ana P C Rodrigues, Leszek Rychlewski, Ian A Wilson, Adam Godzik
    Abstract:

    The process of experimental determination of protein structure is marred with a high ratio of failures at many stages. With availability of large quantities of data from high-throughput structure determination in Structural Genomics centers, we can now learn to recognize protein features correlated with failures; thus, we can recognize proteins more likely to succeed and eventually learn how to modify those that are less likely to succeed. Here, we identify several protein features that correlate strongly with successful protein production and crystallization and combine them into a single score that assesses "crystallization feasibility." The formula derived here was tested with a jackknife procedure and validated on independent benchmark sets. The "crystallization feasibility" score described here is being applied to target selection in the Joint Center for Structural Genomics, and is now contributing to increasing the success rate, lowering the costs, and shortening the time for protein structure determination. Analyses of PDB depositions suggest that very similar features also play a role in non-high-throughput structure determination, suggesting that this crystallization feasibility score would also be of significant interest to Structural biology, as well as to molecular and biochemistry laboratories.

  • contribution of electrostatic interactions compactness and quaternary structure to protein thermostability lessons from Structural Genomics of thermotoga maritima
    Journal of Molecular Biology, 2006
    Co-Authors: Marc Robinsonrechavi, Adam Godzik, Andreu Alibes
    Abstract:

    Studies of the Structural basis of protein thermostability have produced a confusing picture. Small sets of proteins have been analyzed from a variety of thermophilic species, suggesting different Structural features as responsible for protein thermostability. Taking advantage of the recent advances in Structural Genomics, we have compiled a relatively large protein structure dataset, which was constructed very carefully and selectively; that is, the dataset contains only experimentally determined structures of proteins from one specific organism, the hyperthermophilic bacterium Thermotoga maritima , and those of close homologs from mesophilic bacteria. In contrast to the conclusions of previous studies, our analyses show that oligomerization order, hydrogen bonds, and secondary structure play minor roles in adaptation to hyperthermophily in bacteria. On the other hand, the data exhibit very significant increases in the density of salt-bridges and in compactness for proteins from T. maritima . The latter effect can be measured by contact order or solvent accessibility, and network analysis shows a specific increase in highly connected residues in this thermophile. These features account for changes in 96% of the protein pairs studied. Our results provide a clear picture of protein thermostability in one species, and a framework for future studies of thermal adaptation.

  • Structural Genomics of thermotoga maritima proteins shows that contact order is a major determinant of protein thermostability
    Structure, 2005
    Co-Authors: Marc Robinsonrechavi, Adam Godzik
    Abstract:

    Summary Despite numerous studies, understanding the Structural basis of protein stability in thermophilic organisms has remained elusive. One of the main reasons is the limited number of thermostable protein structures available for analysis, but also the difficulty in identifying relevant features to compare. Notably, an intuitive feeling of "compactness" of thermostable proteins has eluded quantification. With the unprecedented opportunity to assemble a data set for comparative analyses due to the recent advances in Structural Genomics, we can now revisit this issue and focus on experimentally determined structures of proteins from the hyperthermophilic bacterium Thermotoga maritima . We find that 73% of T. maritima proteins have higher contact order than their mesophilic homologs. Thus, contact order, a Structural feature that was originally introduced to explain differences in folding rates of different protein families, is a significant parameter that can now be correlated with thermostability.

Andrzej Joachimiak - One of the best experts on this subject based on the ideXlab platform.

  • Structural Genomics and the protein data bank
    Journal of Biological Chemistry, 2021
    Co-Authors: Andrzej Joachimiak, Karolina Michalska
    Abstract:

    The field of Structural Genomics arose over the last 3 decades to address a large and rapidly growing divergence between microbial genomic, functional, and Structural data. Several international programs took advantage of the vast genomic sequence information and evaluated the feasibility of structure determination for expanded and newly discovered protein families. As a consequence, Structural Genomics has developed structure-determination pipelines and applied them to a wide range of novel, uncharacterized proteins, often from "microbial dark matter," and later to proteins from human pathogens. Advances were especially needed in protein production and rapid de novo structure solution. The experimental three-dimensional models were promptly made public, facilitating structure determination of other members of the family and helping to understand their molecular and biochemical functions. Improvements in experimental methods and databases resulted in fast progress in molecular and Structural biology. The Protein Data Bank structure repository played a central role in the coordination of Structural Genomics efforts and the Structural biology community as a whole. It facilitated development of standards and validation tools essential for maintaining high quality of deposited Structural data.

  • high throughput crystallography for Structural Genomics
    Current Opinion in Structural Biology, 2009
    Co-Authors: Andrzej Joachimiak
    Abstract:

    Protein X-ray crystallography recently celebrated its 50th anniversary. The structures of myoglobin and hemoglobin determined by Kendrew and Perutz provided the first glimpses into the complex protein architecture and chemistry. Since then, the field of Structural molecular biology has experienced extraordinary progress and now more than 55 000 protein structures have been deposited into the Protein Data Bank. In the past decade many advances in macromolecular crystallography have been driven by world-wide Structural Genomics efforts. This was made possible because of third-generation synchrotron sources, structure phasing approaches using anomalous signal, and cryo-crystallography. Complementary progress in molecular biology, proteomics, hardware and software for crystallographic data collection, structure determination and refinement, computer science, databases, robotics and automation improved and accelerated many processes. These advancements provide the robust foundation for Structural molecular biology and assure strong contribution to science in the future. In this report we focus mainly on reviewing Structural Genomics high-throughput X-ray crystallography technologies and their impact.

  • Automation of protein purification for Structural Genomics.
    Journal of structural and functional genomics, 2004
    Co-Authors: Youngchang Kim, Irina Dementieva, Min Zhou, Lour Lezondra, Pearl Quartey, Grazyna Joachimiak, Olga Korolev, Andrzej Joachimiak
    Abstract:

    A critical issue in Structural Genomics, and in Structural biology in general, is the availability of high-quality samples. The additional challenge in Structural Genomics is the need to produce high numbers of proteins with low sequence similarities and poorly characterized or unknown properties. 'Structural-biology-grade' proteins must be generated in a quantity and quality suitable for structure determination experiments using X-ray crystallography or nuclear magnetic resonance (NMR). The choice of protein purification and handling procedures plays a critical role in obtaining high-quality protein samples. The purification procedure must yield a homogeneous protein and must be highly reproducible in order to supply milligram quantities of protein and/or its derivative containing marker atom(s). At the Midwest Center for Structural Genomics we have developed protocols for high-throughput protein purification. These protocols have been implemented on AKTA EXPLORER 3D and AKTA FPLC 3D workstations capable of performing multidimensional chromatography. The automated chromatography has been successfully applied to many soluble proteins of microbial origin. Various MCSG purification strategies, their implementation, and their success rates are discussed in this paper.

Peter J Myler - One of the best experts on this subject based on the ideXlab platform.

  • Structural Genomics of infectious disease drug targets the ssgcid
    Acta Crystallographica Section F-structural Biology and Crystallization Communications, 2011
    Co-Authors: Robin Stacy, Darren W Begley, Bart L Staker, Wesley C Van Voorhis, Lance J Stewart, Isabelle Phan, Gabriele Varani, Garry W Buchko, Peter J Myler
    Abstract:

    The Seattle Structural Genomics Center for Infectious Disease (SSGCID) is a consortium of researchers at Seattle BioMed, Emerald BioStructures, the University of Washington and Pacific Northwest National Laboratory that was established to apply Structural Genomics approaches to drug targets from infectious disease organisms. The SSGCID is currently funded over a five-year period by the National Institute of Allergy and Infectious Diseases (NIAID) to determine the three-dimensional structures of 400 proteins from a variety of Category A, B and C pathogens. Target selection engages the infectious disease research and drug-therapy communities to identify drug targets, essential enzymes, virulence factors and vaccine candidates of biomedical relevance to combat infectious diseases. The protein-expression systems, purified proteins, ligand screens and three-dimensional structures produced by SSGCID con­stitute a valuable resource for drug-discovery research, all of which is made freely available to the greater scientific community. This issue of Acta Crystallographica Section F, entirely devoted to the work of the SSGCID, covers the details of the high-throughput pipeline and presents a series of structures from a broad array of pathogenic organisms. Here, a background is provided on the Structural Genomics of infectious disease, the essential components of the SSGCID pipeline are discussed and a survey of progress to date is presented.

  • SAD phasing using iodide ions in a high-throughput Structural Genomics environment
    Journal of Structural and Functional Genomics, 2011
    Co-Authors: Jan Abendroth, Bart L Staker, Peter J Myler, Lance J Stewart, Anna S. Gardberg, John I. Robinson, Jeff S. Christensen, Thomas E Edwards
    Abstract:

    The Seattle Structural Genomics Center for Infectious Disease (SSGCID) focuses on the structure elucidation of potential drug targets from class A, B, and C infectious disease organisms. Many SSGCID targets are selected because they have homologs in other organisms that are validated drug targets with known structures. Thus, many SSGCID targets are expected to be solved by molecular replacement (MR), and reflective of this, all proteins are expressed in native form. However, many community request targets do not have homologs with known structures and not all internally selected targets readily solve by MR, necessitating experimental phase determination. We have adopted the use of iodide ion soaks and single wavelength anomalous dispersion (SAD) experiments as our primary method for de novo phasing. This method uses existing native crystals and in house data collection, resulting in rapid, low cost structure determination. Iodide ions are non-toxic and soluble at molar concentrations, facilitating binding at numerous hydrophobic or positively charged sites. We have used this technique across a wide range of crystallization conditions with successful structure determination in 16 of 17 cases within the first year of use (94% success rate). Here we present a general overview of this method as well as several examples including SAD phasing of proteins with novel folds and the combined use of SAD and MR for targets with weak MR solutions. These cases highlight the straightforward and powerful method of iodide ion SAD phasing in a high-throughput Structural Genomics environment.

  • fragment screening of infectious disease targets in a Structural Genomics environment
    Methods in Enzymology, 2011
    Co-Authors: Darren W Begley, Douglas R Davies, Robert C Hartley, Thomas E Edwards, Bart L Staker, Wesley C Van Voorhis, Peter J Myler, Lance J Stewart
    Abstract:

    Abstract Structural Genomics efforts have traditionally focused on generating single protein structures of unique and diverse targets. However, a lone structure for a given target is often insufficient to firmly assign function or to drive drug discovery. As part of the Seattle Structural Genomics Center for Infectious Disease (SSGCID), we seek to expand the focus of Structural Genomics by elucidating ensembles of structures that examine small molecule–protein interactions for selected infectious disease targets. In this chapter, we discuss two applications for small molecule libraries in Structural Genomics: unbiased fragment screening, to provide inspiration for lead development, and targeted, knowledge-based screening, to confirm or correct the functional annotation of a given gene product. This shift in emphasis results in a Structural Genomics effort that is more engaged with the infectious disease research community, and one that produces structures of greater utility to researchers interested in both protein function and inhibitor development. We also describe specific methods for conducting high-throughput fragment screening in a Structural Genomics context by X-ray crystallography.

  • the role of medical Structural Genomics in discovering new drugs for infectious diseases
    PLOS Computational Biology, 2009
    Co-Authors: Wesley C Van Voorhis, Peter J Myler, Wim G J Hol, Lance Stewart
    Abstract:

    Whether we think of Alzheimer's disease, microbial infection, or any other modern-day disease, new medicines are urgently needed. The number of new drugs registered since the advent of Genomics, however, has not lived up to expectations. One recent review revealed that over 70 high-throughput biochemical screens against genetically validated drug targets in bacteria failed to yield a single candidate that could be tested in the clinic [1]. The reasons for the failure of high-throughput biochemical screens are not completely clear, but it could reflect the limited diversity of chemical libraries used and/or the absence of Structural information for many of the targets. Indeed, structure-based drug design is playing a growing role in modern drug discovery, with numerous approved drugs tracing their origins, at least in part, to the use of Structural information from X-ray crystallography or nuclear magnetic resonance (NMR) analysis of protein targets and their ligand-bound complexes. Although it is beyond the scope of this brief overview to present a comprehensive list of structures that have led to useful drugs, Table 1 lists some examples in which protein structure information has provided insights to the design and development of new therapeutic entities. These cases include both novel drug design based on native and ligand-bound structures and optimization of inhibitors based on the binding mode revealed by the structures of inhibitor–target complexes. These approaches have allowed increased affinity for the target and/or improvement of pharmacological properties while maintaining target affinity. Table 1 Examples of how target protein structure can assist drug discovery and development. Source Target Protein Approach Reference(s) HIV gp41 Structure led to strategies that target viral entry. [43]–[45] HIV Protease Protease–inhibitor complexes allowed lead optimization. [46]–[52] HIV Reverse transcriptase Non-nucleoside inhibitor complexes led to drug design that targets pockets outside the enzyme's active site. [53]–[55] Influenza virus Neuraminidase Complex with a transition state analog led to inhalable and orally active neuraminidase inhibitors. [56]–[59] Rhinovirus Coat protein Small fatty acid molecules bound in hydrophobic pocket led to new strategies of antiviral drug design. [60] Vibrio Cholera toxin Five receptor-binding sites provided inspiration for design of novel multivalent inhibitors. [61] Bacteria Peptide deformylase Protein–inhibitor complexes led to macrocyclic compounds with improved potency, selectivity and metabolic stability. [62] Trypanosoma GAPDH Novel adenosine analogs showed enhanced selectivity towards the parasite target versus human protein. [63],[64] Human Cyclophilin and calcineurin A ternary complex with cyclosporine A led to insights into its immunosuppressive activity. [65] Human Renin The ligand-bound structure allowed design and improvement of orally active non-peptide inhibitors to regulate blood pressure. [66] Human Coagulation factor Xa Structure-based design led to improved pharmacological anticoagulant properties in a primate model. [67] Human Adenosine deaminase Optimization of a non-nucleoside inhibitor led to an orally active anti-inflammatory compound in a rat model. [68] Human Kinases Structures of kinases provided a basis to improve and design new therapeutics for various human diseases including cancer. [69] Open in a separate window With the increasing availability of complete human and pathogen genome sequences and the substantial progress in structure determination methods, it is no surprise that the field of “Structural Genomics” has emerged recently. Its aim is to solve as many useful protein structures as possible from the entire genome of a single organism or group of related organisms. Over the past ten years, over 20 Structural Genomics initiatives have begun around the world (Table 2). The impact of these efforts on Structural biology has been substantial, both in the sheer number of new structures and, perhaps even more importantly, in the development of new methodologies, especially the use of robotics and informatics to generate and capture data in a systematic way [2]. Over the next five years, thousands of new protein structures, many bound to their ligands, will be elucidated; laying the groundwork for structure-based design and development of new and improved chemotherapeutic agents against pathogen proteins. Here, we will focus on the intersection of Structural biology with chemistry and biology—a field called “medical Structural Genomics”—particularly on how the structures of medically relevant drug targets in pathogens can serve as a starting point for inhibitor design and drug development. We argue that the pharmaceutical industry should be persuaded to complement the publicly funded Structural Genomics initiatives by making public the Structural coordinates of their drug targets for important infectious disease organisms in a timely fashion and by developing public–private partnerships to provide the maximal synergy between target validation, structure determination, and hit-to-lead development. Table 2 Structural Genomics projects worldwide submitting to the Protein Data Bank. Name URL Target Focus Berkeley Structural Genomics Center (BSGC) http://www.strgen.org/ Near complete coverage of Mycoplasma genome Center for Eukaryotic Structural Genomics (CESG) http://www.uwStructuralGenomics.org/ PSI Center—Eukaryotic bottlenecks, specifically solubility Center for Structural Genomics of Infectious Disease (CSGID) http://csgid.org/csgid/ Medically relevant infectious disease targets Center for Structure of Membrane Proteins (CSMP) http://csmp.ucsf.edu/index.htm PSI Center—Bacterial and human membrane proteins Integrated Center for Structure and Function Innovation (ISFI) htp://techcenter.mbi.ucla.edu/ PSI Center—Protein solubility and crystallization improvement Israel Structural Proteomics Center http://www.weizmann.ac.il/ISPC/ Member of Structural Proteomics in Europe (see below) Joint Center for Structural Genomics (JCSG) http://www.jcsg.org/ PSI Center—High-throughput pipeline development and operation Marseilles Structural Genomics Program http://www.afmb.univ-mrs.fr/rubrique93.html Human health Medical Structural Genomics of Pathogenic Protozoa (MSGPP) http://www.msgpp.org/ Structural and functional Genomics of ten species of pathogenic protozoa Montreal-Kingston Bacterial Structural Genomics Initiative (BSGI) http://euler.bri.nrc.ca/brimsg/bsgi.html ORFs from pathogenic and nonpathogenic bacterial strains Mycobacterium Tuberculosis Structural Genomics Consortium (TBsgc) http://www.doe-mbi.ucla.edu/TB/ Mycobacterium tuberculosis—To understand pathogenesis and for structure-based drug design Mycobacterium Tuberculosis Structural Proteomics Project (X-MTB) http://webclu.bio.wzw.tum.de/binfo/proj/mtb/ 35 Mycobacterium tuberculosis targets to identify five for drug development New York SGX Research Center for Structural Genomics (NYSGXRC) http://www.nysgrc.org/nysgrc/ PSI Center—High-throughput pipeline development and operation Ontario Center for Structural Proteomics (OCSP) http://www.uhnres.utoronto.ca/centres/proteomics/ Enzymatic activity characterization Oxford Protein Production Facility http://www.oppf.ox.ac.uk/OPPF/ Human and pathogen targets of biomedical relevance RIKEN Structural Genomics/Proteomics Initiative http://www.rsgi.riken.jp/rsgi_e/ Protein functional networks Seattle Structural Genomics Center for Infectious Disease (SSGCID) http://www.ssgcid.org/ Medically relevant infectious disease targets Southeast Collaboratory for Structural Genomics http://www.secsg.org/ High-throughput eukaryotic genome-scan methods development Structural Genomics of Pathogenic Protozoa http://www.sgpp.org/ PSI Center - Three-dimensional structures of proteins from four major pathogenic protozoa Structural Proteomics in Europe (SPINE) http://www.spineurope.org/ Structures of medically relevant proteins and protein complexes Structural Proteomics in Europe 2-Complexes (SPINE2 - Complexes) http://www.spine2.eu/SPINE2/ Structures of protein complexes from medically relevant signaling pathways Structural Genomics Consortium http://www.thesgc.org/ Medically relevant human and pathogen proteins Structure 2 Function Project http://s2f.umbi.umd.edu/ Poorly characterized and hypothetical protein targets The Accelerated Technologies Center for Gene to 3D Structure http://atcg3d.org/default.aspx PSI Center—Technologies development of X-ray source, synthetic gene design, and microfluidic crystallization The Midwest Center for Structural Genomics (MCSG) http://www.mcsg.anl.gov/ PSI Center—High-throughput methods development and operation The Northeast Structural Genomics Consortium (NESG) http://www.nesg.org/ PSI Center—Protein domains, network families, biomedical relevance Open in a separate window Note: Some centers with fewer than ten released structures in the PDB (www.rcsb.org/pdb/) are not shown.

  • the seattle Structural Genomics center for infectious disease ssgcid
    Infectious disorders drug targets, 2009
    Co-Authors: Peter J Myler, Bart L Staker, Wesley C Van Voorhis, Robin Stacy, Gabriele Varani, L Stewart, Garry W Buchko
    Abstract:

    The NIAID-funded Seattle Structural Genomics Center for Infectious Disease (SSGCID) is a consortium established to apply Structural Genomics approaches to potential drug targets from NIAID priority organisms for biodefense and emerging and re-emerging diseases. The mission of the SSGCID is to determine ~400 protein structures over five years ending in 2012. In order to maximize biomedical impact, ligand-based drug-lead discovery campaigns will be pursued for a small number of high-impact targets. Here we review the centers target selection processes, which include pro-active engagement of the infectious disease research and drug therapy communities to identify drug targets, essential enzymes, virulence factors and vaccine candidates of biomedical relevance to combat infectious diseases. This is followed by a brief overview of the SSGCID structure determination pipeline and ligand screening methodology. Finally, specifics of our resources available to the scientific community are presented. Physical materials and data produced by SSGCID will be made available to the scientific community, with the aim that they will provide essential groundwork benefiting future research and drug discovery.

Stephen K Burley - One of the best experts on this subject based on the ideXlab platform.

  • protein production from the Structural Genomics perspective achievements and future needs
    Current Opinion in Structural Biology, 2013
    Co-Authors: Steven C. Almo, S Garforth, B Hillerich, J Love, R D Seidel, Stephen K Burley
    Abstract:

    Despite a multitude of recent technical breakthroughs speeding high-resolution Structural analysis of biological macromolecules, production of sufficient quantities of well-behaved, active protein continues to represent the rate-limiting step in many structure determination efforts. These challenges are only amplified when considered in the context of ongoing Structural Genomics efforts, which are now contending with multi-domain eukaryotic proteins, secreted proteins, and ever-larger macromolecular assemblies. Exciting new developments in eukaryotic expression platforms, including insect and mammalian-based systems, promise enhanced opportunities for Structural approaches to some of the most important biological problems. Development and implementation of automated eukaryotic expression techniques promises to significantly improve production of materials for Structural, functional, and biomedical research applications.

  • protein production from the Structural Genomics perspective achievements and future needs
    Current Opinion in Structural Biology, 2013
    Co-Authors: Steven C. Almo, S Garforth, B Hillerich, J Love, R D Seidel, Stephen K Burley
    Abstract:

    Despite a multitude of recent technical breakthroughs speeding high-resolution Structural analysis of biological macromolecules, production of sufficient quantities of well-behaved, active protein continues to represent the rate-limiting step in many structure determination efforts. These challenges are only amplified when considered in the context of ongoing Structural Genomics efforts, which are now contending with multi-domain eukaryotic proteins, secreted proteins, and ever-larger macromolecular assemblies. Exciting new developments in eukaryotic expression platforms, including insect and mammalian-based systems, promise enhanced opportunities for Structural approaches to some of the most important biological problems. Development and implementation of automated eukaryotic expression techniques promises to significantly improve production of materials for Structural, functional, and biomedical research applications.

  • an overview of Structural Genomics
    Nature Structural & Molecular Biology, 2000
    Co-Authors: Stephen K Burley
    Abstract:

    With access to sequences of entire human genomes plus those of various model organisms and many important microbial pathogens, Structural biology is on the verge of a dramatic transformation. Our newfound wealth of sequence information will serve as the foundation for an important initiative in Structural Genomics. We are poised to embark on a systematic program of high-throughput X-ray crystallography and NMR spectroscopy aimed at developing a comprehensive view of the protein structure universe. Structural Genomics will yield a large number of experimental protein structures (tens of thousands) and an even larger number of calculated comparative protein structure models (millions). This enormous body of Structural data will be freely available, and promises to accelerate scientific discovery in all areas of biological science, including biodiversity and evolution in natural ecosystems, agricultural plant genetics, breeding of farm and domestic animals, and human health and disease.

  • Structural Genomics: beyond the Human Genome Project
    Nature Genetics, 1999
    Co-Authors: Stephen K Burley, Andrej Sali, Jeffrey B. Bonanno, Steven C. Almo, Mark R Chance, Malcolm Capel, Terry Gaasterland, Dawei Lin, F. William Studier, Subramanyam Swaminathan
    Abstract:

    With access to whole genome sequences for various organisms and imminent completion of the Human Genome Project, the entire process of discovery in molecular and cellular biology is poised to change. Massively parallel measurement strategies promise to revolutionize how we study and ultimately understand the complex biochemical circuitry responsible for controlling normal development, physiologic homeostasis and disease processes. This information explosion is also providing the foundation for an important new initiative in Structural biology. We are about to embark on a program of high-throughput X-ray crystallography aimed at developing a comprehensive mechanistic understanding of normal and abnormal human and microbial physiology at the molecular level. We present the rationale for creation of a Structural Genomics initiative, recount the efforts of ongoing Structural Genomics pilot studies, and detail the lofty goals, technical challenges and pitfalls facing Structural biologists.

Helen M Berman - One of the best experts on this subject based on the ideXlab platform.

  • the protein structure initiative Structural Genomics knowledgebase
    Nucleic Acids Research, 2009
    Co-Authors: Helen M Berman, John D Westbrook, Andrei Y Kouranov, Margaret Gabanyi, Wendy Tao, Raship Shah, Torsten Schwede, Konstantin Arnold, Florian Kiefer, Lorenza Bordoli
    Abstract:

    The Protein Structure Initiative Structural Genomics Knowledgebase (PSI SGKB, http://kb.psi-StructuralGenomics.org) has been created to turn the products of the PSI Structural Genomics effort into knowledge that can be used by the biological research community to understand living systems and disease. This resource provides central access to structures in the Protein Data Bank (PDB), along with functional annotations, associated homology models, worldwide protein target tracking information, available protocols and the potential to obtain DNA materials for many of the targets. It also offers the ability to search all of the Structural and methodological publications and the innovative technologies that were catalyzed by the PSI's high-throughput research efforts. In collaboration with the Nature Publishing Group, the PSI SGKB provides a research library, editorials about new research advances, news and an events calendar to present a broader view of Structural biology and Structural Genomics. By making these resources freely available, the PSI SGKB serves as a bridge to connect the Structural biology and the greater biomedical communities.

  • the rcsb pdb information portal for Structural Genomics
    Nucleic Acids Research, 2006
    Co-Authors: Andrei Y Kouranov, John D Westbrook, Li Chen, Lei Xie, Joanna De La Cruz, Philip E Bourne, Helen M Berman
    Abstract:

    The RCSB Protein Data Bank (PDB) offers online tools, summary reports and target information related to the worldwide Structural Genomics initiatives from its portal at http://sg.pdb.org. There are currently three components to this site: Structural Genomics Initiatives contains information and links on each Structural Genomics site, including progress reports, target lists, target status, targets in the PDB and level of sequence redundancy; Targets provides combined target information, protocols and other data associated with protein structure determination; and Structures offers an assessment of the progress of Structural Genomics based on the functional coverage of the human genome by PDB structures, Structural Genomics targets and homology models. Functional coverage can be examined according to enzyme classification, gene ontology (biological process, cell component and molecular function) and disease.

  • targetdb a target registration database for Structural Genomics projects
    Bioinformatics, 2004
    Co-Authors: Li Chen, Helen M Berman, Rose Oughtred, John D Westbrook
    Abstract:

    Summary: TargetDB is a centralized target registration database that includes protein target data from the NIH Structural Genomics centers and a number of international sites. TargetDB, which is hosted by the Protein Data Bank (RCSB PDB), provides status information on target sequences and tracks their progress through the various stages of protein production and structure determination. A simple search form permits queries based on contributing site, target ID, protein name, sequence, status and other data. The progress of individual targets or entire Structural Genomics projects may be tracked over time, and target data from all contributing centers may also be downloaded in the XML format. Availability: TagetDB is available at http://targetdb.pdb.org/

  • The Protein Data Bank and Structural Genomics.
    Nucleic acids research, 2003
    Co-Authors: John D Westbrook, Zukang Feng, Li Chen, Huanwang Yang, Helen M Berman
    Abstract:

    The Protein Data Bank (PDB; http://www.pdb.org/) continues to be actively involved in various aspects of the informatics of Structural Genomics projects--developing and maintaining the Target Registration Database (TargetDB), organizing data dictionaries that will define the specification for the exchange and deposition of data with the Structural Genomics centers and creating software tools to capture data from standard structure determination applications.

  • The Protein Data Bank and the challenge of Structural Genomics
    Nature Structural Biology, 2000
    Co-Authors: Helen M Berman, Zukang Feng, Philip E Bourne, T. N. Bhat, Gary Gilliland, Helge Weissig, John Westbrook
    Abstract:

    The PDB has created systems for the processing, exchange, query, and distribution of data that will enable many aspects of high throughput Structural Genomics.

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