The Protein Data Bank: Present status and future plans

The Protein Data Bank (PDB) archival database of dimensional structures of biological macromolecules, an international resource facility, contains information on protein, DNA, RNA, virus and carbohydrate structures. While the vast majority of PDB entries represent crystal structures, results from NMR and theoretical modeling strudies also are included. PDB, which in July 1992 contained 957 atomic coordinate entries, currently is experiencing a time of explosive growth. The present deposition rate is ca. 50 structures per month, doubling in less than two years. Responding to the challenge posed by this. rising data flow, over the past 18 months PDB has attracted increased funding to implement important enhancements of the resource. A rapid pre-release of entries pending for input was inaugurated in April 1992, and a substantial fraction of the accumulated backlog of pending entries is now available via FTP and e-mail in prerelease form. Extrapolation of current data rates suggests that by the year 2000 PDB may contain over 25,000 structures. PDB`s plans, to manage this voluminous amount of data, include the development of PDB-AUTHORIN software to allow depositors to do most of the preparation and validation of their own entries, and a comprehensive upgrade of PDB contents to add new data items and convert the current interchange format to the Crystallographic Information File (CIF) standard established by the International Union of Crystallography (IUCr)

Designing Medical Informatics Research and Library--Resource Projects to Increase What Is Learned

Careful study of medical informatics research and library-resource projects is necessary to increase the productivity of the research and development enterprise. Medical informatics research projects can present unique problems with respect to evaluation. It is not always possible to adapt directly the evaluation methods that are commonly employed in the natural and social sciences. Problems in evaluating medical informatics projects may be overcome by formulating system development work in terms of a testable hypothesis; subdividing complex projects into modules, each of which can be developed, tested and evaluated rigorously; and utilizing qualitative studies in situations where more definitive quantitative studies are impractical

A structural annotation resource for the selection of putative target proteins in the malaria parasite

<p>Abstract</p> <p>Background</p> <p>Protein structure plays a pivotal role in elucidating mechanisms of parasite functioning and drug resistance. Moreover, protein structure aids the determination of protein function, which can together with the structure be used to identify novel drug targets in the parasite. However, various structural features in <it>Plasmodium falciparum </it>proteins complicate the experimental determination of protein structures. Limited similarity to proteins in the Protein Data Bank and the shortage of solved protein structures in the malaria parasite necessitate genome-scale structural annotation of <it>P. falciparum </it>proteins. Additionally, the annotation of a range of structural features facilitates the identification of suitable targets for experimental and computational studies.</p> <p>Methods</p> <p>An integrated structural annotation system was developed and applied to <it>P. falciparum</it>, <it>Plasmodium vivax </it>and <it>Plasmodium yoelii</it>. The annotation included searches for sequence similarity, patterns and domains in addition to the following predictions: secondary structure, transmembrane helices, protein disorder, low complexity, coiled-coils and small molecule interactions. Subsequently, candidate proteins for further structural studies were identified based on the annotated structural features.</p> <p>Results</p> <p>The annotation results are accessible through a web interface, enabling users to select groups of proteins which fulfil multiple criteria pertaining to structural and functional features <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. Analysis of features in the <it>P. falciparum </it>proteome showed that protein-interacting proteins contained a higher percentage of predicted disordered residues than non-interacting proteins. Proteins interacting with 10 or more proteins have a disordered content concentrated in the range of 60–100%, while the disorder distribution for proteins having only one interacting partner, was more evenly spread.</p> <p>Conclusion</p> <p>A series of <it>P. falciparum </it>protein targets for experimental structure determination, comparative modelling and <it>in silico </it>docking studies were putatively identified. The system is available for public use, where researchers may identify proteins by querying with multiple physico-chemical, sequence similarity and interaction features.</p

Metabolic reconstruction of sulfur assimilation in the extremophile Acidithiobacillus ferrooxidans based on genome analysis

BACKGROUND: Acidithiobacillus ferrooxidans is a gamma-proteobacterium that lives at pH2 and obtains energy by the oxidation of sulfur and iron. It is used in the biomining industry for the recovery of metals and is one of the causative agents of acid mine drainage. Effective tools for the study of its genetics and physiology are not in widespread use and, despite considerable effort, an understanding of its unusual physiology remains at a rudimentary level. Nearly complete genome sequences of A. ferrooxidans are available from two public sources and we have exploited this information to reconstruct aspects of its sulfur metabolism. RESULTS: Two candidate mechanisms for sulfate uptake from the environment were detected but both belong to large paralogous families of membrane transporters and their identification remains tentative. Prospective genes, pathways and regulatory mechanisms were identified that are likely to be involved in the assimilation of sulfate into cysteine and in the formation of Fe-S centers. Genes and regulatory networks were also uncovered that may link sulfur assimilation with nitrogen fixation, hydrogen utilization and sulfur reduction. Potential pathways were identified for sulfation of extracellular metabolites that may possibly be involved in cellular attachment to pyrite, sulfur and other solid substrates. CONCLUSIONS: A bioinformatic analysis of the genome sequence of A. ferrooxidans has revealed candidate genes, metabolic process and control mechanisms potentially involved in aspects of sulfur metabolism. Metabolic modeling provides an important preliminary step in understanding the unusual physiology of this extremophile especially given the severe difficulties involved in its genetic manipulation and biochemical analysis

Initial sequencing and analysis of the human genome

The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62798/1/409860a0.pd

The Protein Data Bank: Present status and future plans

The Protein Data Bank (PDB) archival database of dimensional structures of biological macromolecules, an international resource facility, contains information on protein, DNA, RNA, virus and carbohydrate structures. While the vast majority of PDB entries represent crystal structures, results from NMR and theoretical modeling strudies also are included. PDB, which in July 1992 contained 957 atomic coordinate entries, currently is experiencing a time of explosive growth. The present deposition rate is ca. 50 structures per month, doubling in less than two years. Responding to the challenge posed by this. rising data flow, over the past 18 months PDB has attracted increased funding to implement important enhancements of the resource. A rapid pre-release of entries pending for input was inaugurated in April 1992, and a substantial fraction of the accumulated backlog of pending entries is now available via FTP and e-mail in prerelease form. Extrapolation of current data rates suggests that by the year 2000 PDB may contain over 25,000 structures. PDB's plans, to manage this voluminous amount of data, include the development of PDB-AUTHORIN software to allow depositors to do most of the preparation and validation of their own entries, and a comprehensive upgrade of PDB contents to add new data items and convert the current interchange format to the Crystallographic Information File (CIF) standard established by the International Union of Crystallography (IUCr)