Research Article

3DM: Systematic analysis of heterogeneous superfamily data to discover protein functionalities

  1. Remko K. Kuipers1,2,
  2. Henk-Jan Joosten2,3,
  3. Willem J. H. van Berkel4,
  4. Nicole G. H. Leferink4,
  5. Erik Rooijen2,
  6. Erik Ittmann2,
  7. Frank van Zimmeren2,
  8. Helge Jochens5,
  9. Uwe Bornscheuer5,
  10. Gert Vriend1,
  11. Vitor A. P. Martins dos Santos6,
  12. Peter J. Schaap2,6,*

Article first published online: 23 MAR 2010

DOI: 10.1002/prot.22725

Issue

Proteins: Structure, Function, and Bioinformatics

Proteins: Structure, Function, and Bioinformatics

Volume 78, Issue 9, pages 2101–2113, July 2010

Additional Information

How to Cite

Kuipers, R. K., Joosten, H.-J., van Berkel, W. J. H., Leferink, N. G. H., Rooijen, E., Ittmann, E., van Zimmeren, F., Jochens, H., Bornscheuer, U., Vriend, G., Martins dos Santos, V. A. P. and Schaap, P. J. (2010), 3DM: Systematic analysis of heterogeneous superfamily data to discover protein functionalities. Proteins, 78: 2101–2113. doi: 10.1002/prot.22725

Author Information

  1. 1

    Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, 6525 GA Nijmegen, The Netherlands

  2. 2

    Laboratory of Microbiology, Wageningen University, 6703 HB Wageningen, The Netherlands

  3. 3

    Bio-Prodict, 6703 HB Wageningen, The Netherlands

  4. 4

    Laboratory of Biochemistry, Wageningen University, 6703 HA Wageningen, The Netherlands

  5. 5

    Department of Biotechnology and Enzyme Catalysis, Institute of Biochemistry, D-17487 Greifswald, Germany

  6. 6

    Laboratory of Systems and Synthetic Biology, Wageningen University, Dreijenplein 10, 6703 HB Wageningen, The Netherlands

*Laboratory of Microbiology, Wageningen University, Dreijenplein 10, 6703 HB Wageningen, The Netherlands

Publication History

  1. Issue published online: 3 MAY 2010
  2. Article first published online: 23 MAR 2010
  3. Accepted manuscript online: 23 MAR 2010 12:00AM EST
  4. Manuscript Accepted: 11 MAR 2010
  5. Manuscript Revised: 19 FEB 2010
  6. Manuscript Received: 8 JAN 2010

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Keywords:

  • superfamily;
  • protein engineering;
  • drug design;
  • sequence analyses;
  • correlated mutations

Abstract

Ten years of experience with molecular class–specific information systems (MCSIS) such as with the hand-curated G protein–coupled receptor database (GPCRDB) or the semiautomatically generated nuclear receptor database has made clear that a wide variety of questions can be answered when protein-related data from many different origins can be flexibly combined. MCSISes revolve around a multiple sequence alignment (MSA) that includes “all” available sequences from the entire superfamily, and it has been shown at many occasions that the quality of these alignments is the most crucial aspect of the MCSIS approach. We describe here a system called 3DM that can automatically build an entire MCSIS. 3DM bases the MSA on a multiple structure alignment, which implies that the availability of a large number of superfamily members with a known three-dimensional structure is a requirement for 3DM to succeed well. Thirteen MCSISes were constructed and placed on the Internet for examination. These systems have been instrumental in a large series of research projects related to enzyme activity or the understanding and engineering of specificity, protein stability engineering, DNA-diagnostics, drug design, and so forth. Proteins 2010. © 2010 Wiley-Liss, Inc.

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