Protein Structure Analysis – How Far We’ve Come!

The team here at OpenHelix has recently updated our sponsored tutorials on two excellent structural biology resources, the RCSB Protein Data Bank (PBD) and the PSI-Nature Structural Biology Knowledgebase (PSI SBKB). Because the tutorials are sponsored by these resources they are free for anyone to view and download in full. You can access our training materials for the resources at our RCSB PDB landing page, or our PSI SBKB landing page. I’m very happy with both tutorial suites, so please check them out.

As my personal celebration for these releases I have been reading a variety of articles showing the scope of how far our abilities to analyze protein structures have come. The first article is one that Mary pointed me to a while back, which discusses the infancy of bioinformatics, entitled “The Roots of Bioinformatics in Protein Evolution” by RF Doolittle (cited below, as are all articles mentioned). In this wonderful perspective Dr. Doolittle describes a time when DNA sequencing was unimaginable and protein sequencing was laborious, slow, and yet so new that each day was full of excitement as one more amino acid was identified. It is a revealing glimpse at a research era gone by – to quote Doolittle, “Science as an endeavor thrives on obsolescence.” – and mentions the contributions of Margaret Dayhoff, who Mary has blogged about.

The next historical article that I read was entitled “The Early Years of Retroviral Protease Crystal Structures” by M Miller (freely available on PMC). As you can tell from the title, this covers a time more recent than the Doolittle article, when protein crystallization studies were possible. Dr. Miller traces the X-ray crystal studies of retroviral proteases at the NCI-Fredrick in the late 1980′s and early 1990′s, and she describes how chemical synthesis of HIV1-PR was critical to obtaining enough protein for crystallization and how the crystal structure of it (deposited into the PDB archive and therefore freely available for all researchers to study) was invaluable for the design of inhibitors of HIV1-PR as anti-AIDS drugs.

I’ve also be perusing more recent papers that highlight how protein structures can aid biological investigations. These include: “Structure of mammalian AMPK and its regulation by ADP“,  “Bioinformatics analysis of disordered proteins in prokaryotes“, “Crystal structure of inhibitor of κB kinase β” and others. It would also be fun to attend “The 25th Annual Meeting of the Groups Studying the Structures of AIDS-Related Systems and Their Application to Targeted Drug Design” to learn more, but alas I will not be in the area at the time of the meeting. As I’ve posted before, I am a geneticist by education. To me seeing the development of protein studies (through the historical reviews) and the studies currently occurring in the field of structural biology, combined with the amazing offerings available freely through both the RCSB PDB and the PSI SBKB really does feel like an appropriate, and enjoyable, celebration for the completion of our tutorial updates. Let me know what you think about them, when you get a chance! :)

Updated freely available sponsored tutorials; movie, slides, exercises to use:

References:

  • Berman, H. (2000). The Protein Data Bank Nucleic Acids Research, 28 (1), 235-242 DOI: 10.1093/nar/28.1.235
  • Berman, H., Westbrook, J., Gabanyi, M., Tao, W., Shah, R., Kouranov, A., Schwede, T., Arnold, K., Kiefer, F., Bordoli, L., Kopp, J., Podvinec, M., Adams, P., Carter, L., Minor, W., Nair, R., & Baer, J. (2009). The protein structure initiative structural genomics knowledgebase Nucleic Acids Research, 37 (Database) DOI: 10.1093/nar/gkn790
  • Doolittle, R. (2010). The Roots of Bioinformatics in Protein Evolution PLoS Computational Biology, 6 (7) DOI: 10.1371/journal.pcbi.1000875
  • Miller, M. (2010). The early years of retroviral protease crystal structures Biopolymers, 94 (4), 521-529 DOI: 10.1002/bip.21387

One thought on “Protein Structure Analysis – How Far We’ve Come!

  1. Cyndy

    Right after reading this wonderful tribute to the advances in structural biology, I opened up this week’s Science magazine and spotted a relevant article (http://www.ncbi.nlm.nih.gov/pubmed/21415352 – also a nice perspectives to read). This article describes a new drug (omecamtiv mecarbil) for the treatment of heart failure that has a remarkable ability to increase cardiac contractility. This drug’s mechanism of action is novel, and due to its direct interaction and activation of cardiac muscle myosin. Because the crystal structure of the catalytic domain of muscle myosin had been solved, the authors were able to map this new drug onto the structure, and thus propose a precise molecular mechanism. Really exciting and important science made possible by advances in structural biology!

    Great post Jennifer!

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