The Scientific Activist

New Interactive 3D Molecular Images in Scientific Articles

Posted by Nick Anthis on October 19, 2009
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ResearchBlogging.orgLate last week, I received emails from two journals (The Journal of Biological Chemistry (JBC) and PLoS ONE) indicating that they are now incorporating interactive 3D images of molecular structures in their papers. The atomic coordinates of all published biomolecular structures have been available for some time at the Protein Data Bank. However, making sense of something as complex as a protein structure can require quite a bit of analysis. So, scientists go through great pains to represent important features of their structures in 2D images for publication. Ostensibly, this new functionality will save readers time and enhance their understanding by letting them explore these structures, but starting with the important features already highlighted.

After a quick look at these new interactive 3D images, though, I have to admit that I’m finding the experience slightly cumbersome. Still, this is a good idea, and I imagine that the experience will be improved over time. You can check out the first JBC paper incorporating the interactive images here, and a collection of papers in PLos ONE incorporating the images here. Below is the press release on the subject from PLoS ONE:

On October 20th 2009, PLoS ONE will feature an impressive new 3D molecular animation technology on five newly published articles. This represents the start of a new PLoS ONE collection entitled “Structural Biology and Human Health: Medically Relevant Proteins from the SGC” (also known as the ‘Structural Genomics Consortium’).

These peer-reviewed articles, which include some of the research highlights from the SGC, describe new protein structures, including a protein involved in the survival and proliferation of cancer cells, a protein associated with hereditary paraplegia, and a protein involved in degrading foreign compounds and pollutants in the body.

Readers of these enhanced articles will first need to download a free plug-in for their browser but will then be able to click on hyperlinked text within the article to ‘fly’ to the relevant position within the molecule, and to then interact with it at will (by zooming, rotating and exploring). The functionality, whereby the text of an academic article is tightly integrated with an animated and interactive molecular structure, provides an entirely new and enhanced experience with a significant “wow” factor.

‘It’s like directing your own movie to reveal what you want to see,’ says Dr Brian Marsden of the SGC at the University of Oxford. ‘Anyone is now able to look at proteins important for medicine in 3D and move them around as they wish whilst reading about what they are looking at. It’s very intuitive and it should help drug developers in designing new targeted treatments.’

‘At a glance, anyone can now see the proteins for themselves and get all the insight they can by viewing and manipulating the structures in three dimensions whilst reading about what they are seeing,’ says Dr Wen Hwa Lee, Senior Scientist in Research Informatics at the SGC. ‘This is far, far better than having to interpret the results of the 500-year-old technology of static images in printed journals.’

Knowledge of the three-dimensional shape of a protein is crucial in appreciating how it carries out its role in the body. By understanding a protein’s structure in atomic detail, it is possible to understand the effect of a genetic mutation, or to design drugs to inhibit the action of a protein involved in disease. In the past, researchers have been able to determine the structure of proteins using data generated from protein crystals at synchrotrons (large scientific facilities like Diamond in Oxfordshire which generate extremely bright X-ray beams), but until now it has required specialised software to view the structures in detail (and that software does not integrate well with any published literature on the molecule). The result has been that the value of the work is not always apparent to researchers outside this area, including geneticists, pharmaceutical chemists and clinicians, who might benefit from the data in f urthering their own work in understanding human diseases.

The interactive viewer, called iSee (developed in collaboration with Ruben Abagyan and team at MolSoft LLC), helps scientists understand molecules critical to human health more instinctively by allowing them free reign to explore proteins in atomic detail at the same time as reading the peer reviewed academic paper that has been written about that molecule. It is hoped that this functionality will drive the smarter design of drugs, provide insight into crucial mutations responsible for various conditions, and reveal important biochemistry in molecules involved in human disease.

The iSee technology has already proved its worth in accelerating new discoveries. For example, a small molecule drug originally developed at OxfordUniversity has been the main treatment for osteoporosis for decades, but it was not understood how the drug worked. As soon as the drug company, Proctor & Gamble, looked at the protein, known as FDPS, using iSee, they understood immediately how their drug Actonel (also known as risedronate) worked by binding to the protein. The drug molecule fitted precisely in a pocket in the protein revealed in the 3D structure.

‘iSee revealed exactly how Actonel works, something that had evaded researchers for decades,’ says Professor Udo Oppermann from the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, who directed the work to solve the structure of the protein targeted by Actonel. ‘Understanding how any drug works in atomic detail can potentially allow it to be improved.’

The ground-breaking technology underpinning iSee, developed by MolSoft and known as activeICM, allows anyone with a PC or Mac to run and interact with the iSee viewer in web browsers such as Internet Explorer and Firefox (upon installing a plug-in) or to download a stand-alone viewer to run the datapacks independently of a browser.

The SGC at the University of Oxford and its sister nodes at the University of Toronto, Canada, and the Karolinska Institutet, Sweden, are dedicated to finding the structures of human proteins of medical relevance which could be targets for new drugs. iSee forms a key part of the SGC’s ‘open access’ science philosophy to make its data freely available to all and to provide it in a format which maximises the accessibility and understanding for researchers in all fields. The SGC has over 500 datapacks already available over the web and plan to publish a significant number of academic papers incorporating these datapacks over the next four years with PLoS ONE.

Kumar, P., Vahedi-Faridi, A., Saenger, W., Merino, E., Lopez de Castro, J., Uchanska-Ziegler, B., & Ziegler, A. (2009). Structural Basis for T Cell Alloreactivity among Three HLA-B14 and HLA-B27 Antigens Journal of Biological Chemistry, 284 (43), 29784-29797 DOI: 10.1074/jbc.M109.038497

Raush, E., Totrov, M., Marsden, B., & Abagyan, R. (2009). A New Method for Publishing Three-Dimensional Content PLoS ONE, 4 (10) DOI: 10.1371/journal.pone.0007394

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Comments

  1. #1 CrystalCowboy
    October 20, 2009

    The iSee technology has already proved its worth in accelerating new discoveries. For example, a small molecule drug originally developed at Oxford University has been the main treatment for osteoporosis for decades, but it was not understood how the drug worked. As soon as the drug company, Proctor & Gamble, looked at the protein, known as FDPS, using iSee, they understood immediately how their drug Actonel (also known as risedronate) worked by binding to the protein. The drug molecule fitted precisely in a pocket in the protein revealed in the 3D structure.

    If I read that correctly, the availability of the protein structure, presumably solved by crystallography, made this fresh insight possible. The fact that they used iSee rather than any of the other 3D molecular visualization programs which have been available for decades seems irrelevant, and therefore using this to tout iSee as having some special capability is misleading. Indeed, according to the Protein Data Bank, the coordinates for FDPS (more precisely known as histone-binding protein RBBP4, PDB ID code 3gfc) were only deposited earlier this year.

  2. #2 Nick Anthis
    October 20, 2009

    I think that your assessment is correct. Like most press releases, it looks like this one is a bit overblown.

  3. #3 Dale B. Ritter, B.A.
    October 23, 2009

    Interactive 3D molecular models, as suggested, may demand a good deal of analysis assisted by ultrasensitive instruments. The specific mechanisms of biomolecular interaction have function solutions in terms of elemental atomic identities, environment, and photon gain which may be calculated by relative quantum physics as well. That all depends on the atomic topological function used to model the example, and advances research in proportion to the data density of the wavefunction model.

    Recent advancements in quantum science have produced the picoyoctometric, 3D, interactive video atomic model imaging function, in terms of chronons and spacons for exact, quantized, relativistic animation. This format returns clear numerical data for a full spectrum of variables. The atom’s RQT (relative quantum topological) data point imaging function is built by combination of the relativistic Einstein-Lorenz transform functions for time, mass, and energy with the workon quantized electromagnetic wave equations for frequency and wavelength.

    The atom labeled psi (Z) pulsates at the frequency {Nhu=e/h} by cycles of {e=m(c^2)} transformation of nuclear surface mass to forcons with joule values, followed by nuclear force absorption. This radiation process is limited only by spacetime boundaries of {Gravity-Time}, where gravity is the force binding space to psi, forming the GT integral atomic wavefunction. The expression is defined as the series expansion differential of nuclear output rates with quantum symmetry numbers assigned along the progression to give topology to the solutions.

    Next, the correlation function for the manifold of internal heat capacity energy particle 3D functions is extracted by rearranging the total internal momentum function to the photon gain rule and integrating it for GT limits. This produces a series of 26 topological waveparticle functions of the five classes; {+Positron, Workon, Thermon, -Electromagneton, Magnemedon}, each the 3D data image of a type of energy intermedon of the 5/2 kT J internal energy cloud, accounting for all of them.

    Those 26 energy data values intersect the sizes of the fundamental physical constants: h, h-bar, delta, nuclear magneton, beta magneton, k (series). They quantize nuclear dynamics by acting as fulcrum particles. The result is the picoyoctometric, 3D, interactive video atomic model data point imaging function, responsive to keyboard input of virtual photon gain events by relativistic, quantized shifts of electron, force, and energy field states and positions.

    Images of the h-bar magnetic energy waveparticle of ~175 picoyoctometers are available online at http://www.symmecon.com with the complete RQT atomic modeling manual titled The Crystalon Door, copyright TXu1-266-788. TCD conforms to the unopposed motion of disclosure in U.S. District (NM) Court of 04/02/2001 titled The Solution to the Equation of Schrodinger.

  4. #4 Tyler
    October 24, 2009

    CrystalCowboy – I think the merit here is that iSee ‘walks you through’ the structure. It also spares you from doing the hard work of retrieving the PDB, then painfully recreating the figures from a flat paper, just to check it in 3D yourself.

    Also, you’ve mentioned ‘any of the other 3D molecular visualization programs which have been available for decades’, but how many can really easily use them? I actually know several med chems who can only operate in 2D!! (how many chemistry drawing programs can draw 3D? Why do chemists keep on using the dashed and full wedges to show bonds ‘coming in or out of the plane’ even in computers?)

    You mentioned “Indeed, according to the Protein Data Bank, the coordinates for FDPS (more precisely known as histone-binding protein RBBP4, PDB ID code 3gfc) were only deposited earlier this year.”

    I also like to check the facts and have found that FDPS has indeed been deposited in *2005* (!). Simply type ‘FDPS’ into http://www.rcsb.org (one of the official PDB repositories) and you’ll find that FDPS (pdb code 1YQ7) has been deposited in Feb.2005. And it is called ‘farnesyl diphosphate synthase’ and has nothing to do with RBBP4.

  5. #5 jeffdavisrock
    May 7, 2012

    This work is good i like it and so do others,actually we are also under the same business that is 3D Animation Services
    url:http://cattechnologies.com/3DDevelopment.aspx
    please do have a look.