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There are a huge number of genes which are known to be transcribed (as mRNA) and turned into proteins, but we have no real idea as to what these proteins actual

There are a huge number of genes which are known to be transcribed (as mRNA) and turned into proteins, but we have no real idea as to what these proteins actually looks like, or what their function may be, for example [1]. If we knew their final protein structure, it would be much easier to work out what biological processes they may be involved in. Also, taking known protein structures and learning more about how they may interact with other proteins would be extremely useful. For example, a large number of molecular pathways in cancer are fairly well described in a general sense, but lack specific information on the actual reactions. Finally, being able to put it all together in the context of mutated genes (which we can now screen for fairly easily) and being able to determine what impact a mutation may have on the protein (can it still be formed, how will it interact in a pathway?). For example, some mutations break a protein completely, while others may impact "switch" genes, leaving them in a permanently "on" state preventing them for reacting to external signals [2]. This kind of thing is really important in cancer research (and one day treatment), where the function of specific proteins may be the difference between life and death. [1] http://www.genecards.org/cgi-bin/carddisp.pl?gene=C1orf186 http://www.genecards.org/cgi-bin/carddisp.pl?gene=C1orf186 [2] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1891745/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1891745/

tomkinstinch 14y ago
Computational folding is nice, but it's not the only computationally-intensive activity in proteomics. For some proteins with post-transcriptional (ex. alternative splicing) or post-translational modifications (ex. attachment of functional groups, formation of disulfide bridges, proteolytic cleavage) it is difficult or impossible to arrive at the correct folded structures from computation on nucleic acid sequences alone. For such proteins, the structures can be determined experimentally. That means coaxing pure samples of protein to form single crystals and then subjecting the crystals to X-ray diffraction (XRD). Backing out the structural information from the XRD patterns takes serious horsepower (though admittedly not necessarily power with Titan-class interconnects). XRD does not give information about the location of hydrogen atoms in the structure though. For that information you need to do neutron diffraction (the de Broglie wavelength of the neutrons is short). ORNL is actually one of the few places that do neutron diffraction. The OP could connect with some of the neutron folks there and assist them with their research. If not for proteins, maybe for superconductors. I had a chance to run some Monte Carlo code on some of the machines at ORNL as part of a supercomputing workshop there during the reign of Jaguar. It was an amazing experience. Enjoy it, OP! I hope you get to take a trip there and see all the racks too.
- kayhi 14y ago
  If you need an introduction to the neutron folks at Oak Ridge, let me know.
  - Xcelerate 14y ago
    I'll actually be visiting there early February for an experiment. I believe I'm supposed to do some training first. Do you work there?
    - kayhi 14y ago
      I don't, working on a start up instead. Training is standard for those visiting, which can range from 15min to 3hr depending on what you will be doing. If you haven't make sure to leave enough time to complete it before the training office closes.

tomkinstinch 14y ago

Computational folding is nice, but it's not the only computationally-intensive activity in proteomics. For some proteins with post-transcriptional (ex. alternative splicing) or post-translational modifications (ex. attachment of functional groups, formation of disulfide bridges, proteolytic cleavage) it is difficult or impossible to arrive at the correct folded structures from computation on nucleic acid sequences alone. For such proteins, the structures can be determined experimentally. That means coaxing pure samples of protein to form single crystals and then subjecting the crystals to X-ray diffraction (XRD). Backing out the structural information from the XRD patterns takes serious horsepower (though admittedly not necessarily power with Titan-class interconnects). XRD does not give information about the location of hydrogen atoms in the structure though. For that information you need to do neutron diffraction (the de Broglie wavelength of the neutrons is short). ORNL is actually one of the few places that do neutron diffraction. The OP could connect with some of the neutron folks there and assist them with their research. If not for proteins, maybe for superconductors. I had a chance to run some Monte Carlo code on some of the machines at ORNL as part of a supercomputing workshop there during the reign of Jaguar. It was an amazing experience. Enjoy it, OP! I hope you get to take a trip there and see all the racks too.

kayhi 14y ago
If you need an introduction to the neutron folks at Oak Ridge, let me know.
- Xcelerate 14y ago
  I'll actually be visiting there early February for an experiment. I believe I'm supposed to do some training first. Do you work there?
  - kayhi 14y ago
    I don't, working on a start up instead. Training is standard for those visiting, which can range from 15min to 3hr depending on what you will be doing. If you haven't make sure to leave enough time to complete it before the training office closes.