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Science Forum

  1. 28 Nov '10 18:40
    I am wondering, has any microscopy been developed or is currently being developed that can see features in, say, a protein molecule that are just 0.2nm across (about two carbon atom-widths) while that protein molecule is in liquid water?
    -anyone?

    I know that, using "soft x-ray microscopy", it is possible to see features in a protein molecule while that protein molecule is in its natural state which means it must be in liquid water. But, it is my understanding that the theoretical limit to the smallest features that soft x-ray microscopy can see on a protein molecule is about 1.2nm across and, and correct me if I am wrong, as far as I am aware no X-ray microscope has come close to seeing anything that small.

    I know that electron microscopes cannot do it because no liquid can exist in a vacuum (and the electrons have to travel through a vacuum to the sample in an electron microscope) and optical microscopes cannot do it because the smallest feature that can be seen with light is half a wavelength of that light across.
  2. Standard member sonhouse
    Fast and Curious
    28 Nov '10 20:11
    Originally posted by Andrew Hamilton
    I am wondering, has any microscopy been developed or is currently being developed that can see features in, say, a protein molecule that are just 0.2nm across (about two carbon atom-widths) while that protein molecule is in liquid water?
    -anyone?

    I know that, using "soft x-ray microscopy", it is possible to see features in a protein molecule whi ...[text shortened]... se the smallest feature that can be seen with light is half a wavelength of that light across.
    I think you are dreaming! The best optical scopes can only go down to 200 nm, about a thousand time higher than the resolution you seek. It might be possible to do in in ice in an electron microscope but that is not water. I am thinking of having the protean stuck on the surface of an ice molecule to hold it in place then put that in a vacuum, the ice as close to 0 K as possible so it doesn't sublimate away too fast. But water, like you said, no getta de vacuum with aqua. I work in the semiconductor field on machines like ion implanters, sputtering machines and the like which takes what on Earth passes for a high vacuum, not even close to what's up at 500 km high but good enough to make semiconductors, 5 E-8 torr, using cryo pumps and any bit of liquid water will sure mess up that vacuum. I have had to fix many a water leak in a high vac system, so I know about that for sure. You might have a better chance with ice but that may defeat your purpose.
  3. 28 Nov '10 20:11 / 1 edit
    Originally posted by Andrew Hamilton
    I am wondering, has any microscopy been developed or is currently being developed that can see features in, say, a protein molecule that are just 0.2nm across (about two carbon atom-widths) while that protein molecule is in liquid water?
    -anyone?

    I know that, using "soft x-ray microscopy", it is possible to see features in a protein molecule whi ...[text shortened]... se the smallest feature that can be seen with light is half a wavelength of that light across.
    My understanding is that it is possible to determine the shape of protein molecules but it is not easy nor cheap. The various projects to determine protein shapes via software prediction are partly to help develop custom molecules, but also to try and determine the shape of existing proteins quicker and easier than physical methods.

    If you looked around site like rosetta@home or folding@home you might find out how it is currently done.

    [edit]
    I found this sentence:
    "Currently, millions of dollars are being spent in structural genomics efforts to determine the structures of proteins experimentally using X-ray crystallography and nuclear magnetic resonance (NMR)."

    http://boinc.bakerlab.org/rosetta/rah_about.php#why
  4. 28 Nov '10 23:12
    Originally posted by Andrew Hamilton
    I am wondering, has any microscopy been developed or is currently being developed that can see features in, say, a protein molecule that are just 0.2nm across (about two carbon atom-widths) while that protein molecule is in liquid water?
    -anyone?

    I know that, using "soft x-ray microscopy", it is possible to see features in a protein molecule whi ...[text shortened]... se the smallest feature that can be seen with light is half a wavelength of that light across.
    "I am wondering, has any microscopy been developed or is currently being developed that can see features in, say, a protein molecule that are just 0.2nm across (about two carbon atom-widths) while that protein molecule is in liquid water?"

    Only if the water isn't too wet.
  5. 30 Nov '10 18:19
    Originally posted by sonhouse
    I think you are dreaming! The best optical scopes can only go down to 200 nm, about a thousand time higher than the resolution you seek. It might be possible to do in in ice in an electron microscope but that is not water. I am thinking of having the protean stuck on the surface of an ice molecule to hold it in place then put that in a vacuum, the ice as cl ...[text shortened]... about that for sure. You might have a better chance with ice but that may defeat your purpose.
    “....I think you are dreaming! ….”

    I was hoping there may be some weird quantum effect that can be exploited in a way that gets round the awkward laws of physics (without actually breaking the laws of physics of course) to allow this?
  6. 30 Nov '10 18:25
    I know some people who are working on this. If I understand their work correctly, they don't use X-rays (wavelength too long, as you correctly state) but fast electrons. I don't think they have successfully mapped a protein molecule yet, though (in a time-resolved way, in solution rather than in crystal form).
  7. 30 Nov '10 18:30
    Originally posted by twhitehead
    My understanding is that it is possible to determine the shape of protein molecules but it is not easy nor cheap. The various projects to determine protein shapes via software prediction are partly to help develop custom molecules, but also to try and determine the shape of existing proteins quicker and easier than physical methods.

    If you looked aroun ...[text shortened]... and nuclear magnetic resonance (NMR)."

    http://boinc.bakerlab.org/rosetta/rah_about.php#why
    Thanks for that

    I knew about the “X-ray crystallography “ part but I was really surprised about the “...and nuclear magnetic resonance (NMR) ...” part! Implicitly didn't think NMR would be suitable for determining the structures of proteins but that shows how little I know.
  8. Standard member sonhouse
    Fast and Curious
    30 Nov '10 19:59
    Originally posted by Andrew Hamilton
    Thanks for that

    I knew about the “X-ray crystallography “ part but I was really surprised about the “...and nuclear magnetic resonance (NMR) ...” part! Implicitly didn't think NMR would be suitable for determining the structures of proteins but that shows how little I know.
    Actually, NMR probably has the best chance of a technology to do what you envision. The higher the magnetic field the better the resolution. Current technology puts the max DC field at around 15-20 tesla. If they get to around 100 tesla (admittedly a huge jump in field strength) the resolution will be on the order of angstrom units.
  9. 01 Dec '10 18:40
    Originally posted by sonhouse
    Actually, NMR probably has the best chance of a technology to do what you envision. The higher the magnetic field the better the resolution. Current technology puts the max DC field at around 15-20 tesla. If they get to around 100 tesla (admittedly a huge jump in field strength) the resolution will be on the order of angstrom units.
    Perhaps what is needed to make this happen is a 100 tesla magnet?
    Judging from the link I found below, I think such a thing will be produced soon!

    http://www.magnet.fsu.edu/mediacenter/features/meetthemagnets/multishot.html

    but this is very expensive and only produces the magnetic field for 15 milliseconds at a time.