Multitudes Making Magnificent Movies Of Molecules
A new technique using Crystallography allows researchers to make movies of molecules in such a way that hundreds or thousands of labs worldwide will now be able to perform this feat instead of just 3.
Do you know what crystallography is? I hadn’t appreciated its full significance until I started researching this news-item and it’s fascinating. So how does it work?
The arrangement of atoms in molecules and macromolecules (like biological molecules) cannot be seen using visible light because the wavelength of regular light is around 3 orders of magnitude too large to resolve them. We need light with a shorter wavelength and it turns out that x-rays fit the bill nicely. The Crystallographic process shines a thin x-ray beam through a crystal which scatters the light into many beams which are projected onto a screen. This distinctive pattern of diffracted light is run through carefully crafted equations which relate the pattern on the screen with the specific pattern of atoms in the crystal itself. If you’re thinking that bio-molecules aren’t crystals you’d be right but they can be imaged using this technique by putting them in a special solution (which uses vapor-deposition) to slowly crystallize them.
This process sounds fairly straightforward but it is arguably one of the greatest innovations of the 20th century. Using it we have elucidated the structure of many of the most important biological structures known to science from vitamins (like vitamin C), to drugs (like morphine), proteins, and that Ferrari of bio-molecules….DNA itself. So important is crystallography that no less than 28 Nobel prizes have gone to scientists whose experiments relied critically on it. So what has crystallography done for us lately? It is still the premier method for determining the atomic structure of almost anything. It is being used now to determine the structural weak-points of the Ebola virus that future drugs may be able to use to disable it. It is being used by the Curiosity rover on Mars right now to analyze its soil. Oh, by the way, 2014 is the International Year of Crystallography…seriously.
This is the x-ray crystallographic image that chemist Rosalind Elsie Franklin took in the early 1950’s. According to Francis Crick, this image and related research were instrumental in proving the double-helix structure of DNA and for the ultimate creation of their DNA model described in their famous paper.
Determining the structure of molecules is of course incredibly helpful but to fully understand what these marvelous nano-machines do, a static image of the structures is not enough. You need to see them in action. Imagine trying to figure out everything you can about a mechanical wrist watch based simply on images of its mechanical structure. You’d only be able to learn so much. Imagine how useful it would be to actually see what the watch does while it’s working.
Turning static crystallographic images into a home-movie of sorts has already been accomplished actually. This is called Time-Resolved Crystallography. It works by laboriously building up images one at a time similar to a stop-motion movie. This is achieved by synchronizing a bunch of identical molecules so they are all in the same state. They then “pump” the molecules which activates them into performing their natural functions. After a set period of time a conventional crystallographic image (called a “probe”) is taken. This process is then started all over but instead, the image is taken a little later in the process. In this
way, a movie is built up of the molecules doing their jobs. This is great and all except there is a problem with this so-called Pump-Probe technique. The exposures for the images are necessarily very brief, on the order of 100 trillionths of a second. This is such a tiny slice of time that you need a very bright, powerful, and pure source of x-rays to capture an adequate image. You can’t buy those suckers on eBay, in fact only 3 labs on earth have powerful enough x-ray generators (synchrotrons) to create the x-rays required for these molecule movies.
Progress using this technique has therefore been slow over the years. What if hundreds or thousands of labs around the world had this ability using the lower power generators that they already have right now? That is exactly what is being reported in the journal Nature Methods this past October 5th.
This new technique is similar to the one I just mentioned in that the molecules are synchronized and then activated (pumped). The “probe” though that is performed next is not one single high powered beam of x-rays but a series of low-powered pulses that build up an image similar to a long exposure created by conventional consumer cameras. This process is then repeated using a different pattern of pulses to build up a different “long exposure image”. This process is repeated yet again until all the mathematically required patterns of pulses have been used. The end result is a series of blurred images that can then be used to pull out a moving picture of how the structure of a molecule changes over time as it performs its molecule tasks.
With more researchers, scientists, and engineers now able to make movies of molecules and macromolecules, the process of linking structure, dynamics, and function together could potentially proceed at a pace never before seen. The result could accelerate a host of breakthroughs such as the design of new and better drugs with fewer side effects. It could also impact other disciplines such as Materials science which has the potential to impact our lives is even more diverse ways.
Not bad for just some x-rays and a crystal.