How It Works? Circular Dichroism
A lot of modern research involves exploring the tiniest things in tremendous detail. Scientists can spend months and even years focused on a single protein.
Proteins are the molecular engines of our cells and much like mending a car the first step with developing therapeutic drugs is to understand how protein works. A hundred thousand times smaller than the cross section of a human hair, extremely small proteins are shaped like long necklaces with many beads. Shaped differently, these beads are called amino acids. Joined together they make thousands of protein structures that define their properties, function and activity.
Circular dichroism or ‘CD’ is a technique that offers researchers a way to look at this microscopic world allowing them to explore these tiny objects in an all-inclusive and dynamic way. It has helped to visualise the properties of proteins that underpin life and to design new drugs and smart materials.
What is it?
It’s all about light. As light waves move back and forth, the nature of these waves can change, so that they travel in a circular, elliptical or linear pattern. Scientists are not the kind to let opportunities pass them by, so we’ve developed ways of exploiting the interaction of light with matter for research. With a series of carefully-placed devices, we can force light waves to move in any way we want. This movement restriction is called ‘polarisation’. Our eyes can’t distinguish polarised light from unpolarised unlike some insects such as ants and bees.
CD involves polarising light waves so that they travel in a circular pattern. But that’s not all: we also manipulate the light waves so that they travel both clockwise and counter-clockwise at the same time, like two corkscrews intertwined. Scientists then shine this light onto a sample – such as a human protein or a chain of molecules. Atoms inside these samples absorb different kinds of light. By observing how much of the clockwise facing light is absorbed by the sample, compared to how much of the counter-clockwise light is absorbed, it’s possible to work out the type of structure of what it is we’re investigating.
To know how to fix a car a good mechanic would need to know in detail how the engine works. The same for biological systems: CD is used to obtain information about molecules and their interactions, which determine their properties, function and activity.
Scientists not only have a photo but a type of video which gives them more information about the system: a vital early step towards creating drugs that interact with the protein to combat disease.
Circular dichroism has a surprisingly long history, having been discovered in the 19th century by French scientists who observed the phenomenon by which objects absorb circularly polarised light in different ways depending on their structure.
By the 1950s, biochemists, molecular biologists and organic chemists had all realised the significance of this phenomenon for studying the intricate structure of matter. But due to its weak signal CD didn’t truly come into its own potential until synchrotron light sources became powerful enough to generate extremely brilliant light. Imagine the beam from a torch – the light scatters everywhere, creating a broader but dimmer light. If we polarise that light into a highly focused beam it’s much more concentrated and powerful.
The advent of machines like Diamond allowed us to produce powerful polarised light, vastly increasing the scope of CD research.
Circular Dichroism at Diamond
B23, Circular Dichroism Beamline at Diamond Light Source. Beamline users (L-R): Simon Patching, Mary Phillips-Jones, Shalini Edara, with Rohanah Hussain (DLS) and Giuliano Siligardi (DLS PBS)
Diamond has a beamline dedicated to circular dichroism (B23) with a highly focused and extremely small beam. Recently B23 helped researchers to uncover a key mechanism behind antimicrobial resistance by revealing the structure of a key protein complex that enables bacteria to survive attack (read more on page 4-5). This beamline has also been used to study how aroma products affect the quality of wine in fermentation and more recently taking advantage of the minute laser like quality of the beam, to map the coating of LED material paving the way for better fabrication.
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