Researchers from Canada’s National Institute for Nanotechnology and Stanford University have developed a technique to measure the route a biological molecule takes during the formation of its three dimensional structure. Using laser optical tweezers, they have made precise measurements of the folding process of a DNA strand which they interpreted to map out the energies that govern the route taken during the folding process. The findings are described in the November 10 edition of Science.
Biologically active molecules like proteins and nucleic acids (DNA and RNA) have very specific functions in living organisms, and those functions depend upon shape of the molecules. New structures are being formed all the time in a living organism by the folding and unfolding of the molecules and understanding the folding process is crucial to understanding how the structures are formed.
Structural form is so closely tied to molecular function that when folding does not occur properly the result can be very serious. Mad Cow disease (BSE), Lou Gehrig’s disease (ALS), and Alzheimer’s disease are all caused by improper folding that leads to shape with a harmful function. Understanding how folding works could eventually lead to treatments that ensure correct folding.
The ‘mapping’ described in the paper was done by measuring changes in the energy landscape of the molecule as it folded and the unfolded, similar to measuring changes in elevation during a car road trip. The shape of the energy landscape governs the route taken by the folding molecule.
The new technique provided several improvements in data collection because it was more precise, more controlled and could be make repeated measurements of thousands of events. Because of these advances, it is now possible to trace the whole route taken during folding, allowing researchers to perceive the entire process from beginning to end.
“We’ve developed a new and more complete way to measure the fundamental properties governing how biological molecules take their 3-D structure,” explains Dr. Michael Woodside. “This technique should help scientists gain insight into how these molecules work and what goes wrong in misfolding diseases.”