The Shape of Proteins to Come

A new technique allows scientists to see conformational changes caused by ligand binding in real time, opening up new screening options for drug discovery.

By Charlotte Barker

Protein conformational changes play a key role in signaling (after all, changes in shape cause changes in function); however, it has been difficult to study those changes in real time. Crystallography, dual polarization interferometry, and binding assays have all been used, but inherent limitations have curtailed widespread use. Now, with a new technique based on the optical principle of second harmonic generation (SHG), biophysics start-up Biodesy hopes to put conformational data in the hands of scientists around the world. Investors currently include pharma giants Pfizer and Roche – and Biodesy’s first commercial system launched in January 2016.

The technique involves labeling the protein of interest with proprietary dyes and tethering them to a lipid bilayer surface (Figure 1). A femtosecond laser is applied, causing the dyes to generate second harmonic light. The intensity of the signal correlates with the position of the label relative to the surface, and hence the magnitude and direction of the conformational change can be calculated.