Conformation Changes Everything

Biodesy’s technology directly and dynamically measures protein conformational change in high throughput. Our vision is to help transform our understanding of how proteins work, by enabling the study of all relevant interactions of dynamic, functional proteins.

 

How our technology works


Biodesy’s technology is based on an optical phenomenon called Second Harmonic Generation (SHG). The protein is labeled with proprietary dyes conjugated to either amines or thiols. Labeled protein is then tethered to our lipid bilayer surface via His-tag. Our dyes generate second harmonic light upon stimulation by a femtosecond laser. The intensity of the signal is highly sensitive to the average angular orientation of the dye, enabling measurement of magnitude and direction of conformational change. Even sub-Ångström shifts cause detectable signal change. SHG signal is not affected by mass or structure, so our technology is amenable to proteins of varying molecular weight and ligands ranging from small fragments to protein complexes, including antibody/antigen interactions.

 

Conformational signatures


The sensitivity of SHG to conformational change enables more precise measurement than previously possible. Conformational signatures can be determined based on direction, magnitude and kinetics of conformational change. Since many conformational changes cause changes in protein function, conformational signatures can classify and distinguish interactions based on both structural change and functional consequence.

Conformational Change

 

High value in high throughput

The use of structural information in protein analysis has been limited by cost and throughput. Understanding function of a single protein requires the testing of many interactions and conditions. SHG is easily amenable to high throughput, and the Biodesy Delta system enables the large scale experiments required to test and map those interactions. In some cases, protein availability is also limited. Biodesy Delta requires less than 1 µg of protein per measurement, which is substantially less than existing structural techniques. By using less protein per experiment, the Biodesy Delta can enable more conditions to be studied.

 

Publications