High-Throughput Structural Insights

Biodesy’s technology directly and dynamically measures structural changes of biological molecules in high throughput. Our vision is to help transform our understanding of how biomolecules work, by enabling the study of all relevant interactions of dynamic, functional biomolecules.

 

How our technology works

SHG_BeanSchematic_02062019


Biodesy’s technology is based on an optical phenomenon called Second Harmonic Generation (SHG). The biomolecule is labeled with proprietary dyes conjugated to either amines or thiols. Labeled biomolecule 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 the magnitude and direction of structural changes. Even sub-Ångström shifts cause detectable signal change. SHG signal is not affected by mass or structure, so our technology is amenable to biomolecules of varying molecular weight and ligands ranging from small fragments to protein complexes, including antibody/antigen interactions.

 

Conformational signatures


The sensitivity of SHG to structural change enables more precise measurement than previously possible. Conformational signatures can be determined based on the direction and magnitude of structural changes. 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 biomolecule analysis has been historically limited by cost and throughput. Existing structural techniques, such as x-ray crystallography and NMR, require significant time and resources, limiting their utility to a few primary candidates. However, SHG enables high-throughput analysis of biomolecules to gain early structural insights into biomolecular function.

 

Leveraging SHG for drug discovery

BlueLight Therapeutics is a branch of Biodesy focused on leveraging our novel platform to drive drug discovery on high-value, challenging drug targets.

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Publications