FIND platform screens molecular modulators with DNA nanoswitches in vitro
Researchers combined DNA nanoswitch selection with sequencing to identify compounds that induce or enhance protein-protein interactions.
Researchers developed Functional Interaction–based Nanoswitch Discovery (FIND), an ultrahigh-throughput screening platform that identifies compounds modulating protein-protein interactions, as reported in Science science.org
Sciencescience.orgOpen source ↗. The method combines DNA nanoswitch–based selection of nucleotide-encoded libraries with next-generation sequencing to directly detect multibody molecular interactions and ternary complex formation.
The authors demonstrated the platform in vitro by screening for molecules that influence specific target proteins. The team used FIND to discover nanobodies that stabilize the interaction between angiotensin-converting enzyme 2 (ACE2) and the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Additionally, the workflow identified peroxisome proliferator–activated receptor gamma agonists from a DNA-barcoded small-molecule library.
Standard screening techniques often lack sufficient throughput or struggle to directly analyze multibody interactions. According to the authors, the approach provides a rapid mechanism to discover molecular modulators that induce or increase targeted protein complexes.
