Patent ID: 8080379

Claim:
A method of chemical screening comprising: providing a bistable branched switch, comprising DNA, RNA, modified nucleic acid, or combinations thereof, wherein the branched switch is adapted to switch from a first conformation to a second conformation upon ligand binding, said switch comprising: a probe strand P comprising a ligand binding domain; a switching framework comprising a cover strand (C), which is partially but not completely complementary to P; a tether that holds P and C together while the switch changes between the first and second conformations without dissociating the branched nucleic acid thereby creating a rapidly reversible switch; a toggle strand (T) tethered to the P-strand and the C-strand by covalent linkage; and a signaling apparatus comprising a combination of signaling entities, wherein a ligand for the ligand binding domain is selected from the group consisting of proteins, cell-surface features, and small molecules, and wherein the ligand binding domain is sequestered in the first conformation; contacting the branched switch with the ligand in the absence of a screened chemical entity; monitoring a signal produced from the signaling apparatus in the absence of the chemical entity; contacting the branched switch with the ligand in the presence of the chemical entity; monitoring a signal produced from the signaling apparatus in the presence of the chemical entity; and comparing the signal produced in the absence of the chemical entity with the signal produced in the presence of the chemical entity to determine the effect of the chemical entity on the ligand binding.