Modifying proteins (gpcr), ligands, and nanopore surfaces to allow the detection of create binding-induced molecular changes of protein-ligand complexes with nanochannel translocation

A method for determining binding capability of a target ligand with a G protein-coupled receptor comprising:

• introducing the target ligand to the G protein-coupled receptor;
• translocating the target ligand and the G protein-coupled receptor partially or entirely through one or more nanochannels filled with an electrolyte solution based on an electric potential difference applied in a longitudinal direction of the one or more nanochannels to define an event;
• measuring one or more electrical signals for every event, the event being at least one translocation event, at least one binding event, or a combination of at least one translocation event and at least one binding event, the one or more electrical signals determined by at least one signal being measured through, across, or both through and across the one or more nanochannels;
• and
• determining that the target ligand and the G protein-coupled receptor are bound to one another based on a change in the one or more electrical signals and a change in translocation time for the translocation event.