MODIFYING PROTEINS (GPCR), LIGANDS, AND NANOPORE SURFACES TO ALLOW THE DETECTION OF CREATE BINDING-INDUCED MOLECULAR CHANGES OF PROTEIN-LIGAND COMPLEXES WITH NANOCHANNEL TRANSLOCATION

摘要

A mechanism is provided for utilizing a nanodevice to distinguish molecules with different structure. The molecules translocate through or across a nanochannel filled with a electrolyte solution. An electrical signal through the nanochannel is measured for every translocation event. Inner surfaces of the nanochannel include a functional layer, which is a coating to functionalize the nanochannel, in which the functional layer is configured to interact with predetermined ones of the molecules during translocation events. It is determined that a combination of at least two different molecules is formed based on predetermined ones of the molecules interacting with the functional layer to change the electrical signal and/or change a translocation time for the translocation event.

主权项

1. 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.