Modifying single proteins (GPCR), ligands, and nanopore surfaces to create binding-induced molecular changes of protein-ligand complexes detected in 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 an association of molecules with different structures, the method comprising:
translocating the molecules 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; measuring one or more electrical signals through, across, or both through and across the one or more nanochannels for every event, the event being a translocation event, a binding event, or both the translocation event and the binding event; and determining that at least two different molecules have combined into a combination based on a change in the one or more electrical signals, a change in translocation time for the translocation event, or both a change in the one or more electrical signals and in the translocation time for the translocation event; wherein the proteins are G-protein coupled receptors.