Patent ID: 8192999

Claim:
A method for determining the identity of an unknown protein target of an analyte said method comprising: a) contacting said analyte with a sample comprising a plurality of macromolecules so as to allow binding of said analyte to the unknown protein target thereby generating an analyte-target complex wherein the analyte and protein target are underivatized and free in solution; b) next resolving said macromolecules including said analyte-target complex liquid chromatography to produce macromolecule fractions, wherein binding of said analyte to said protein target is maintained during said resolving and said resolving takes place under non-denaturing conditions; c) analyzing a plurality of the macromolecule fractions including at least one macromolecule fraction containing the analyte-target complex to identify fractions that contain the analyte; d) analyzing at least one macromolecule fraction that contains the analyte with mass spectrometry to determine the mass spectrum and the identity of the protein target, wherein the macromolecule fraction that contains the analyte is subject to proteolytic degradation prior to analyzing the macromolecule fraction with mass spectrometry.