The present invention provides methods for the identification of target molecules that bind to ligands, particularly microRNA ligands and mimics thereof and/or microRNA target molecules and mimics thereof, with as little as millimolar (mM) affinity using mass spectrometry. The methods may be used to determine the mode of binding interaction between two or more of these target molecules to the ligand as well as their relative affinities. Also provided are methods for designing compounds having greater affinity to a ligand by identifying two or more target molecules using mass spectrometry methods of the invention and linking the target molecules together to form a novel compound.