Gold nanoparticles have unique optical properties arising from their ability to support localized surface plasmonc resonance.Gold nanoparticles are also well-known by their ability to alter the emission properties of proximal fluorophores,due to F(o)rster resonance energy transfer (FRET),nanomaterial surface energy transfer (NSET),or electron transfer,depending on the distance of the fluorophores to nanoparticle surface and the emission wavelength of the fluorophores.In previous studies,we have developed a series of metal nanoparticles based bioassays for studying various biomolecular binding events,concerning DNA mutation [1-3],gene transcription [4,5],enzymatic cleavage of DNA,and aptamer selection [7],by exploiting interparticle distance determined plasmonic property.In this study we have combined gold nanoparticles fluorescence quenching properties and protein-DNA binding induced hybrid assembly between gold nanoparticles and fluorescent materials for efficient study of transcription factor-DNA interactions and ligand inhibition that are important for breast cancer research and drug discovery.The results are compared with those using conventional biological analysis methods,i.e.EMSA and fluorescence anisotropy,as well as instrument based methods (dual polarization interferometer and surface plasmon resonance spectroscopy).With the conventional methods as reference,we concluded that the gold nanoparticle-fluorophore hybrid sensors have higher sensitivity to determine subtle affinity difference induced by single base mutation in DNA elements and to report strong and weak ligand interruption.Understanding the DNA binding property and ligand effects of these transcription factors is of significant for breast cancer and drug discovery research.