DNA-binding proteins are proteins composed of DNA-binding domains and thus have a specific or general affinity for either single or double stranded DNA.
Sequence-specific DNA-binding proteins generally interact with the major groove of B-DNA, because it exposes more functional groups that identify a base pair. However, there are some known minor groove DNA-binding ligands such as netropsin,[distamycin, Hoechst 33258, pentamidine, DAPI and others.