There are 3 major types of tight binding modes between DNA binding dyes and DNA:

1. Intercalating (e.g. Propidium iodide)
2. Minor-groove binding (e.g. DAPI)
3. Bis-intercalating (e.g. YOYO-1)

Some dyes can bind to DNA’s major groove or externally bind with DNA through electrostatic interaction, though the binding is not as tight as the aforementioned three modes. Multiple binding modes can occur for one dye, and the dominant binding mode may change with different dye-DNA conditions such as dye-to-DNA ratio and DNA hybridization status.