HYBRID is a docking program that also uses elements of ligand based design to enhance performance. Typically, the protein structure is determined with X-ray crystallography in the presence of a known binding ligand (or bound ligand). The HYBRID program uses the information present in both the structure of the protein and the bound ligand to enhance docking performance. HYBRID requires that the structure of a bound ligand be known, if it is not known FRED can then be used to do traditional docking.

HYBRID also allows multiple structures/conformations of the target protein to be used. In this case HYBRID will determined the best structure/conformation to use for each ligand in the docking database.