Ligand screening and design by X-ray crystallography

A process for identifying a ligand which binds to a target biomolecule, wherein said target biomolecule forms crystals when bound to a ligand and wherein said target biomolecule does not form crystals when unbound to a ligand, said process comprising the steps of:

• a) exposing a target biomolecule to a mixture of at least two potential ligands;
• b) attempting to crystallize said target biomolecule in the presence of said mixture;
• and
• c) obtaining a crystal of said target biomolecule exposed to said mixture to determine whether a ligand/target biomolecule complex is formed.

A process for identifying a ligand which binds to a target biomolecule, wherein said target biomolecule forms crystals when bound to a ligand and wherein said target biomolecule does not form crystals when unbound to a ligand, said process comprising the steps of:

• a) exposing a target biomolecule to a mixture of at least two potential ligands;
• b) attempting to crystallize said target biomolecule with exposure to said mixture;
• c) if crystals are obtained, obtaining an X-ray diffraction pattern of said target biomolecule crystal with exposure to said mixture;
• and
• d) converting said X-ray diffraction pattern of said crystal into an electron density map using known phases of said target biomolecule crystal and determining whether a ligand/target biomolecule complex is formed from said electron density map.