In biochemistry and pharmacology, a ligand is a substance (usually a small molecule) that forms a complex with a biomolecule to serve a biological purpose. In protein-ligand binding, the ligand is usually a signal-triggering molecule, binding to a site on a target protein. In DNA-ligand binding studies, the ligand is usually any small molecule or ion, or even a protein that binds to the DNA double helix. The binding occurs by intermolecular forces, such as ionic bonds, hydrogen bonds and van der Waals forces. The docking (association) is usually reversible (dissociation). Actual irreversible covalent bonding between a ligand and its target molecule is rare in biological systems. In contrast to the meaning in metalorganic and inorganic chemistry, it is irrelevant whether the ligand actually binds at a metal site, as is the case in hemoglobin. Ligand binding to a receptor (receptor protein) alters its chemical conformation (three-dimensional shape). The conformational state of a receptor protein determines its functional state. Ligands include substrates, inhibitors, activators, and neurotransmitters. The tendency or strength of binding is called affinity. Binding affinity is determined not only by direct interactions, but also by solvent effects that can play a dominant indirect role in driving non-covalent binding in solution. Radioligands are radioisotope labeled compounds are used in vivo as tracers in PET studies and for in vitro binding studies.