text: The dissociation constant is commonly used to describe the affinity between a ligand  (such as a drug) and a protein ; i.e., how tightly a ligand binds to a particular protein.  Ligand–protein affinities are influenced by  non-covalent intermolecular interactions between the two molecules such as hydrogen bonding,  electrostatic interactions, hydrophobic and van der Waals forces. Affinities can also be affected by high concentrations of other macromolecules, which causes macromolecular crowding.
  The formation of a ligand–protein complex  can be described by a two-state process
  the corresponding dissociation constant is defined
  where , and  represent molar concentrations of the protein, ligand, and protein–ligand complex, respectively.
  The dissociation constant has molar units (M) and corresponds to the ligand concentration  at which half of the proteins are occupied at equilibrium, i.e., the concentration of ligand at which the concentration of protein with ligand bound  equals the concentration of protein with no ligand bound .  The smaller the dissociation constant, the more tightly bound the ligand is, or the higher the affinity between ligand and protein.  For example, a ligand with a nanomolar (nM) dissociation constant binds more tightly to a particular protein than a ligand with a micromolar (μM) dissociation constant.
  Sub-picomolar dissociation constants as a result of non-covalent binding interactions between two molecules are rare.  Nevertheless, there are some important exceptions.  Biotin and avidin bind with a dissociation constant of roughly 10 M = 1 fM = 0.000001 nM.
  Ribonuclease inhibitor proteins may also bind to ribonuclease with a similar 10 M affinity.  
  The dissociation constant for a particular ligand–protein interaction can change with solution conditions (e.g., temperature, pH and salt concentration). The effect of different solution conditions is to effectively modify the strength of any intermolecular interactions holding a particular ligand–protein complex together.
  Drugs can produce harmful side effects through interactions with proteins for which they were not meant to or designed to interact. Therefore, much pharmaceutical research is aimed at designing drugs that bind to only their target proteins (negative design) with high affinity (typically 0.1–10 nM) or at improving the affinity between a particular drug and its in vivo protein target (positive design).