Ligand (biochemistry)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose.
Measurably irreversible covalent bonding between a ligand and target molecule is atypical in biological systems.
Ligand binding to a receptor protein alters the conformation by affecting the three-dimensional shape orientation.
Ligand affinities can also be measured directly as a dissociation constant (Kd) using methods such as fluorescence quenching, isothermal titration calorimetry or surface plasmon resonance.
In this example, the concentration at which the full agonist (red curve) can half-maximally activate the receptor is about 5 x 10−9 Molar (nM = nanomolar).
[5] Real-time based methods, which are often label-free, such as surface plasmon resonance, dual-polarization interferometry and multi-parametric surface plasmon resonance (MP-SPR) can not only quantify the affinity from concentration based assays; but also from the kinetics of association and dissociation, and in the later cases, the conformational change induced upon binding.
MP-SPR also enables measurements in high saline dissociation buffers thanks to a unique optical setup.
[7] For the use of statistical mechanics in a quantitative study of the ligand-receptor binding affinity, see the comprehensive article[8] on the configurational partition function.
Binding affinity data alone does not determine the overall potency of a drug or a naturally produced (biosynthesized) hormone.
This class of ligands was pioneered by Philip S. Portoghese and coworkers while studying the opioid receptor system.
[14][15][16] Bivalent ligands were also reported early on by Micheal Conn and coworkers for the gonadotropin-releasing hormone receptor.
Recent research shows that the type of ligands and binding site structure has profound consequences for the evolution, function, allostery and folding of protein compexes.
[32][33] A privileged scaffold[34] is a molecular framework or chemical moiety that is statistically recurrent among known drugs or among a specific array of biologically active compounds.
For example, a worldwide grid of well over a million ordinary PCs was harnessed for cancer research in the project grid.org, which ended in April 2007.
