bindingsite

A binding site, sometimes written as binding-site or bindingsite, is a region on a biomolecule—most often a protein or nucleic acid—where a ligand binds to form a complex. In proteins, binding sites are typically pockets or grooves whose shape and chemical environment confer selectivity for specific ligands such as substrates, cofactors, inhibitors, or signaling molecules. Binding can be reversible, relying on non-covalent interactions, or, less commonly, covalent.

Key features of binding sites include geometry, chemistry, and dynamics. Complementarity between the site and ligand—shape, hydrophobic/hydrophilic balance, and the arrangement of hydrogen bonds and ionic interactions—stabilizes the bound state. Binding sites are often categorized as orthosteric (where the primary ligand binds) or allosteric (modulating function when bound elsewhere); catalytic active sites are specialized binding sites that also perform chemical transformations. Some proteins contain metal-binding or nucleotide-binding sites, and others have multiple sites enabling cooperative binding or regulation.

Characterization and discovery rely on structural biology and biophysical methods. Techniques such as X-ray crystallography, cryo-electron microscopy, and NMR reveal site location and geometry, while methods like isothermal titration calorimetry, surface plasmon resonance, and microscale thermophoresis measure affinity and kinetics. Computational approaches, including binding-site prediction, molecular docking, and molecular dynamics, aid in hypothesis generation and design. Understanding binding sites underpins structure-based drug design and protein engineering, guiding the development of inhibitors, activators, or engineered enzymes. Examples include the catalytic active site of serine proteases and the ligand-binding pockets of G protein–coupled receptors.