ProteinLigand

Protein-ligand interactions describe the binding of a ligand to a protein, typically at a specific binding site, forming a protein-ligand complex. Ligands can be small molecules, ions, peptides, nucleotides, or larger cofactors. Binding is governed by noncovalent forces such as hydrogen bonds, ionic interactions, hydrophobic effects, and van der Waals contacts; covalent bonds occur in some cases.

Binding affinity is quantified by the dissociation constant (Kd) and is influenced by kinetics, including on-rate and off-rate. Specificity describes preference for a particular protein or site, though some ligands bind multiple targets. Proteins may change shape upon binding (induced fit) or select among conformations (conformational selection).

Functional outcomes depend on the system. Ligand binding can regulate enzyme activity, modulate receptor signaling, or control transcription. Allosteric ligands bind away from the active site to alter activity. Ligand binding is central to metabolism, regulation, pharmacology, and structural biology.

Study and applications: insights into protein-ligand interactions support drug design, discovery, and understanding of biological pathways. Experimental methods include X-ray crystallography, NMR spectroscopy, cryo-electron microscopy, isothermal titration calorimetry, and surface plasmon resonance. Computational approaches include molecular docking and molecular dynamics.

Examples: hemoglobin binds oxygen reversibly; enzymes use substrates as ligands and inhibitors as modulators; drugs such as statins and kinase inhibitors are designed to bind specific proteins.