Protein-Ligand Interactions

Interactions between proteins and Ligands are of fundamental importance in cellular metabolism since it is via these interactions that proteins carry out their myriad functions. Detailed knowledge of how these interactions work on a micro-and macroscopic level is therefore required. Some examples of protein-ligand interactions include: antigen-antibody binding; enzyme-substrate interactions; ligand binding to structural proteins; protein-DNA binding; protein-saccharide, protein-protein, and protein-peptide interactions.

One of the earliest models of protein-ligand binding is the lock and key model, proposed by Fischer in the 1890s.^[1] In this model, the enzyme has an active site which is like the keyhole of a lock, and the ligand is the key that fits in this keyhole. The lock and key model was proposed before it was known that proteins are dynamic entities and does not take into account the inherent flexibility of the folded protein.

A more up to date model is the induced fit model^[2] which takes into account this flexibility and the conformational changes that occur upon ligand binding. It is analogous to the lock and key model, but instead of the lock and key fitting together perfectly, both change conformation slightly to improve the fit.

Planted: Friday 24 February 2023
Last tended: Monday 23 June 2025