induced fit

A binding pocket is not a rigid stamped hole; it is more like a soft glove that reshapes itself when you push your hand in. Induced fit describes how a protein target adjusts its conformation as a ligand binds — side chains swing aside, loops close down, helices shift — so that the final fit is tighter than the empty pocket alone would allow. The lock changes to grip the key.

Mechanistically, induced fit usually means the ligand first makes contact with the protein in one shape, and the resulting interactions pay for and stabilize a conformational change in the target. A famous example is the activation loop and 'DFG' motif of kinases, which can flip between conformations and let inhibitors reach pockets that are invisible in a single static structure.

Induced fit matters because it both creates opportunity and complicates prediction. New cryptic or 'induced' pockets can offer fresh selectivity, but a flexible target is hard to model: docking against one rigid snapshot can miss binders that would only fit after the protein moves. It also has an energetic cost — the protein must give up favorable contacts or strain itself to rearrange, which the ligand binding has to outweigh.