The process by which a linear chain of amino acids spontaneously arranges itself into a specific three-dimensional structure. This folded shape—not just the sequence—determines whether a peptide or protein can bind its target receptor, catalyze a reaction, or perform its biological function.

Misfolded proteins are implicated in diseases including Alzheimer’s (amyloid plaques), Parkinson’s (alpha-synuclein aggregates), and prion diseases. In the peptide world, folding matters for stability: a properly folded peptide resists enzymatic degradation longer than an unfolded one, which is why cyclic peptides and disulfide-bonded peptides tend to have longer half-lives.