Protein folding

Interactions between the side chains of amino acids determine how a linear polypeptide chain folds into the intricate three-dimensional shape of the functional protein. Protein folding, which occurs within the cell in seconds to minutes, involves nonrandom, ordered pathways. As a peptide folds, secondary structures form, driven by the hydrophobic effect (that is, hydrophobic groups come together as water is released). These small structures combine to form larger structures. Additional events stabilize secondary structure and initiate formation of tertiary structure. In the last stage, the peptide achieves its fully folded, native (functional) form characterized by a low-energy state (Fig. 1). [Note: Some biologically active proteins or segments thereof lack a stable tertiary structure. They are referred to as intrinsically disordered proteins.]

Figure 1:  Steps in protein folding (simplified).