The complex interactions of a polypeptide molecular chain with its environment and itself and other protein entities, which cause the polypeptide molecule to fold up into a highly organized, tightly packed, three-dimensional structure. Proven to occur spontaneously, by Christian B. Anfmsen during the 1960s; for protein molecules outside of living cells. This ability of polypeptide chains to fold into a great variety of topologies, combined with the large number of sequences (in the molecular chain) that can be derived from the 20 common amino acids in proteins, confers on protein molecules their great powers of recognition and selectivity. How a protein folds up determines its chemical function. During the 1990s, it was discovered that inside living cells, “chaperone” molecules are needed for proper protein folding to occur. These chaperones are protein molecules (e.g., certain heat-shock proteins) that form a loosely bound complex to suppress incorrect protein folding as the protein molecule is emerging from the cell’s ribosome, so protein folding is both complete and correct as soon as the newly formed protein molecule is released from the cell’s ribosome.