Proteins are complex entities created from 20 types of amino acids. e diverse functionality of proteins originates from the spatial organization of the protein chain. is brings residues that are far from sequence into proximity and enables the coordinated action of chemical groups. e cleavage of an amide bond, for example, requires an attacking nucleophile and a general acid to activate the nucleophile. Although the variety of three-dimensional architectures (i.e., folds) results in versatile functions, the static arrangement of amino acids cannot fulll even the simplest biological activity. Binding of oxygen to hemoglobin would be hindered by steric conicts unless protein sidechains change their position to create a free path toward the heme group.