Large conformational changes in proteins: signaling and other functions

Guanine and adenine nucleotide triphosphatases, such as Ras proteins and protein kinases, undergo large conformational changes upon ligand binding in the course of their functions. New computer simulation methods have combined with experimental studies to deepen our understanding of these phenomena. In particular, a ‘conformational selection’ picture is emerging, where alterations in the relative populations of pre-existing conformations can best describe the conformational switching activity of these important proteins.