Hsien Wu and the First Theory of Protein Denaturation (1931)

Publisher Summary This chapter presents the paper by Hsien Wu, who was the first scientist to grasp the fundamental relations between the native and the denatured state of protein molecules. It also provides a brief account of his life. In the course of formulation of his protein denaturation, he had experimented with almost all the modes of denaturing proteins. The critical point of Wu's theory is that a native protein molecule is a highly compact and well-ordered structure, held together primarily by interactions between polar groups in the main chain and in polar side chains. The molecule, therefore, can be thought of as a sort of submicroscopic crystal, and the forces that hold the native protein molecule together in a defined configuration are the same as those causing the protein molecules to pack together in a macroscopic crystal. When the protein becomes denatured, and the molecule unfolds into a more or less open chain, it can assume an enormous number of possible configurations (or conformations, in the terminology of today) and specificity is lost, although it can be restored by reversal.