Biophysical characterization of proteins in the post-genomic era of proteomics

Proteomics focuses on the high throughput study of the expression, structure, interactions, and, to some extent, function of large numbers of proteins. A true understand-ing of the functioning of a living cell also requires a quan-titative description of the stoichiometry, kinetics, and en-ergetics of each protein complex in a cellular pathway. Classical molecular biophysical studies contribute to un-derstanding of these detailed properties of proteins on a smaller scale than does proteomics in that individual pro-teins are usually studied. This perspective article deals with the role of biophysical methods in the study of pro-teins in the proteomic era. Several important physical biochemical methods are discussed briefly and critiqued from the standpoint of information content and data ac-quisition. The focus is on conformational changes and macromolecular assembly, the utility of dynamic and static structural data, and the necessity to combine ex-perimental approaches to obtain a full functional descrip-tion. The conclusions are that biophysical information on proteins is a useful adjunct to “standard ” proteomic methods, that data can be obtained by high throughput technology in some instances, but that hypothesis-driven experimentation may frequently be required. Molecula