Protein geometry as a function of time

The title of this talk is intentionally obscure since the range of tim e to be discussed is not given. The talk will start with decades (i.e. history). What did a protein look like in the 1940s? What were the methods that provided the “pictures&rdquo? What mathematical support was useful? How did the problems of protein structure develop in the ensuing decades? Protein stability - reduce the time scale from decades to days or minutes. What did “denaturation” mean in the 30's through the &ldq uo;50”s? What does it mean today? What did the molecular biology revolution do to our views of the structure of proteins? A multiple answer question. The genes and their immediate products are linear polymers. The comparison and analysis of simple linear lists of characters has absolutely required the development of new mathematical tools to even get off the starting blocks. Data acquisition, data banks, and data analysis are all moving along in high gear. The problems produced by the division of science into smaller and smaller sections each with its own developing vocabulary are increasing exponentially. Today chemical investigations can be carried out at the femtosecond time scale. Do we on the biological side really care. Most of biology is in the micro to multisecond range or longer, but even macromolecules have important functions in the picosecond region. Refinement of X-ray structures is not as good as it should be. Where is the problem? NMR like all other spectroscopic procedures has an intrinsic time base. X-ray diffraction is better for static structures, NMR should spend much more of its effort on time specifications where, in principal, it beats the X-ray procedures hands down. Cryoelectron microscopy is pushing spatial resolution to lower and lower limits. Bridging the gaps between the EM and the X-ray/NMR regions in both space and time requires major mathematical help. As solutions to some of these problems appear, the problems are simply made worse