 So you might think that compared to determining DNA structure and everything it should be easy to determine protein structures the same way well, the first protein structures appeared just a few years after the DNA structures, but that was a tour de force work by a number of groups in particular around the laboratory of molecular biology in Cambridge So one of the first structures to be determined was this one. It's hemoglobin And it's the molecule used to carry oxygen in our blood Max Perutz is the hero behind this one and it took them 22 years to discover it I can't even imagine today it's easy because we know that they have a unique structure that we can't determine But of course Perutz didn't know that so that they spent 22 years going after and cracking that problem Which I think is an amazing scientific achievement and the probably a sign of some astronomical stubbornness Here's a picture of Max and can you see that insanely large model there because again what we do in computers in two seconds They would have to do manually and carefully measuring with a ruler and then you have these rods going up so that you can push each atom and place the atom in a slightly different position and Then measure again and see does that correspond to the expected diffraction pattern that we would see in the experiment Although this was done without computers It's very much the type of modeling I spoke about you come up with the model you test your model You should be careful not to fall in love with your model And then you assess your model against the toughest experimental results you can find and of course when you're successful You tend to change science such as Max did here Today we're blessed enough that we have many more proteins the with no structure than when I was your age I think Stuart Forsen and Lund for whom I took biophysical chemistry in the mid 1990s early 1990s Even he had a strike out the line in the lecture compendium that there were like 30 known protein structures I said that there's almost 300 now an amazing amount of them Well today there are well over hundred thousand and since the day I took this We even have structures of membrane proteins That might not sound remarkable to you, but the first structures of membrane proteins was bacteria rhodopsin And that appeared a few years before I was a PhD student KCSA iron channels 1998 that was while I was a PhD student the first ever iron channel structure determined This is the corresponding human protein. There's actually a trend here. This is kind of the Conceptually the same channel, but a prokaryotic protein is somewhat smaller and the eukaryotic one is somewhat larger We're gonna come back to that later on They've been both in love stories in different parts of my life This is another membrane protein aquaporin, which is the channel that is regulating water contents in and out of cells There are actually a bunch of aquaporins that are present in your eyes and others I won't have time to go through them all but super important discoveries and Rod McKinnon and Peter Ager They shared the 2003 Nobel Prize for chemistry for these discoveries The GPCRs that are already mentioned Brian Krabilka shared the Nobel Prize with his advisor for this in 2012 and Ray Stevens has also done very important contributions to pharmaceutical design of this and it might sound stupid that we're getting awarding so many Nobel Prize of these protein structures, but it's literally Before we have these structures. It's like a black box. We know that they're doing something But we have no idea why or how the second we have these structures even when there are somewhat low resolution We can usually describe the entire molecular process and understanding. Aha It's binding something up here that is changing the protein to another stage Which is releasing the signal here on the other side and that in turn is then used to say design drugs and alter This behavior of a particular protein So make no mistake. I think that we're gonna keep seeing Nobel Prizes awarded in structural biology