 So it's tempting to think that we understand protein folding now but not so fast. First, this will only work for quite small proteins but there are some proteins that are large. The other problem is that as we talked about many proteins are quite hydrophobic and if the proteins are very hydrophobic what can happen is that they collapse so fast that the hydrophobic parts stick together and then they can't really fold. Nature has actually found ways to solve this by using proteins as always. This is a chaperone, grow EL and grow ES. The idea here is that if you are a small protein and you've gotten stuck because you've been a hydrophobic collapse we can take this entire protein it can diffuse into this complex there is a large hydrophobic cavity inside here. This complex will actually use ATP just as some of the pumps we spoke about in the membrane proteins. It will use the ATP to open up, change its conformation, then it will close this cap and then we have a hydrophobic environment in here and now my small protein will happily unfold a bit and hopefully have time to slowly fold into the right conformation and then it's going to be released by the chaperone again. Why do I show you that? Well partly to show that life is more complicated in practice but the other part is that we haven't solved this part with how fast proteins fold. Remember Cyrus Leventhal? We still have that problem right? I've just said that one way or another there should be a free energy path there so things should be able to fold but I haven't solved the fact that this needs to happen in finite time and there is no way the protein can test all those conformations. Go back and check the lectures on Leventhal's paradox if you don't remember that. So one way or another we need to understand why proteins can form fast and the second I say fast that means looking at the kinetics and how fast things happen literally. There could be a few smart ways. Remember the ribosome that we're having the RNA chain? Small subunit, large subunit and then the actual protein comes out here? Maybe just maybe we could have the if the end terminal comes out here first it would be really smart if proteins started to fold from the end terminal because then it's always a matter of the next structure I say the next amino acid that's going to be local we won't have to test every single possible combination. It's a beautiful model the only problem is that is wrong it doesn't work that way because remember that we could take a protein we could put it in water we could denaturate it and then it would spontaneously refold that is not compatible with the end terminals folding first. So Christian Anfinsen kind of proved this model wrong there are of course proteins where this happens but in general it's not true so we're still stuck that we haven't solved Leventhal's paradox and the only way we can understand kinetics is that we're going to need to start looking into a possible few possible candidate models how things might fold and then examine if they could explain why it is so fast and that's going to need to take us to a small odyssey of a few different models join me