 So the first multi globulae is this one, nuclear co-activator binding domain and it's a study by Flemming-Polson in Denmark a few years ago. The NMR structure here means that we have an entire ensemble of structures insolvent and well as you see there are a couple of well-defined helices and everything but then you have all these loops and they're a bit floppy and in particular the region out here every structure is pretty much different. I'll show you that it's actually worse in practice because it's not just these backbones if I start to draw all the side chains here it's almost a mess. So the side chains are slightly different in all these structures but there is an overall structure it's not just random amino acids on the inside as I kind of lied to you and told you that the high of the molten globula was. So the molten globulae is that I've taken the protein and expanded it a bit. Do you see here the inside? It's kind of water accessible in here so I've destroyed the protein a bit apparently if water is able to enter the inside the secondary structure elements are still there but it's not quite as well defined and this is a very typical molten globulae. I'll show you some other examples before we summarize them. This is a cytochrome domain you can see the heme group there in the middle. In this case what research has done is that they've shot a laser on the structure and then you can track the structures even on nanosecond level and we're going to see what happens in nanosecond level and unfortunately these plots are a bit small but we see roughly the same things happening there. So within a few nanoseconds we're gradually starting to see some helices becoming a little bit distorted you can probably see that here right that one helix is starting to tilt up a little bit and roughly here in the middle there's a helix tilting even further up. So maybe not quite as dramatic changes here but it's definitely changing and here is another NMR structure. In this case there almost doesn't appear to be any structure left but there is some sort of middle region here that's roughly aligned and there are likely some interactions between the amino acids but in this particular case we've lost all the secondary structure. So let's summarize this in a table. The molten globulae it turns out that this is a bit of Dr. Jekyll and Mr. Hyde. It has some properties that makes it like a native protein and other properties where it's more like the coil or unfolded. So it certainly has a compact hydrophobic core as you saw from these structures. On the other hand the structure is not rigid so it doesn't have this beautiful packing that has enabled us to determine crystal structures of proteins for instance. We have secondary structure again you saw the helices in those at least in most cases they were a bit floppy in some of them. There is no real no what should I say there is no all or none transition to coil. What I mean by that is that this phase transition the magic thing that happens that happens between the molten globulae and the native state. Once you are in the molten globulae it's much much much smoother to completely unfold. So we've by the time you're in the molten globulae we've lost the magic. You're no longer a protein and you're not going to have any beautiful function. We'll look at that later. We have some partial side chain side chain order. Triptophan molecules for instance they're buried like they should be remember the TRPK protein. But there is no unique packing again a protein structure should be unique but remember those NMR structures I just showed you they're different in all of them. We might have at least some disulfide bridge formation but the really bad thing is that it's not a functional protein so it doesn't work yet. So what we want to start by understanding here is that if we're going first from the fully stretched out state in a chain what is it that makes us reach the molten globulae first? That's going to be the first challenge and it turns out that some things that are specific to proteins such as being a chain is important already there. The second step we're going to look at today is that what is it that makes us go from this molten globulae to actually become a real protein that also is functional.