 The stability of a protein fold that we just looked at describes whether a stretched out denatured chain would like to fold and be stable in that particular conformation. That is intimately related to the question of whether an already stable protein under some conditions would like to make a structural transition to another state depending on the surrounding conditions. I'm going to tell you a little bit about that because it's a very interesting concept from a functional point of view. This is a protein I studied many years ago with computations. It's called glutamate binding protein and it binds a small molecule. Can you imagine what it binds? That's right, glutamate, the yellow one there. In general if a protein binds a molecule there are three conceptual models that we've used over the years. The first one I will only touch upon because it doesn't really involve any conformational transition. But what if I had a protein that just happens to fit perfectly like a lock to a key. So I have a small molecule and that molecule is the key and enters the lock. The lock and key hypothesis. In practice we virtually never see that. Maybe maybe you could argue that some of these DNA binding proteins would fit there because they fit the DNA major groove almost perfectly. In practice what we frequently have though is something we're called induced fit. Let me just write lock and key first. Induced fit would correspond to having a protein that maybe has a spherical interior or something. And then we have that square molecule. That molecule is not going to fit. However, if I force that molecule, the square molecule into the protein, the protein might then change its shape so that it would induce a conformational change. And that we tend to call induced fit which is quite common. It was one of the first original ideas about how ligands in drug design works. I'll come back to that when we talk about drug design. In practice this too is not that common because it's rare that that molecule will be able to first bind because it's not going to bind here, right? The shape is not correct. But what typically happens today is that you might have a molecule that kind of breeds, it undergoes a shape. So this molecule would sometimes have that circular interior and there is going to be some sort of equilibrium between that state and a state where the binding site looks different. And if I just happen to catch that molecule at a time when the binding site looks different then I might add my small molecule and have that small molecule then bind to the protein. And what then happens now I've locked the protein into that state and when the protein is locked into that state it's not going to go back to the first one. And this process we tend to call selected fits. This glutamate binding protein is actually an example of the last selected fits. You have a protein in the red and blue part here and the red and blue structures they really describe this called breathing motion of this small cavity. And so it can be either more closed or more open. But what suddenly happens if this one is in the right I think it's in the blue which is slightly denser conformation. If I happen to add a glutamate to the blue one I will really lock in the blue structure and then I'm going to stay in the blue structure. In this particular case we know that because we've been able to determine the crystal structures for both of them.