 So why does a protein unfold? Well, for the same reason that it folds with just a minus sign in front of it You know the equation that governs this, right? It's going to be delta G equals delta H minus T Delta S, but we have to think of the signs. Now I'm starting from my nice stable folded states and moving to the unfolded state Which is the opposite as when I was moving from water to oil What does this mean? Well Delta H is usually going to be positive because I lose interactions when I unfold my protein and as the temperature goes up that effect is actually worse Delta S on the other hand that is usually going to contribute to the other direction The most chains have more entropy when they're unfolded. So that's going to compensate But as the temperature goes up that effect becomes less pronounced simply because both the folded and the unfolded states are relatively disordered The interesting part though is that the net balance here comes out to a relatively small difference Let's look at that in terms of protein folding. So this would essentially be the curve I showed you in the lecture three, but now it's upside down The important part here is the red curve and then we've split things out into polar and non-polar atoms enthalpy and entropy There's going to be a fairly narrow regime here where the black curve delta G is positive And what that literally means is that in that temperature regime I would have to pay free energy to unfold the protein aka the protein is stable But as the temperature increases roughly from here and up I'm going to gain free energy by unfolding the protein meaning that the protein is not stable It's also a very flat curve compared to the individual components, but you see the left part It's almost it is going below zero down there So just looking at that curve This would basically say that at low enough temperatures protein would also unfold. We've never seen that But let's look at a few proteins So here are a bunch of them. Do you see the shape of the curves? We start out here, and then the curves comes down here, and then they all start to turn down here This is remarkably stupid. Why on earth didn't the researchers just continue the curves down here? Well, these are proteins in water and there is a very special thing that happens to waters at zero degrees centigrade So the problem is water freezes, and then we're not really going to see that But since we want to see the end of the movie There are cases where you could for instance mix some salt in the water or study proteins where this transitions happens slightly higher There are a bunch of researchers that have done this and here's a Swedish group that did it a few years ago The point is that there is cold and aturational proteins and we can see it Due to the temperatures happening at freezing point. It's harder, but it's definitely possible to do in a whole lot of cases So proteins are only stable in a fairly narrow temperature regime Make it hotter at the unfold make it colder, and they will also unfold But that can't really be interesting right because in practice this would only happen at temperatures below zero degrees centigrade. Well Can you imagine any creatures living in areas where you would actually be subject to temperatures below zero degrees centigrade? There are for instance fish in the Antarctic And they live at around zero degrees centigrade. It can even become freezing. The reason why it doesn't freeze of course is the salt in the water What these organisms tend to do is that they express lots of cold shock proteins and you might even do that too Many of us do that if we are to protect our DNA replication system and everything from unfolding If an organism is subject to very cold conditions It might start to express these proteins whose job it basically is to protect other proteins from unfolding There are heat shock proteins too and this that's actually happens in a few cases For instance animals that live in hot springs or so where it's 70 or 80 degrees Then of course animals that live under these conditions for a long term They tend to evolve their proteins so that the proteins are either stable at much higher temperatures than normally required or stable at lower temperatures What you could ask yourself finally said wouldn't it make sense to overall make proteins more stable so you didn't have to suffer through this lecture in particular The problem is that at some point you need to degrade proteins to actually you're degrading them all the time In your stomach and if proteins were too stable it would require huge amounts of energy Once we need to dispose of the proteins so we want proteins to be stable, but they should only be stable enough Not ten times more than we need to