 The only somewhat irritating part is that I keep hand waving, but we do not need to hand wave. One advantage today is that we have computer simulations. We can actually look exactly at what happens to specific helix and specific residues inside a membrane. And I'll show you a movie of that, that one of my students Anna Johansson did many years ago. This is of course a highly simplified system and I'm only showing one helix and then we're zooming in and making the lipids transparent here. This particular helix is mostly hydrophobic, but there is one residue here that is not. Not only is it not hydrophobic, it's even polar. This is a lysine sidechain, I always get busy from this movie, sorry. This lysine sidechain is at the end of the helix, so and being at the end of the helix, do you see where the lysine ends up? Well, the lysine is not really in the membrane. Technically, it's a residue in a transmembrane helix, but the lysine sidechain itself is very happy up here in the head group region and even the waters. Those dotted yellow lines you're seeing here are hydrogen bonds that it's forming, not even hydrogen bonds. We tend to call them salt bridges when they are with a charged region. So all those charges in lysines located this far up will be paired. So we're not going to have that poor lysine sitting in the membrane all by itself. That one was quite happy. So don't assume that the second you see a charged residue in a helix means that it can't go in a membrane. It will matter where we put it in the helix apparently. A better way of showing you this could be this. This is a helix. I think there were some lysines in this, but I don't show them. In general what a helix can do, this central part here I cannot have any water in. But if there are some slightly hydrophobic, hydrophilic residues here, at least at the end I can distort the system a little bit to pull in a bit of water here. That is not good per se. On the contrary it's bad per se. But it's better to put a little bit of water here to make sure we at least have some hydrogen bonds rather than taking say a polar residue and pull it into a completely hydrophobic environment. A little bit of distortion is better than having unpaired charges or hydrogen bonds. So what happens though if we take that lysine that I had before and try to pull it further down in the membrane. I have a movie of that.