 Can I predict what parts will face the membrane versus what parts will face the interior? That was a really good question when we first started seeing structures. So the first protein structures, we thought that they should be the opposite of globular ones. That's not true. Membrane proteins are, to first approximation, hydrophobic everywhere. The only weak signal we have is that we can look at information contents in bioinformatics. What is information contents? Well, that means that if I have a protein and I look at many sequence alignments, there will be some patterns here that residues exposed on the surface here will change more quickly while residues that are buried are going to be more conserved. The reason for that is simply if I have an alanine here, it's going to be very unlikely that I can replace that for a tryptophan. But if I'm doing it exposed on the surface here, it might be possible. So there is a clear signal that the buried residues have more information when looking at sequences while they're fully exposed ones have less so. If there's one thing you should remember here, it's that membrane proteins are not simply globular proteins that are oriented inside out. They are hydrophobic everywhere, which makes them beautiful, but also very difficult to understand because it's going to be hydrophobic packing everywhere. So if it's hydrophobic everywhere, can't we say anything about the rest of the user card? Of course we can. Based on all the things that we've gone through, you now know that small aliphatic linear hydrocarbons, if they are hydrophobic, they will primarily be on the inside hydrophobic part. Charged residues, they will primarily be facing water. In this interface region, all bets are kind of off. The one thing that we can say is most common to see aromatic residues here, but the patterns will serve you very well. You should just be aware that there are exceptions to them. Gunnar will later tell you about the positive inside rule. I'm not going to go through that in detail, but if you for a second buy that they're going to be more positive residues on the inside and more negative on the outside, we can calculate that statistics from the protein data bank. This is over 10 years old results, and we definitely see that trend, but then we can subtract the overall trend, the difference between positive and negative ones, and see once we've removed that, where do they occur? And then you see a pretty fun peak that you have. It's not entirely easy to see here, but you have an excess concentration of these charged amino acids, both charges in the head group regions. So charges actually prefer to interact with the head group regions over water, partly because there are so many other charges in the head group regions. The lipid head groups are more charged than the water molecules.