Thursday, August 16, 2007

Thursday is full of Meetings

PCBio for lunch and NSF for dinner. Which means I am up two free meals today. Which is pretty awesome. And they were fun, funny meetings too. Which is even more awesome. BUT since I had lunch and dinner at meetings, I am at work after dinner, which is less awesome. But it won't be too late, so that's more awesome again.

PCBio was full of projects I have trouble really getting into on their own merits: Computer modelling of protein folding, mapping energy surfaces for small molecules found mainly in the troposphere, and determining conditions for crystallizing proteins. So two out of three were certainly bio related, but in the very chemical-biology or computational-biology sense. But that's okay. Because the presenters were really good and got you to see the merits and excitement behind their projects, and Steve was in a great mood, actually, so it was absolutely hilarious.

I should really start taking notes, because there were a lot of absolutely hilarious things going on. But here are the few I remember, in the order I remember them and not the order they took place.

To the physical chemist (EmJ) who proclaimed, somewhat guiltily, "This project has zero relevance to biology, so I am not going to try to give it any," Steve responds: "That's a challenge."

Later in the same presentation, EmJ mentioned coal. Steve: "Where does coal come from?" It was followed by awkward silence, because everyone knew where it was going but no one really wanted it to go there. Finally someone responds that it's compressed oil, and Steve says that oil comes from compressed plants, and it's all well and good. He asks where the Sulfur in EmJ's molecule comes from, and got Methionine and Cystiene. "That's your biological relevance," Steve said. "The true meaning of plants, which is to eventually make fuel for our cars."

Later on in the same presentation, EmJ confides that her molecule is incredibly reactive, reacting even with the teflon that she used to coat her reaction vessels. She's going to try glass next. Maybe that will work better. Steve makes her flip back to an earlier slide which has a picture of her molecule on it, and asked why that molecule would react with teflon. There were a few people who answered seriously; Sulfur is particularly unstable with four bonds, etcetera, but the best answer is that MeOSOCl is "Smokin' hot." For the rest of the day, everything was "Smokin' hot." In fact, Julie decided that it was her new word. So "Smokin' hot" is "Smokin' hot."

Steve brought up the interesting idea that protein crystal structures do not, in fact, show a very accurate picture of that protein in action. In fact, NMR structures often have many equally valid solutions -- many different possible structures for one protein. Which is an interesting way to look at it; if a protein has multiple conformations that are valid, and in fact equivalent in terms of energies of atoms and the other things measured by NMR, a crystal will exclude those structures which are different -- thereby giving you a static picture of something which is actually dynamic. I'm sure that's not an actually particularly new opinion, but it is interesting nonetheless. There was a very funny dynamic when for about a minute or so Steve kept interrupting Alexander (the presenter for that bit) about random things and making witty remarks. I cannot replicate that exchange, but it was priceless.

I know there are other things, but I cannot remember them all today. Maybe next week I'll take notes. But if I bring things with which to take notes, it won't be as funny, I'm sure.

Oh well.


Duff said...

Doran brought that point up with me once, which has made me suspicious of protein crystallography ever since. You radically change the thermodynamic environment of the protein to perform crystallography, why wouldn't the structure under go all sorts of phase transitions? It is easy to come up with simply models that change radically with the environment they are in. Polymers, being not-simple, would seem to be even more susceptible to change.

Elizabeth said...

One interesting caveat to that is the concentration of protein in a cell. In fact, the concentration of protein in a cell is very similar to the concentration of protein in a crystal. Of course, the organization is different; but the amount of water and other ions is probably pretty comparable.

Something to keep in mind, that I did not know until I took an advanced biochemistry class.

Also, protein crystals are squishy. It's because they're really only 50% or so protein; the rest is water and stuff.

Duff said...

Ah, but temperature are they maintained at? That can be the clincher.

Elizabeth said...

Since I am not a crystallographer, I do not know for sure about X-ray temperatures. I think NMR is done at room temperature, and cryo-EM is of course done at very low temperatures. Also, my friends who do crystallography don't talk about needing to keep their trays at 37 degrees, so it might be a safe bet that most of the crystal formation is done at room temperature; which is about 12 degrees too low.