Sunday, January 17, 2016

January 18, 2016 at 01:23AM

Today I Learned: 1) ...so, yesterday I made the claim that the nuclear pore complex was the largest atomically-precise biological structure known to man. Turns out I was wrong. Very wrong. Mostly. The nuclear pore complex is about 120 nanometers in diameter, with a hole in the middle between 5 and 10 nanometers across (for scale, about 8,000 nuclear pores would fit across a typical period, and if a nuclear pore complex were scaled to the size of an american football, the actual channel would be a hole about a half-inch to an inch in diameter). That's pretty big. ...but not as big as titin. Titin is a protein used as a spring in muscles to confer their elasticity. It's a long, long chain that blobs up on itself; when stretched, the bonds holding the blobbing together break and it stretches into a long string. When tension is released, the protein folds itself back up into a blob, pulling the ends back in. Also, titin is absolutely freaking massive. Most proteins are a few hundred amino acids long. Titin is about *30,000* amino acids. Most proteins have mass measured in kilodaltons, or often tens of kilodaltons. Titin is just under *4 megadaltons*. Wikipedia helpfully informs me that the empirical chemical formula for titin is C169723°H270464°N45688°O52243°S912 (°s for clarity). Titin also has the longest technical name of any protein (for obvious reasons). From wiki: "The full chemical name of the human canonical form of titin, which starts methionyl... and ends ...isoleucine, contains 189,819 letters and is sometimes stated to be the longest word in the English language, or any language." That said, I'm not sure if you can call titin atomically precise. It's kind of floppy, and in fact flops around as part of its normal operation. Still, it has a more-or-less well-defined structure, and it's a heck of a lot bigger than the nuclear pore complex. 2) The US spends billions of dollars annually on fossil fuel energy. This worried me until I realized that a) it's only single-digit billions of dollars, which, while enough to show up as a blip in the US budget, only shows up as a blip in the US budget, and b) the US spends *more* billions of dollars annually on renewable energy. I thought for bit (hoped, really) that subsidies might explain why coal and natural gas are so much cheaper than the alternatives (though, that said, coal isn't as much cheaper as I remember it being), but then I crunched the numbers and realized that single-digit billions of dollars of subsidies annually, if they translated directly into customer savings, would still only provide a couple percent drop in price of coal energy. 3) Semi-rational protein design is way, way better than I thought it was. David Baker's lab at the University of Washington (one of the creaters of Rosetta and FoldIt@Home) have created a shocking number of proteins from scratch including: "Ideal" (regular, symmetric) globular proteins; protein helices held together with pair-specific hydrogen bonds, much like DNA but with three or more helices; proteins that form bundled fibers in various programmed configurations; small peptides that specifically bind to conserved flu coat protein motifs (and soon many other viruses)*; proteins that self-assemble into 2D space-filling lattices; sets of proteins that self-assemble into regular isocahedrons (d20s) of different, programmed sizes; and proteins that, when transcribed, can package their own RNA! Rosetta, the software that designs these proteins, starts with an empty tiny chain of amino acids, then iteratively tries adding different random amino acids, simulating the new chains' folding, and picking the ones that have the structure closest to the target structure. I'm guessing this takes quite a while to run, but it appears to be able to design proteins (and predict their structure) very, very accurately. One quirk of the software's design is that the proteins it makes tend to be extremely stable, to the point where some are essentially unable to be unfolded using standard techniques. * Apparently if you squirt these into ferrets and mice as an aerosol, it protects them against flu infection.

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