Gazing at the very first model of a protein structure determined by X-ray crystallography Max Perutz, one of the founding fathers of the technique, was disappointed. It may have gone unspoken at the time but the initial coiled, worm-shaped creation resembled nothing so much as a giant turd. “Could the search for ultimate truth really have revealed so hideous and visceral-looking an object?” lamented Perutz.
Polished, but still ugly? (From London’s Science Museum)
But that early dismay was soon forgotten. The first model of myoglobin, an oxygen-storage molecule from the muscles of sperm whales, was based on relatively low resolution data and revealed only the overall fold of the protein polypeptide. As crystallographers worked their crystals, getting them to scatter X-rays at higher and higher angles, the atomic details of the molecular structure were soon revealed. The consternation at the irregularity, the lack of symmetry in proteins—where was the slender elegance to mirror DNA’s double helix?—soon evaporated before the glittering galaxy of atoms and bonds.
Which brings me to a wet weekend in Hamburg. Last weekend in fact when I found myself at the synchrotron, along with two members of my group, peering into a microscope at three O’Clock in the morning and trying to fish out tiny protein crystals with a miniscule loop of nylon attached to the end of a metal pin. Well, they weren’t that miniscule by modern standards; in fact the crystals were rather chunky—about 0.3 mm on each side.
Once caught, the crystal was placed in the direct line of fire of an intense X-ray beam. We retreated from the lead-lined experimental hutch and instructed the computer to open the shutter.
And when we did so, our mouths dropped open too: the crystal diffracted to 1.4 Å! In the lab it had only gone to 2.7. We were hoping to do better than that at the synchrotron but 1.4 took our expectations and booted them out of the stadium. What can I say? We were very pleased!
And why exactly? What do these numbers mean? It tells you how much detail you can expect to see in your electron density maps, the three-dimensional chicken-wire that we compute from the data to reveal the shape of our molecule.
And I have just this afternoon gazed upon the electron density map. And now you can see it too. It still looks like worms but this time they are knurled and knobbly; you can just about see that the molecule is constructed of tiny spheres. Atoms. In places, even the hydrogen atoms, each with just a single electron, can be seen protruding shyly from the density. In all my time as a crystallographer I have never seen a molecule in such glorious detail, and neither has anyone else in the lab. So today everyone is wandering around with smiles on their faces. And nobody is mentioning poo.
Coda: This morning, although I (gently!) mocked Richard’s heroic attempt to generate a buzz around science by encouraging people to post in something like real time as they did their experiments, I guess I have endeavoured to capture something of the immediacy of a real result in this post. So I’m a hypocrite. So sue me.