A molecular millisecond

By Brian Hayes

In the living cell, biological macromolecules do not sit immobile like bronze statues. They are machines with moving parts; they continually flex and wiggle, mesh and then disengage, spin, flap, bend, stretch; all day long they do a hyperkinetic hokey-pokey.

I have now seen a remarkable performance of that molecular dance. In a talk at Harvard earlier this week David E. Shaw showed two videos, each portraying about a millisecond in the life of a single protein molecule. A millisecond may not sound like much, but the video was created by computing atomic motions at roughly one step per femtosecond. That’s 1012 steps in all. (If you included all the steps in the video, and displayed them at 60 frames per second, the show would go on for 500 years.) …

Watching them in the lecture hall, I was so bedazzled that I neglected to note the identity of the molecules. One was an ion channel, a protein that spans the width of a membrane and controls the passage of some specific ion (potassium, I think, in this case). We watched the six polypeptide strands twisting closed like the blades of a camera iris, shutting off the channel. Another simulation showed an even more dramatic reconfiguration. For many microseconds of biological time, and perhaps half a minute of wall-clock time, the protein sat nervously quivering and fidgeting, hunched up in a compact globule, with occasional minor adjustments to various loops and corners. And then suddenly the whole molecule opened up like a flower blooming; a moment later it closed again. If I understand correctly what Shaw was telling us, the existence of this alternative state had been known from experimental evidence, but the transformation had never been seen before. And, as he remarked early in the talk, “seeing what it looks like” brings a level of understanding that would be hard to achieve by more analytic methods.