Phage attack:
the drilling begins
of the T4 bacteriophage
infection process and replication.”
Rossmann Laboratory and Seyet, LLC
I just watched an extraordinary set of videos that shows the assembly and operation of an intricate molecular machine. The Rossman Laboratory provided knowledge for these animations (titled “Accurate Scientific Visualizations
of the T4 bacteriophage infection process and replication”), and they used cryo-electron microscopy to get much of the structural data.
I’d like to thank Mehmet Sarikaya for sending me the link to these videos. I spent some time with Mehmet and his group last year at the University of Washington, where they are designing molecules that bind and help direct the growth of crystal structures. We discussed how Nanorex could develop computational tools to help with this work. Results in this area of research could play an important role in fabricating precise, inorganic components for composite nanosystems. More on this later.
The videos lie because they must
A warning about the videos, however, and about every similar video I’ve seen that depicts biomolecular assembly and function: They lie about how biomolecular machines move. Where they show smooth, purposeful-looking mechanical movement, the reality is instead a frenetic dance of Brownian motion.
Biomolecular machine components thrash aimlessly to and fro, battered by water molecules, until they happen to hit a position where parts click into place, thereby advancing the machine by a single step. This process occurs in every molecular step taken by the machines that pull the fibers that contract the muscles that move your arm.
Likewise, during self-assembly, molecules don’t fly toward their destinations and dock smoothly; they tumble and vibrate and wander in all directions, traveling enormously long and convoluted paths before they happen to find a place where they fit, bind, and remain.
The videos lie because they must. The Brownian motions of biomolecules occur on a microsecond time scale, yet the net result — advancing a machine or assembling a part — takes milliseconds to seconds. A video that showed the true motion would either
- be a thousand (or a million) times as long, showing tedious sequences of aimless activity, or
- would show each moving molecule as a wide, fuzzy blur that instantaneously condenses into its binding site.
Instead, the videos show a kind of smoothed result, in which parts move into place as if driven by non-existent machines even smaller than themselves.
So there’s a good reason for the lie, but I’d still like to see at least one fully realistic video that contrasts the simplification and the reality. Other videos could lie a bit less by showing paths that wander a bit more.
Even with this caveat, the videos are wonderful, and almost everyone can learn something from them.
About the videos of genuinely machine-like machines…
This is a final, surprising twist to this story: Physics-based simulation and analysis show that nanomachines made of stiff materials really can move like conventional machines, with Brownian fluctuations causing only low-amplitude vibrations around purposeful, mechanical paths. (But there’s still a problem with the depiction of Brownian motions in most of the videos — beware of the Stroboscopic Illusion!).
To make machines like these will require tools and techniques that have not yet been developed, and developing them will require many steps. There are paths forward and Mehmet’s work is helping to pave the way.
{ 4 trackbacks }
{ 6 comments… read them below or add one }
Drew Whitehouse 01.12.09 at 11:33 pm UTC
Take a look at Drew Berry’s work, he uses procedural animation techniques to allude to the brownian motion.
Chris Phoenix 01.13.09 at 8:07 am UTC
It’s worth noting that the machine-like nanostructures built of 3D covalent solids … ah, heck with political correctness – “diamondoid” machines … such as the gears shown in the Nanorex videos, some of which are actually made of (simulated) diamond…
OK. According to simulation, small diamondoid machines should be able to operate at GHz frequencies, as opposed to the kHz or MHz frequencies of biomolecules. (Of course, they’d have to work in vacuum to avoid fluid drag, but they could still use a surprising range of biomemetic physics tricks.)
It may also be worth noting that the “microsecond time scale” you mentioned for biomolecule Brownian motion is for whole molecules making molecule-scale motions. Thermal vibration of atoms happens much faster – THz to PHz, IIRC. So a video of a gear turning at 1 GHz and showing individual atoms *still* won’t show thermal motion. (The surface of a diamondoid gear will deform by far less than an atomic diameter, so an animation (such as the Burch/Drexler animation) that shows mainly smoothed surfaces can be considered largely accurate.)
Chris
Tshepang Lekhonkhobe 01.13.09 at 11:46 am UTC
Reading this reminds me of Unbounding the Future (1991) where there’s a picture of one getting immersed in virtual reality and ‘experience’ the functioning of matter at molecular level, where various things a tuned to lie since the environment would otherwise be too violent to be bearable.
What I’ve for a long time wondered of is if that book is still recommended after all this time. There’s much that’s beautiful in it, but nobody seems ever to mention it. Did it lose its relevancy?
Will Ware 02.08.09 at 6:16 pm UTC
Unbounding the Future was definitely a great book and it doesn’t get as much credit as I think it deserves. That simulation scenario in the second chapter was great.
The third video of the T4 assembly is a beautiful piece of work but it worries me. We’ll want to engineer protein-based machinery, and viruses will be at the low end of the complexity scale we want to work with. Look how complicated even just a T4 virus is — there are a dozen or more protein species involved, fitting together in complicated ways, with hundreds of copies involved. The design and simulation task to design a new virus would be large. The simulation resources exist in the pharmaceutical industry, but perhaps not elsewhere.
If the pharma industry develops protein machines, all the knowledge will be under patents and other IP protections, and the products will be expensive to the end user. If we can find the necessary simulation resources in academia, there won’t be much profit motive to incentivize development. It would be good to see the rapid development that’ s possible in a closed-source commercial world combined with the openness of an open-source world, but it’s not clear how that would be funded.
Eric Drexler 02.09.09 at 1:44 am UTC
@ Will Ware — It’s important to keep in mind that when researchers design proteins and self-assembled structures (including the structural DNA nanotechnology work, of course), they design parts that will bind together properly, but don’t directly consider how the parts will move around before coming together. This means that there isn’t any use of dynamical simulation.
In the case of DNA structures, the design is guided by the desired geometry of the product, and the binding is assured simply by Watson-Crick pairing. You know this, of course, since it’s what we worked on together at Nanorex, but the principle generalizes to messier problems like the design of protein folds and protein-protein interfaces. Here, computational tools must do a lot more work, but the work consists of searching a combinatorial space of amino-acid sequences and geometry tweaks, all with reference to static structures and meeting design objectives for the intended product.
———————
In this connection, readers with spare machine cycles might want to look at Rosetta@Home; readers with spare brain cycles might want to look at and FoldIt. I’ve enjoyed both, and the Baker Lab is doing state-of-the-art work
XiXiDu 02.07.10 at 11:51 am UTC
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.)
Shaw was once a computer scientist at Columbia, then he went off to make some billions on Wall Street. (He was introduced to the Harvard audience as “King Quant.”) He has now turned to computational molecular biology, setting up his own lab and building a series of special-purpose computers designed for molecular-dynamics simulations. The machines are called Anton, in honor of Leeuwenhoek. Shaw’s group has built eight of them so far, each with 512 processors. A kiloprocessor model is expected to come on line in a few weeks.
http://bit-player.org/2010/a-molecular-millisecond