Today and tomorrow, we're reporting on presentations at an important conference on Productive Nanosystems: Launching the Technology Roadmap. Chris Phoenix is providing live blog coverage for us...
Second talk Tuesday: Chris Schafmeister: got started in protein design, designed a protein--which took four years. He would like to make things like proteins and enzymes, but rather than building flexible chains that have to fold, he wants building blocks that couple through (rigid) pairs of bonds. Since they don't have to fold, they will be easier to design. The building blocks can be "decorated" with functional groups to make enzyme-like things.
Productive nanosystem definition: "A closed loop of nanoscale components that make nanoscale components."
Schafmeister has built 14 building blocks - some of them, they can make tens of grams at a time. They've built one with a functional group and they're working on other functional groups - some not found in natural amino acids.
They attach a building block to a plastic bead, then add other building blocks one at a time. This is not self-assembly: it is programmed assembly. They want to build molecules containing 20-50 blocks. That's a lot of reaction steps! Once they've built a chain, they double-link it, making it rigid. They've synthesized over 100 molecules; most are very water-soluble; the most building blocks so far is 18.
He's got an 8-page featured article in "Scientific American Reports: The Rise of Nanotech."
He wants to "create many artificial catalysts that approach the capabilities of enzymes." No one has made an enzyme yet - he wants to make thousands of them, engineered. He wants to make 60,000 enzymes as rapidly as he can write 60,000 lines of code. This may be achievable because enzymes carry out catalysis (accelerating chemical reactions) by changing the mechanism of the reaction. It does this via functional groups arrayed around the substrate. "If we can position multiple functional groups in three-dimensional space in all the right places," then we may be able to implement enzymes. So if functional groups (found in databases) were positioned in space correctly, you'd have the enzyme.
So, figure out where the functional groups should be, then use computer search to find the sequence of building blocks that holds the functional groups in the right position. He shows an example of his software working, searching for a sequence.
Proposes a "nanomachine synthesizer": 1) Chemical solution vat 2) Personal computer 3) Electrochemical interface. In biology, DNA is transcribed into messenger RNA, the sequence of bases which are read into the sequence of proteins. Trouble is, there's no place to plug in a computer. So replace the DNA with a computer...
He proposes a "synthesis train" - a sequence of carriers (built of his molecules) each of which carries one building block. So he'd build the synthesis train out of his molecular building blocks, and the train would then carry other building blocks to build other molecules. The carriers would be rigid, and when the chain was bent, it would bring the building blocks together and make them react. The building blocks would be put onto the train, and error-checked, by yet other catalytic molecules.
Electrode chips exist which act as redox controllers and sensors, driving chemistry with electricity. He wants to use similar electrodes to modify his synthesis trains. Each train has a header with a switchable state. So you start with a bunch of one-"car" trains (one "header" plus one car), then string the "cars" together onto a single header.
He wants to have a system that can take in very small feedstock molecules, build building blocks, then put them into chains under full computer control: massively parallel.
Once he's built 50-block chains, to put them together into larger structures, he wants to do it with covalent bonding rather than self-assembly. Stronger and potentially more reliable than self-assembly.
To design something like a biomedical robot: First, design each component and how they will fit. This is a huge job. Break it down into components and sub-components. Design the smallest sub-components with complementary surfaces... then design the catalysts that will combine the units... so you're building both structural chains and catalysts to join them. You probably couldn't build a car with this, but you could build things large enough to see and handle. Again, this is not self-assembly. He has some ideas for how to build things that are too big for chemical reactions. He skipped past some very interesting slides showing probe tips used to place molecules.
His summary: This builds on biology and organic synthesis experience. There are opportunities for error correction as needed. It's highly parallel and highly redundant. There's no runaway self-replication. You can improve it incrementally.
Question: How long do the chemical operations take? A: Seconds, maybe minutes. Not hours. Right now, we do one per hour (10^17 molecular copies).
Question: In enzymes, moving the active site even a few angstroms can break the enzyme. So you may have trouble positioning your active components precisely enough. A: I get this question a lot. The search space is enormous: 14^30 three-dimensional structures. The molecules are not completely rigid. The goal is to be off by less than a couple of angstroms. Also, the functional side chains will have free rotation; we'll either have to block that, or see if we can use it. In natural proteins, when you add a substrate, the protein folds up around it.
Q: Have you looked at branched structures? A: There aren't enough protecting groups in chemistry. (So you couldn't build out each chain separately.)
So... this sounds like a very aggressive and interesting way to build large molecule systems which can be designed to be functional.
Chris Phoenix
Tags: nanotechnology nanotech nano science technology ethics weblog blog
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