Comment by kanzure | Hacker News Reader

Comment by kanzure | Hacker News Reader

One of the startups that fizzled out was Nanorex, which is where Nanoengineer was made. Thankfully they were open to releasing the source code and version control repository when they decided to shutdown. The results of that are here: https://github.com/kanzure/nanoengineer

I think everyone is stuck wondering how to make the tooltips from the tooltips paper: http://diyhpl.us/~bryan/papers2/nanotech/Optimal%20tooltip%2...

All of that was motivated by goals of making nanofactories like shown in this eye candy video: http://www.youtube.com/watch?v=vEYN18d7gHg

Because positional, precise molecular manufacturing still doesn't exist, I have been increasingly interested in using DNA synthesis (using phosphoramidite chemistry) to combinatorially build proteins that lock together in pre-defined shape based on ligand-specific binding affinities between the blocks. The Nanosystems book left out a lot of biology that can be hijacked to help out goals like these.

Long-term we might be able to coerce enzymes into creating molecular machines anyway: https://groups.google.com/group/enzymaticsynthesis

Our lab is working on ways to screen large libraries of designed proteins for engineered orthogonally interacting libraries. The thought would this would be a start of a modular resuasable library for molecular self-assembly. If you are interested, we're definitely hiring!

Yeah I really enjoyed your 2014 review of large-scale DNA synthesis techniques. I have been funding a project similar to POSAM except instead of DNA hybridization arrays the goal is genome synthesis. Basic summary is use inkjet printheads which can print 100s of millions of drops per second.

I also blatantly steal your diagram on the following page, so fair warning.

http://diyhpl.us/wiki/dna/synthesis/notes/

Oh interesting. We should definitely talk at some point. You in LA anytime soon?

As I see it, proteins are our best bet of making custom nanomachines. They're proven to work. The hard part is understanding protein folding and predicting protein function from the amino acid sequence.

Ideally we can find a way to engineer proteins that have known shape and conformations and binding, without having to increase our knowledge about protein folding or DNA folding. Maybe certain amino acids fold more heuristically-predictably than other amino acids? And ligand binding affinity is much simpler to engineer compared to the computationally expensive molecular dynamics simulation of protein folding. There's probably other options here, too.

There is the fact that proteins are constrained to function as part of organisms that are capable of self-replication. This constraint means that proteins (mostly) are not very stable wrt oxidisation and UV degradation, and only work properly in aqueous solution.

It's anyone's guess how significant these constraints will be from the viewpoint of developing artificial protein machines (maybe rapid (bio)degradation is a good thing!), but there's definitely large swathes of chemical design space outside of arbitrary chains of known amino acids, and we might be able to discover entire classes of molecular machines that don't have the drawbacks of bioinspired proteins.

Probably. But to do that, we need to be able to do work on that level; existing proteins seem to be just about enough for us to run proper experiments and eventually bootstrap production of nanocomponents better suited for our needs.

All of that was motivated by goals of making nanofactories

I wonder how we can hope to make nanofactories, when we don't even have a robot arm that can fold my laundry for me.

Laundroid claims to do just that: http://www.telegraph.co.uk/news/worldnews/asia/japan/1192259...

We had such arms for decades already. Just because nobody bothered to make a laundry folding product out of them doesn't mean we can't do it with a robot arm. For better or worse, many (if not most) interesting projects aren't viable as business products.

The arm is not the hard part. That is why this doesn't exist.

It is entirely possible http://www.youtube.com/watch?v=gy5g33S0Gzo , but there is no market for a domestic robot. Not even for an AiBo.

You see: poor people are accustomed to doing these chores by themselves, while the rich can always use their paper money to hire naturally occurring biological robots.

It's crazy to think about that molecular nanoassembly was the position that evolution started out from.

Yeah I guess that is pretty crazy. OTOH, there was a study of a virtual machine where someone filled RAM up with random opcodes and running the machine forward in time brought about self-replicating programs because of random self-copying sequences of opcodes. So maybe self-replication is simpler than we've been making it out to be?

http://diyhpl.us/~bryan/papers2/ai/The%20evolution%20of%20se...

(To be clear, the first "self-copying sequences" didn't look like self-replication in CoreWars or whatever, but evidently they did observe the construction of self-replicating programs over time.)

Thomas S. Ray's Tierra is a very similar study, published already in 1991.

https://en.wikipedia.org/wiki/Tierra_%28computer_simulation%...

Tierra was interesting, but these days I would point anyone interested in that direction instead at Avida and BEACON.

https://en.wikipedia.org/wiki/Avida

http://beacon-center.org/welcome/

In particular this was a surprisingly interesting overview of their recent work:

http://beacon-center.org/wp-content/uploads/2014/10/BEACON20...

Don't also forget Conway's Game of Life.

Doesn't nature have a lot of inherent stochasticity down at the molecular level that makes it very difficult to do positional, precise molecular manufacturing, due to everything jittering around randomly?

Correct, but you can still get binding-specific behavior:

https://www.youtube.com/watch?v=Ms_ehUVvKKk

https://www.youtube.com/watch?v=q_n0Ij3K_Ho

https://www.youtube.com/watch?v=Jml8CFBWcDs

Well if you have stiff enough molecules, then the distance a given molecular structure moves due to thermal fluctuations can be smaller than an angstrom. In addition, if one cools said system down, thermal fluctuations become less of a problem.

Actually assembling individual atoms together to make stuff is still very much an unsolved problem. Freitas' work on mechanosynthesis tooltips shows that we may need to control more than just position to precisely react atoms and that 'fat fingers' is still very much a problem.

The ribosome, DNA replication complex and ATP-synthase (and other complex enzymes) qualify as precise molecular manufacturing, if you relax the definition a little. Ribosomes are already being engineered, see expanded genetic code.

How far could we go by modifying existing biological molecular machines? Probably quite far.

That's true, but those all work precisely by taking advantage of thermodynamic jitter to get things done.

Bryan, were you involved with Nanorex?

Nope, I wasn't involved with Nanorex, just the recovery of the files and then "maintaining" the software ever since I learned about the company's imminent death.

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