From: ian@inf.ethz.ch (Ian)
Newsgroups: sci.nanotech
Subject: Re: photoribosome
Date: 8 Sep 92 19:46:42 GMT
Organization: Dept. Biochemistry, University of Bristol, UK

In article <Sep.2.16.52.01.1992.14146@planchet.rutgers.edu> keithl@klic.rain.com (Keith Lofstrom) writes:

>What if one bonded a relatively small molecule on the end of a rhodopsin, and
>bolted the whole thing onto the read end of a ribosome?  The little molecule
>has sites that resemble to a ribosome the different bases it sees when it 
>reads
>an RNA, with the sites arranged in a ring.   The little molecule also has some
>sort of mechanism to start and stop the ribosome from travelling down it.  It
>has two simple commands - rotate (select) to the next site, and activate
>ribosome to read that site.  These commands are received optically.


<Coloured Light Coding System Deleted>

There are a number of problems with this system:
  i) Ribosomes read bases in triplets (codons) not single bases.  There are 21
     different meanings for a codon.  This doesn't effect the meat of your
     scheme but it does make the 'small molecule' (lets call it a pseudo-
     template) quite large.  63 bases if we don't do anything clever like
     trying to overlap the codons.

  ii) The RNA is not at one end of the ridosome, but rather runs through
      a hole in the middle (I think that's right, damn I'm forgetting my own
      subject, it's certainly at least a deep groove).  Which will make it
      difficult for the ribosome to accomodate our modified (and inevitably
      enlarged) pseudo-template.

  iii) One of the things a ribosome has specifically evolved to do is to read
       the RNA template in a sequential fashion, I don't think it would be at
       all easy to force it to allow the pseudo template to skip codons.  The
       basis of this is that the ribosome has two adjacent codons located at
       sites within itself at any one time and the assembly of the protein
       procedes through a stage in which both codons are simultaneously bound
       to tRNA (tRNA molecules are handles by which the ribosome handles
       the Amino-Acids; they have an Anti-Codon at one end which recognises the
       codons on the template).

<Description of use of system deleted>

>I can imagine that this setup could be used to put together proteins at very
>high rates, limited only by the ability of the solution to dissipate heat from
>all the wasted photons.  The pieces of the modified ribosome could be
>laboriously put together with traditional wet chemistry and biological
>techniques;  in most cases we are working with "found" materials.

It would be limited by the speed at which ribosomes operate, about 1 protein
per minute.

>This little beast could be optically programmed to build "second stage"
>ribosomes - modified ribosomes with the functionality built in rather than
>mixed together.  THOSE ribosomes could, in turn, be used to crank out 
>assemblers.  This is all predicated on a lot of protein design computation
>by macroscopic computers which we don't know how to do yet, of course.  In
>a very hand-waving way, this could be a path to implementation - once we learn
>what to implement.

We already have a way to build second stage ribosomes, standard genetic
engineering !  What we don't have (as you admit) is the design of a second
stage ribosome, a far, far harder problem to overcome.

>Well folks?  Whaddaya think?

I think, I'm very glad to see a little lateral thinking about how to implement
nanotech.  I also think this idea is, as you intended it an interesting start
point for discussion.  But I think the idea itself is a little too flawed as it
stands and needs a rethinking.

An idea I foind more promising is the prospect of extending the genetic code.
This can be done by taking one of the Amino-Acids which is currently covered
by more that one codon and subverting the spare codon to mean an unnatural
amino-acid of some kind.

Ultimately this could be done by redesigning the acyl-tRNA synthetase (the 
which bonds the right amino-acid to the right tRNA) but for the time-being
it could be achieved by using chemistry to achieve the same reaction (I think
this was in fact done years ago as part of the elucidation of the mechanism of
protein synthesis when it was shown that if a tRNA was attached to the wrong 
amino-acid, the ribosome wasn't able to tell and incorporated it as if it were
right.)