🚀 go-pugleaf

In article <2ut37o$h9a@tierra.santafe.ede> stadler@SantaFe.edu (Peter Stadler) writes:
  >We have been successfully folding 23S RNAs on an IBM RISC 6000/550
  >with 64MByte memory and the complete genome of the phage Qbeta on
  >an maschine with 256MByte. 

By successfully, do you mean "the computer didn't crash in a swap
storm", or "I got the right answers"? I suspect the first.  My advice
to someone wanting to fold a single molecule of 2.5 kb of RNA is
"don't do it". (If you have multiple RNAs, and you're using RNA
folding programs as a first-pass tool to help you look for a structure
they all share, that's a different story.) RNA folding programs
sometimes mis-predict 75 nt tRNA structures; I don't think I've seen
one ever get a 400nt group I intron right; and I don't even want to
think about a 2.5 kb molecule.

You can look at suboptimal foldings from Michael Zuker's algorithm and
say you succeeded because the presumed correct structure is within x%
of the global minimum, but you can only say that because you know the
correct structure (say, from comparative sequence analysis).  If
you're dealing with a new structure, how do you pick the correct guy
out of the haystack of suboptimals?

The level of faith in RNA secondary structure prediction is sometimes
shocking:

"The credibility of the resulting structures did not seem to be an
issue. There is even an unsubstantiated rumor (worth repeating) that
when Brosius, Noller, and their colleagues submitted the first 16S
rRNA sequence for publication, one of the reviewers questioned why
they had not included the molecule's secondary structure as well!"
             - Woese and Pace, in _The RNA World_, CSH Press, 1993

--
- Sean Eddy
- MRC Laboratory of Molecular Biology, Cambridge, England
- sre@mrc-lmb.cam.ac.uk