This puzzle starts with an unfolded sequence with secondary structure assigned from PSIPRED. The target protein is LepB and is currently being investigated for drug discovery against Tuberculosis (TB). TB is caused by the bacillus Mycobacterium tuberculosis and has killed more than 1.5 million people in 2014. Right now, no crystal structure exists for this target. Models created by Foldit players will be used to help solve the structure when crystals become available.
With the discussion here, we could start some new designs (jeff101 said he would do).
The top scores seem very low for such a long puzzle.
With also the holiday period, this could be an argument to extend the deadline a little bit (2 days?).
"The phylogenetic position of Mycobacterium tuberculosis relative to other bacteria is controversial. Its cell wall has characteristics of both Gram-positive and Gram-negative bacteria. In the standard reference of bacterial phylogeny based on 16S ribosomal RNA sequence comparison, M. tuberculosis belongs to the high G+C Gram-positive bacteria that form a monophyletic group with the low G+C Gram-positive bacteria such as Bacillus subtilis. Some analyses indicate no particular relationship between these two groups. The availability of the complete genome sequence of M. tuberculosis allows us to reexamine this issue from genomic perspectives, as genome-based phylogenies may be more representative of the evolutionary history of whole organisms than molecular trees. In the genome tree constructed based on conserved gene content, M. tuberculosis is more related to Gram-negative than to Gram-positive bacteria as reflected by the evolutionary distance between nearest ancestral units. This conclusion may be supported by another analysis showing that M. tuberculosis shares relatively more orthologous genes for energy production and conversion with Gram-negative bacteria, in particular, Escherichia coli and Pseudomonas aeruginosa, than with Gram-positive bacteria" (Fu et al, 2002)
Fu, L. M.; Fu-Liu, C. S. (2002-01-01). "<a href=http://www.ncbi.nlm.nih.gov/pubmed/12356459">Is Mycobacterium tuberculosis a closer relative to Gram-positive or Gram-negative bacterial pathogens?</a>". Tuberculosis (Edinburgh, Scotland) 82 (2-3): 85–90.
Thanks to Jeff for the combination calculations. I think my head hurts thinking of the combinations. My probability course predated calculators and consisted of a little yellow pamphlet of about 30 pages, and for statistics we used a book of tables to look things up in case our estimating skills had us look at the wrong band of the slide rule. I graduated college undergraduate with a math minor and without a calculator as they were still too expensive, even for the professors.
And thanks to Susume for her insights into where the binding pocket for the catalyst might be (as well as JMBrownlee) I don't think any of this fixes my fold for TB :D But it makes me feel better about having to do what I could with the little time I had this week. I would love a redo of the TB puzzle with more direction and enough time for those of us with slow computers to fold a solid start. I'll pass a few smaller puzzles up so long as it is not an ED and doesn't require trying to learn to read anything in stick mode. All I know is what I have is likely of little use to science. And knowing why would be immensely useful to me
Skippy