Ebola puzzle 1000
We've been quiet about Ebola for a while. I just wanted to let folks know that we have gone over the results from Puzzle 1000, and players have produced some very promising starting points for design. In particular, the top-scoring solution, which came from the GoScience team, has a couple of hydrophobic amino acid residues providing very nice shape-complementarity to the binding pocket, and also happens to form a nice beta-hairpin (with a couple of good backbone hydrogen-bonds) that can serve as a great starting point for further design. The GoScience design is shown in purple in the cross-section below, with the Ebola glycoprotein in green.
The second-place team, the Contenders, also filled the pocket quite well, using two aliphatic amino acid side-chains rather than an aliphatic and an aromatic. This also was in a hairpin conformation. The fact that players were hitting on a consistent backbone conformation over and over also helps us: it tells us that this is the backbone conformation that tends to fit here, narrowing our search.
There were a number of other interesting designs, too, even though some weren't the top-scoring. L'Alliance Francophone, for example, created a good design that filled the cavity well while simultaneously forming some good hydrogen bonds between the target and the peptide. Please continue to share your most interesting designs with the scientists, whether or not they're the top-scoring!( Posted by v_mulligan 80 1779 | Thu, 01/15/2015 - 21:49 | 6 comments )