Scientist Feedback on the Hotspot Finding Puzzles

Started by v_mulligan

v_mulligan Lv 1

     Hi, folks. I just wanted to write a quick note thanking everyone who has been playing the hotspot finding puzzles. Players produced some very neat designs in both the SOD1 and Ebola puzzles. The Ebola one particularly has yielded some great starting points for design, and we currently are extending players' designs using Rosetta to try to make peptides and proteins that neutralize the Ebola virus. I was also very interested to see common features emerging in the diverse designs. Many players seemed to find, independently, that there was a "shelf" in the Ebola glycoprotein that could accept an amino acid with a flat side-chain, and that this was was adjacent to a "chasm" that could accommodate something with a long side chain. These players created designs accordingly with many different "shelf/chasm"-filling pairs. This is the sort of insight that only human intuition can provide. Automated algorithms have a very hard time discovering patterns like this.

     Thanks also to those who have been using the "share with scientist" button. In both puzzles, there were some very interesting designs that were shared. I noticed that in the SOD1 puzzle, a few clever players noticed the two cysteines (cysteine 111) located on opposite sides of the dimer interface, and created peptides with two cysteines that could form disulfide bonds to both of these amino acids, thus covalently linking the dimer. These designs weren't the highest-scoring (the scoring function isn't smart enough to recognize this as a good design), but they're definitely useful designs, and they're exactly the sort of thing that the scientists want to see. Good idea, and good work!

     We've got a lot more targets for which we need hotspots, so if players are enjoying these puzzles, we can post more. Feedback on this hotspot-finding puzzle format is welcome, too. It's our hope that these puzzles will give us the starting point that we need in order to allow us to design drugs to treat some very nasty diseases, so your participation is greatly appreciated.

          –Vikram K. Mulligan

v_mulligan Lv 1

I find it interesting that you say that this was a difficult puzzle – that's the sort of player feedback that's quite useful. What was it about this puzzle that made it more difficult than usual? Can you think of anything that we could change about the puzzle format that would make it easier?

AsDawnBreaks Lv 1

Heh, not at all! The difficult part is that there's very little to do. You have 3 segs, and you move it around. However, I ran gab bis flu, which adds random bands around the ligand, and it got higher scores pulling it out of the pocket… Found that rather odd.

karstenw Lv 1

i find these puzzles hard too. i just haven't found a good strategy for this. i think if lots of players try these puzzles then maybe we could stumble on something good. they are tiny enough that we could get lucky, plus some players are pretty good at jamming those boogers right on in there.

wisky Lv 1

I'm with kars.

Bring. Them. On.

Though I don't think we need 12 days for a puzzle with only 3 mutable residues…

spmm Lv 1

I find these difficult, my first try is usually the best, but the main problem is that they are so big and resource hungry, if you could trim them even more, players might attempt them for longer and more often. Appreciate that is not easy to do.