Competition results for influenza HA binder design

[nspc]

Foldit is more a cooperative game that a competitive one.
The goal was to improve the number and the quality of solutions.
Of course I like competion too, and leaderboard is like an incentive.
If some players have a little avantage with 3 other top players because they have a better computer, I dont think it is a real problem.
We can have a good rank with less than 10 solutions, and it is very nice.
It is good if a player make a lot of solutions, I am happy for LociOiling, and I hope it helped scientists.
If we want to make sure we dont make always a similar solution, maybe points in this kind of competition should be
in realy validated solutions by scientists.
If 2 solutions are very similars maybe scientist will select only one.
So maybe it will encourage players to play more for science and try more diversity.

The experience was good for me, I tried new solutions each days.
I begined 15, and 8 reached the 10000 points. It is interesting, because now we ask differents questions like :
"How can I improve creating a protein easier ?" "Maybe I need new tools to be more efficiants ?"
So I try to new approachs.

[agcohn821]

Hey folks–thank you all so much for the feedback here, these are all so helpful for us on the team! Questions have also been passed along–super appreciated!

[LociOiling]

Bruno is right about the "industrial" part of this competition.

I started with the primary and secondary structure of my solution to puzzle 1962. This solution was a standard three-helix bundle.

I used AA Edit and SS Edit to apply my 1962 results to a fresh start.

Using idealize secondary structure and cutpoints, I dragged the three helices into rough alignment. I also had the solution from 1962 open in another client as guide.

After stabilizing with shake, wiggle sidechains, wiggle all, Fuzes, etc. I moved the helical bundle close to the target. I used the glycan (the giant sidechain at segment 13) on the target as a rough guide. In some cases, I closed the cutpoints early on, in others I left them open until later.

After getting everything somewhat aligned and somewhat stable, I tried various steps, all on low wiggle power at the start. In some cases, I did something like Mutate No Wiggle or Mutate Combo early. In other cases, I did only a little Mutate All or even went directly to a version of DRemixW.

Some of the solutions went to 10,000 while still on low, others ended with only 9,400 or so.

In most cases, a GAB recipe on medium wiggle power was the next step, followed by a Microidealize or a Cut and Wiggle. Then I moved to something like Worm LWS or Banded Worm Pairs Infinite Filter as a finishing recipe.

I haven't looked at all my solutions in detail, but I did keep a spreadsheet with the primary structure of each one. From the spreadsheet, I can see that the second half of my solutions all had "kewl" in the same spot, so not as much variation as in the first half.

The industrial process really applied to the second half, when I used less variation in the steps and spent less time on each step. So there was less chance for diversity.

I ended up submitting 48 solutions, so it looks like 5 were rejected as duplicates, or due to user error on my part.

I liked having two weeks to work on solutions, even if the more creative part happened in the first 10 days. This puzzle let me practice my handfolding and rethink the sequence of recipes that I use on many puzzles.

There were some challenges in managing so many solutions. I'll put those in a separate post.

[LociOiling]

The Open/Share Solutions dialog makes it difficult to keep track of multiple solutions. It could use additional filters (such as showing only solutions shared with scientists) and sort options (sort by date, or ascending/descending score). Also, a resizable window and maybe a search box would help.

In a couple of cases, I accidentally shared with group instead of with scientists. I found and fixed at least two or three like that, hope I didn't miss anything.

I started adding a segment note on segment 84 to identify each new start. This is probably a good idea on any puzzle where you start more than one solution.

The segment notes showed another problems. In at least a couple of cases, the solution seemed to change in mid-recipe. So I'd start with solution 6, but solution 3 would be back when the recipe finished. I called that "bleed through".

To get around that issue, I started each new solution in its own uniquely-named track. That stopped the bleeding.

The bleed through issue may result when a recipe does something like restoring a quicksave slot that it hadn't previously saved. Or perhaps restoring recent best without first setting recent best. Or perhaps there's a bug, with recent best one of the usual suspects. I've been seeing a similar problem in Banded Worm Pairs Infinite Filter, but I haven't tracked down the source.

I should have taken notes about each solution, such as which recipe was used and how long it took. I used to keep a spreadsheet like that in early days, but stopped in early days.

I also didn't make as many interim saves as usual, which became a problem in some cases. The limit of 10 solutions shared with self and 10 shared with group was one issue, but open/share solutions getting cluttered was the bigger concern.

Next time, I'd make more local saves just in case something bad but fixable happens. I'd also get back to taking progress notes, maybe using Google Sheets or something similar.

[infjamc]

As I had previously mentioned here, I was able to produce a solution that was technically "abusing the score function"… Despite missing the intended binding site, it was able to score 10,321 (for an 85th percentile finish) thanks to the following:

• The design hydrogen-bonds to the beta sheet via another beta sheet in the anti-parallel direction; and
  
  
• The binding interface was stuffed with large side chains, which was enough to max out the DDG and Contact Surface bonuses. (With so many exposed hydrophobics, I would expect the structure to misfold in reality.)
</ol> Given the possibility of this exploit, I wonder if the bonuses from the objectives should be reduced, or perhaps the 10,000 threshold should be raised further? Or would it make sense to magnify the the interaction energy / hiding penalties for this type of puzzle?

[Bruno Kestemont]

Indeed in banded worm pairs infinite filters, there is a "quickload" bug I didn't find time to fix yet. More than a year that it is on my To Do list ;)

[Bruno Kestemont]

The current competition was quite limited to soloïsts.

Due to the "industrial" character and the many inventive industrial processes I read here, I'm thinking on the same competition, but for groups.

-industrial soloïsts design a lot of first diverse hand folds, and share them to group

-industrial evolvers use computer power to evolve them, one by one, to 10k+ and share them to Scientists

-group as well as all individual players involved are rewarded for end game number of scientifically valid shares

(I know Foldit is able to recognise all contributing players in a puzzle, I don't know if this can be automatized "on the fly" for scoring).

[Bruno Kestemont]

Amazing.

And congrat for your big number of winning shares, and rank 2