Protein Design Partition Tournament
We are announcing a friendly protein design tournament for Foldit players! This tournament is something of an experiment, and we are not sure exactly how it will unfold. Participation in the tournament is completely voluntary, and we will continue to post regular Foldit puzzles during the tournament, for those who do not wish to participate. There will be no prizes (except for bragging rights and a rare new Foldit Achievement), and we cannot guarantee that any scientific results will arise from the tournament. The main purpose of the tournament is to have fun folding proteins, and to inspire Foldit players to think differently about protein design; but we do also think the tournament could lead to higher quality protein designs.
Unlike our regular design puzzles, in which players compete to design proteins with the best absolute energy, this tournament is designed to reward proteins with the best energy landscape. For more discussion about energy landscapes, see parts one and two of this blog series.
The tournament will take place in two phases, over the next 6 weeks.
Phase One: Defense
The first phase of the tournament will take the form of a Foldit design puzzle, similar to the regular Monomer Design puzzles that are posted every week. Players will have two weeks to craft their best protein design, which will have to defend itself in Phase Two. To enter the tournament, players must share their chosen design with scientists, using the Upload for Scientists button in the Save Solution menu. When you save your solution, give it the title ‘Tournament Submission’ in the Save Solution dialog box. Every player is allowed one tournament submission. If a player submits multiple solutions, only the most recent solution will be accepted. For the sake of competition logistics, team play will not be allowed in the tournament; only soloist solutions will be accepted.
The Phase One design puzzle will include two objectives:
Residue Count: Designs may contain 70-100 residues, at a cost of 32 points per residue.
Secondary Structure: Designs may be up to 10% α-helix.* Additional helices will be penalized at 10 points per residue.
*We will accept Phase One submissions regardless of their secondary structure content. However, we’d like to discourage players from submitting helical bundles and ferredoxin-like folds (a.k.a. "surfing hotdogs") that typically score well in regular design puzzles. Rather, this is a chance for players to showcase designs that aren’t normally competitive in regular design puzzles.
Phase Two: Offense
Twenty Foldit player submissions will be selected to advance to Phase Two:
Five will be the five top-scoring submissions from Phase One.
Five will be hand-selected by the Foldit team, on merits of creativity and plausibility.
Ten will be chosen at random from the remaining submissions.
For each of the 20 selections, we will create a special Partition Contest using the selected protein design. Each contest will be set up as prediction puzzle, similar to the regular De-novo Freestyle puzzles, except that the starting structure will be the fully-folded design. All 20 Partition Contests will be open to the entire Foldit community and will remain online for four weeks, during which time the selected designs will be vulnerable to “challenge.” Any Foldit player can challenge a design by joining its Partition Contest and attempting to refold the design into another high-scoring decoy structure.
The Phase Two contests will include an RMSD Objective: All solutions must differ from the starting model with an RMSD of at least 2.5 Å.
Ultimately, each design in the tournament will be evaluated by its partition function (described in the previous blog post), based on the decoys found by challengers in the Phase Two contests.
By challenging a design and finding a high-scoring decoy, you show that your opponent's sequence does not have 100% probability of adopting the folded structure, and that its partition function must be shared with your decoy structure. You effectively stake a claim in the partition function of that design; the higher the score of your decoy, the larger your claim in the opponent's partition function.
A player may make multiple challenges against a single design; in some cases, it may be more effective to make many moderate-scoring challenges rather than a single high-scoring challenge. In order to calculate the partition function for a design, we will cluster all of the contest solutions to identify representative states. Then, we’ll use the partition function to determine the probability of each state.
Unfortunately, we cannot calculate the partition function on the fly, so players can only estimate how well a design is resisting challenge by following the Contest leaderboards. However, we will post weekly updates throughout Phase Two, with updated partition functions for all 20 Contests.
The champion of the tournament will be the protein design with the highest probability, as determined by its partition function.
There will also be Achievements for the most effective challengers, who are able to stake the greatest claims in the partition functions of their opponents.
Finally, we’d like to point out that, while players may be tempted to aim for a high-ranking design in Phase One, what really counts is how well each design can withstand challenges in Phase Two. If you design a high-scoring protein in Phase One, but its sequence is also compatible with many high-scoring decoy structures, then in Phase Two challengers will easily find high-scoring decoys and stake large claims in your design’s partition function.
The Phase One design puzzle is online now! Happy folding!( Posted by bkoep 68 519 | Thu, 08/30/2018 - 20:54 | 27 comments )