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2115: CD22 Binder Design: Round 2
Status: Closed

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bkoep's picture
User offline. Last seen 2 hours 12 min ago. Offline
Joined: 11/15/2012
Groups: Foldit Staff
Objectives

DDG Metric (max +2000)
The predicted binding energy of your design. The goal DDG is -40.0 or less.

Contact Surface (max +2000)
Measures how much of your binder surface is in close contact with the target protein. The goal Contact Surface is 500 or more.

Buried Unsats (max +500)
Penalizes 10 points for each polar atom that cannot make any hydrogen bonds.

Core Existence (max +1500)
Ensures that at least 25 percent of residues are buried in the core of the monomer unit.

Interaction Energy (max +500)
Monitors that all large PHE, TYR, and TRP residues are scoring well.

Ideal Loops (max +500)
Penalizes any loop region that does not match one of the Building Blocks in the Blueprint tool. Use "Auto Structures" to see which regions of your protein count as loops.

SS Design (max +500)
Disabled use of CYS residues.

Neural Net (max +0)
Achieve an AlphaFold prediction confidence of 80% or more.

Joined: 12/06/2008
Groups: Contenders
BUNS objective too lenient?

You decreased the BUNS penalty by ninety-five percent, effectively making it meaningless in a puzzle where a typical score is well over ten thousand.

Is this what you really wanted? A penalty of fifty or a hundred, instead of ten, would have done the job.

Why, after years of seeing a BUNS penalty in every design puzzle, are BUNS now being almost completely ignored?

bkoep's picture
User offline. Last seen 2 hours 12 min ago. Offline
Joined: 11/15/2012
Groups: Foldit Staff
Probably too lenient

The BUNS penalty decrease is inspired by some fruitful discussion on the Foldit blog, in response to our post about IL-2R binder experiments.

It was suggested that the BUNS Objective might impede other design Objectives (like Contact Surface) if our BUNS requirements are too stringent. We think this idea has some merit, so we want to see if a smaller BUNS penalty has an effect on other Objectives in top-scoring designs.

Many of our binder design objectives (including BUNS) came out in a flurry during our SARS-CoV-2 spike binder campaign, so we don't have such a clear picture about how each of these Objectives affects Foldit gameplay and aggregate results. Because the BUNS Objective is less robust than other Objectives, we would like to be sure that BUNS penalties do not have an overpowering effect on other design metrics.

BUNS are still important, and players should continue to beware of these atoms! But, if you think you can sacrifice one BUNS atom to get 10 points elsewhere, then we want to see how you can do it!

In the next couple of weeks, we will likely continue this experiment with other binder design targets. I think you are probably right that a 90% penalty reduction is overkill. However, if the BUNS penalty is in fact detrimental to other design metrics, then we are certain to see some effect from such a drastic penalty decrease.

alcor29's picture
User offline. Last seen 6 hours 44 min ago. Offline
Joined: 11/16/2012
fold it crashing

Can't load anything. See addition by gmn on feedback and notes on discord vet channel.

nspc's picture
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Joined: 03/26/2020
Groups: Go Science
buns

I tested some recipes with new BUNS score, it increases other objectives, like CS and DDG (-50 ddg and 500 cs). But there is often lot of BUNS left. Some can be removed with hand foldiding, so we can go from 8 BUNS to 5 sometimes. Is is interesting to share solution with hight CS and DDG but with like 4 or 5 buns ? If yes I will share them more.

bkoep's picture
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Joined: 11/15/2012
Groups: Foldit Staff
Yes!

Yes, please share! We would like to see what kinds of BUNS atoms result from this adjust penalty.

nspc's picture
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Joined: 03/26/2020
Groups: Go Science
Alanine

There is Alanine allowed on helix. I dont know if it is intentional

bkoep's picture
User offline. Last seen 2 hours 12 min ago. Offline
Joined: 11/15/2012
Groups: Foldit Staff
Yes

We are trying to allow ALA on more design puzzles. We hope the AlphaFold tool will discourage some of the problems associated with excessive ALA.

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Developed by: UW Center for Game Science, UW Institute for Protein Design, Northeastern University, Vanderbilt University Meiler Lab, UC Davis
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