puzzle picture
2041: Symmetric Tetramer Design with AlphaFold Predictions
Status: Closed

Summary

Name: 2041: Symmetric Tetramer Design with AlphaFold Predictions
Status: Closed
Created: 09/08/2021
Points: 100
Expired: 09/15/2021 - 23:00
Difficulty: Intermediate
Description: Design a symmetric protein tetramer, with 4 identical chains of 80 residues each! This puzzle enables AlphaFold predictions for the monomer subunit of your design, so you can upload your solution for AlphaFold using the AlphaFold prediction tool. AlphaFold will predict the structure of your monomer subunit only (i.e. in the unbound state, in the absence of other symmetric copies). If you load this prediction, then Foldit will attempt to align the prediction with your solution. If you continue working off of the AlphaFold prediction, you may need to make adjustments at the interface where the monomer subunit interacts with symmetric copies.

This puzzle includes a Secondary Structure Objective, so no more than 50% of your design can form helices. The H-bond Network Objective encourages players to build buried, satisfied H-bond networks at the interface between symmetric chains. H-bond networks are a great way to introduce polar residues at the interface, but it's important that all of the bondable atoms make hydrogen bonds! We've also adjusted the H-bond Network Objective so that poor-scoring H-bonds may not contribute to networks; poor-scoring H-bonds will be displayed in red. This puzzle uses the Buried Unsats Objective, with a large penalty for buried polar atoms that can't make H-bonds. In this puzzle, there are no limits on the Complex Core, but we've included the Complex Core objective so players can see the core residues that can be incorporated into H-bond Networks.
Categories: Design, Overall, Symmetry

Top Groups

RankGroupScorePoints
1Gargleblasters22,637100
2Beta Folders22,33670
3Go Science22,33547
4Anthropic Dreams22,04030
5Marvin's bunch21,21819

Top Evolvers

Top Soloists



Need this puzzle? Log in to download.  

Comments

bkoep's picture
User is online Online
Joined: 11/15/2012
Groups: Foldit Staff
Objectives

Buried Unsats (max +500)
Penalizes polar atoms that cannot make hydrogen bonds, -200 points per atom (not including symmetric copies).

Core Existence: Monomer (max +2200)
Ensures that at least 22 residues are buried in the core of the monomer unit.

Core: Complex (max +0)
Awards no bonuses or penalties. Click Show to see which residues count as "Core" for the H-bond Network objective.

H-bond Network (max +2400)
Rewards networks that comprise at least 2 H-bonds involving core residues.
Between 1 and 12 H-bonds should cross the interface between symmetric units.
Networks must be at least 75% satisfied (i.e. 75% of all bondable atoms in a network must make a H-bond).

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

SS Design (max +500)
Penalizes all CYS residues. Penalizes GLY, ALA residues in sheets. Penalizes GLY, ALA in helices.

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.

Secondary Structure (max +500)
No more than 50% of residues may form helices. Extra helices are penalized at 10 points per residue.

Joined: 12/06/2008
Groups: Contenders
Are we ever going to get rid of the penalty for ALA in helices?

Alanine is one of the most common AA's in a real-life helix, yet we are still penalized for incorporating it into our designs.

Many times an alanine in a helix would have fit better into a protein I'm designing than what I am allowed.

I am aware that many of the scripts we use here favor alanine-heavy structures, so that would somewhat limit the diversity the scientists crave. But instead of banning the sidechain, why not set a limit (5%?, 10%) on the number of alanines in helices before a penalty kicks in?

bkoep's picture
User is online Online
Joined: 11/15/2012
Groups: Foldit Staff
Yes

Yes, that is exactly what we would like to do (i.e. set a limit for the entire solution)! This got bumped down the to-do list by the latest AlphaFold features, but we still hope to implement it soon.

To implement it is slightly more complicated than you would think, because the Mutate algorithm assumes that all residue scores are pairwise-decomposable, and a "global" limit violates this assumption. However, we have a way around this now and hopefully we will soon be able to ditch the SS Design Objective.

User login
Download links:
  Windows    OSX    Linux  
Windows
(7/8/10)
OSX
(10.12 or later)
Linux
(64-bit)

Are you new to Foldit? Click here.

Are you a student? Click here.

Are you an educator? Click here.
Social Media


Search
Only search fold.it
Other Games: Mozak
Recommend Foldit
Topics
Top New Users
Sitemap

Developed by: UW Center for Game Science, UW Institute for Protein Design, Northeastern University, Vanderbilt University Meiler Lab, UC Davis
Supported by: DARPA, NSF, NIH, HHMI, Amazon, Microsoft, Adobe, Boehringer Ingelheim, RosettaCommons