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1939: Designable Linker: Coronavirus Spike Binder
Status: Closed

Summary

Name: 1939: Designable Linker: Coronavirus Spike Binder
Status: Closed
Created: 01/06/2021
Points: 100
Expired: 01/13/2021 - 23:00
Difficulty: Intermediate
Description: This is the tenth puzzle in the designable linker series! We are providing parts of two of the best-known designed binders to the SARS-CoV-2 spike, and are challenging players to link them together with a rigid linker! The two helical bundles are the parts of the two binders. They are currently connected with a flexible alanine linker that needs to be redesigned.

We have also included the parts of the actual spike that are within 15 angstroms of the termini of the binders, so you know what regions your binder has to avoid to prevent clashing. The big thing for puzzles like these is to have buried hydrophobics at the interface between the linker and the binder helices to encourage structural rigidity. Packing the linker against the helices can help it maintain its shape. We are allowing for select residues on the binders to be fully designable to encourage hydrophobic packing.

Currently everything is frozen except for the linker and the sidechains of several residues that can pack nicely with any designed linker. The linker residues are completely designable. The two binder domains are held in place with strong constraints.

We have included a few objectives to help players generate well-folded designs. The major new one is the ContactMolecularSurfaceScore objective that was just released into Foldit. This is a combination of two different Rosetta metrics that are supposed to reward complexes where the linker has good shape complementary and low binding energy with respect to the binders. This should help keep the linker rigid. As we get more data on the proper threshold values, we hope that this will help binder design across a range of interfaces. It is a difficult problem to design a linker that can hold the binders in place. This type of puzzle is new for Foldit, and we are excited to see what players come up with! Good Luck!
Categories: Design, Overall

Top Groups

RankGroupScorePoints
1Gargleblasters20,446100
2Go Science20,44471
3Anthropic Dreams20,23449
4Contenders18,97633
5Beta Folders17,65922

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Comments

neilpg628's picture
User offline. Last seen 2 days 1 hour ago. Offline
Joined: 08/01/2019
Groups: Foldit Staff
Objectives

Residue Count (max +250)
Penalizes extra residues inserted beyond the starting 240, at a cost of 25 points per residue beyond 250. Players may use up to 260 residues in total.

Core Existence: LCB1 (max +2400)
Ensures that at least 34 percent of residues are buried in the core of the LCB1-linker unit.

Core Existence: LCB3 (max +2400)
Ensures that at least 34 percent of residues are buried in the core of the LCB3-linker unit.

Core Existence: Linker (max +2400)
Ensures that at least 35 percent of residues are buried in the core of the LCB3-linker unit.

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

SS Design (max +500)
Prohibits CYS residues. Penalizes GLY, ALA residues in sheets. Penalizes GLY, ALA, SER, THR 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)
Checks that the residues near the LCB1 terminus are in helices.

ContactMolecularSurface (max +500)
Checks that the designed linker has an energetically favorable interface with the binders.

Joined: 03/28/2020
Groups: Go Science
CMS not capped?

Seems like the ContactMolecularSurface bonus is not capped to 500pts. I get a bonus in excess of 3000 which is nice for the score but is this intended?

neilpg628's picture
User offline. Last seen 2 days 1 hour ago. Offline
Joined: 08/01/2019
Groups: Foldit Staff
CMS

Unfortunately there were some issues with the CMS objective that will be fixed for future. Any adversarial examples can still be used to test out future objective settings.

Joined: 01/25/2012
Groups: Go Science
The CMS produce wrong Sidechains!
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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, RosettaCommons