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1924: Designable Linker: Coronavirus Spike Binder
Status: Closed


Name: 1924: Designable Linker: Coronavirus Spike Binder
Status: Closed
Created: 12/02/2020
Points: 100
Expired: 12/09/2020 - 23:00
Difficulty: Intermediate
Description: This is the fifth 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. Note that this puzzle has as different starting structure than previous puzzles and is about linking a different pair of the same binders.

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. They are the same as in the previous puzzle. 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

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neilpg628's picture
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Joined: 08/01/2019
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Residue Count (max +550)
Penalizes extra residues inserted beyond the starting 240, at a cost of 55 points per residue. Players may use up to 250 residues in total.

Core Existence (max +2400)
Ensures that at least 35 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.

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.

Joined: 12/06/2008
Groups: Contenders
Why does puzzle 1924 score so much lower...

Why does puzzle 1924 score so much lower than prior designable link puzzles? There is no change in the objective bonuses, and there seems to be little change in the designable section.

neilpg628's picture
User offline. Last seen 34 weeks 1 day ago. Offline
Joined: 08/01/2019
Groups: Foldit Staff
Score Ranges

This is actually a completely different setup from previous puzzles since we are asking you to design a linker between a different set of LCB1-LCB3 termini. It's possible that it is harder to increase your score dramatically in this different configuration. However if you are just talking about the absolute sizes of the score, those are not comparable between puzzles.

APPAAP's picture
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Joined: 04/25/2020
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I also have the same queries about score. I see some players achieving more than 7000 points. This means that they use better algorithms and may much more processing power than mine. Also I want to ask do you manage Ideal Loops earlier or later in the design because I got some problems with it for this particular puzzle. For example if you know what a-helices and sheet to use prior is easy to fix the ideal loops but if you do not know this makes it harder.

Joined: 03/28/2020
Groups: Go Science
Score and ideal loops

You can achieve these high scores with a clean and stable hand-folded design and the proper optimization-recipes. I use mostly: Cut and wiggle, bandfuze, banded worm pairs, jet or sd multiwalk forever, acid tweaker/tweeker and random idealize. These generally squeeze out enough points provided your design is stable. With stable I mean that it does not form unideal loops when wiggling globally. I try to clean up unideal loops as early as possible. Remix can be used for this or sometimes I have to handfold loops and surrounding segments anew or cut them up and redo. If there is too much torsion or stress in general present on parts of your design it will increase the likelihood that unideal loops will form. So you should take care early that nothing looks too twisted or odd. In terms of the interconnecting cut in the linker between the two binders, I try to put this in a Helix and then use the scheme with bands from n to n+3 and n to n+4 over the cut as it was shown in one of the last newsletters. Then wiggle and the helix will connect nicely with some practice. This only works of course if the helix is correctly pre-aligned and phased (meaning it should look roughly around the cut as if you would cut up an ideal helix). For initial alignment I use Rama map, dragging or bands. Take care that in this step nothing is already overly stressed or skewed. Otherwise adapt your design.
This is my personal opinion which works well for me. Others may have different views, strategies or recommendations. Just experiment with it and find out what fits for you. Happy folding, iwdn

agcohn821's picture
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Joined: 11/05/2019
Groups: Foldit Staff

Hi there--thank you for these suggestions! I have also passed the questions from others along to the team.

APPAAP's picture
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Joined: 04/25/2020
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Score and ideal loops above

Thank you for you kind answer. It makes some mentioned subjects more clear to me.

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