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1912b: Designable Linker: Coronavirus Spike Binder

Closed since almost 2 years ago

Intermediate Overall Design


November 05, 2020
Max points

Note: This puzzle replaces Puzzle 1912 which was posted with an erroneous BUNS Objective. Players may not load solutions from the original Puzzle 1912.

This is the first 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 20 angstroms of the termini of the binders, so you know what regions your binder has to avoid to prevent clashing.

Currently everything is frozen except for the linker and a portion of the helix on each binder. These residues are designable, but only residues on the linker itself can be added and deleted. The two binder domains are held in place with strong constraints.

We have included a few objectives to help players generate well-folded designs. This puzzle uses the Buried Unsats Filter only on the linker to make sure buried polar atoms are making hydrogen bonds. 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!

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bkoep Staff Lv 1

Residue Count (max +550)
Penalizes extra residues inserted beyond the starting 205, at a cost of 55 points per residue. Players may use up to 215 residues in total.

Core Existence (max +2400)
Ensures that at least 28 percent of residues are buried in the core of the monomer unit.

Buried Unsats (max +500)
Penalizes polar atoms that cannot make hydrogen bonds, -60 points per atom.

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, SER, THR in helices.

HuubR Lv 1

This is an exciting new type of puzzle, and I was very motivated to give it my best shot, but then I ran into something I do not understand.

The puzzle description above says that we have "two of the best-known designed binders", and I can understand that these are fixed in space with strong constraints (the thin red lines, when you move a part out of position). And the description of the first image in Coronavirus Designable Linker Puzzles says "The binders have been […] augmented with helices to bring their termini closer together". As I see it, those are the parts of the helices that are all Valine (residues 76-92 and 131-142). These are supposed to be designable. Why, then, are these also constrained in space? If I want to redesign part of these helices, I can mutate, but I cannot bend the backbone, not even a little bit, without a huge penalty in points. Let alone replacing part of these helices with another structure.

In my mind, this will not help to get diverse and creative solutions!

It could well be that I'm just missing something here, so if anyone can explain this to me, that would be greatly appreciated.


I cannot best advise to the above questions.

Furthermore is there anyone who knows how to resolve a problem with an information pin placed at segment 132 (at beginning of puzzle this is Glutamate)and segmented one this makes also segment 131 to score poor (no good state) . The information pin says that we can use the idealize tool but if you try to use it a lot of bad thing's happen and all the structure become a mesh with constrained red lines!!

I experience also that in some puzzles and probable this one a)design freedom is relative, well notice that we do not have the SARS CoV-2 surounding structure b)processing power is important to some puzzles to achieve higher energy scores because it clearly relates to effective combinations except if you have a very good idea about the solution c) the efficiency of recipes (lua algorithm) is important. In conclusion is not only human creativity (only playing) but all above mentioned which contribute to the final result as well knowing the very details of using this software (playing skills).

neilpg628 Staff Lv 1

Yes, for that puzzle the helices were mutable but not deletable or designable. That is now changed for the newer Designable Linker Puzzle being released today.