1936: Designable Linker: Coronavirus Spike Binder
|Name:||1936: Designable Linker: Coronavirus Spike Binder|
|Expired:||01/06/2021 - 23:00|
|Description:||This is the ninth 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. We have three Core Exists Objectives in the same puzzle. One is for incentivizing hydrophobic interactions between the LCB1 binder and the linker and one is for hydrophobic interactions between LCB3 and the linker. The third is active on the linker alone. The hope is that this way linker designs pack against the binder helices for rigidity while still making sure that the linker is well folded. We have also included a Secondary Structure Objective to incentivize the creation of rigid designs. 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!
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