Design a binder against coronavirus! This is a followup to Puzzle 1805b, which challenged players to design an antiviral protein that could bind to the 2019 coronavirus and disrupt viral infection. This puzzle has some small improvements, and allows players to continue working on antiviral designs. See the Foldit blog for a quick look results from Puzzle 1805b, with some tips for making a successful protein binder! Players may load in solutions that were saved in the previous puzzle.
In late 2019, a new highly-infections virus emerged out of Wuhan, China. This virus belongs to the coronavirus family, and is similar to the virus that caused the SARS epidemic in 2002. Coronaviruses display a "spike" protein on their surface, which binds tightly to a receptor protein found on the surface of human cells. Once the coronavirus spike binds to the human receptor, the virus can infect the human cell and replicate. In recent weeks, researchers have determined the structure of the 2019 coronavirus spike protein and how it binds to human receptors. If we can design a protein that binds to this coronavirus spike protein, it could be used to block the interaction with human cells and halt infection!
In this puzzle, players are presented with the binding site of the coronavirus spike protein. The backbone and most of the sidechains are completely frozen, except for flexible sidechains at the binding site, where the spike protein normally interacts with the human receptor protein. Players can design a new protein that binds to these sidechains, blocking interactions with the human receptor. In order to bind the coronavirus target, designs will need to make lots of hydrophobic contacts and H-bonds with the flexible sidechains at the binding site. But designs will also need to have lots of secondary structure (helices or sheets) and a large core, so that they fold up correctly! See the puzzle comments for Objective details.
Objectives
Residue Count (max +550)
Penalizes extra residues inserted beyond the starting 192, at a cost of 55 points per residue. Players may use up to 202 residues in total.
Core Existence (max +2400)
Ensures that at least 28 percent of residues are buried in the core of the monomer unit.
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.
SS Design (max +500)
Penalizes all CYS residues. Penalizes GLY, ALA residues in sheets. Penalizes GLY, ALA in helices.
This puzzle lets you continue work on your 1805b results, but evolver mode is a problem, since solutions load with much lower score, but evolving them still requires adding two points to the 1850b score.
For example, my 1805b solution scoring 16,534 loaded at 15,704 in 1808. But it still wants 16,536 to evo. I saw similar results in other solutions. I'm guessing that most of the evolvers are working on new solutions.
This Coronavirus is a killer. I send my prayers to the families of the dead to this horrible disease. If one of us could crack this case, lives would be saved. As a society we must solve this. Please help everyone this needs to be solved. Nobody else should die.
