Design a binder against coronavirus! This puzzle introduces new binder metrics to measure the DDG, SASA, and Shape Complementarity of your design. Because the metrics are slow and must be run manually, they are available as optional Objectives and will not award any bonuses or penalties. To calculate these metrics, open the Objectives dropdown panel and click "Run All." Other Objectives are still in effect. This puzzle prohibits SER and THR in helices, which may make it harder to satisfy BUNS, but should help the helices to fold correctly. Remember, if your designed protein creates Buried Unsats, then it will be less likely to fold and bind to the coronavirus target. (Note that this target protein includes 8 buried unsats that players may be unable to fix.) See the blog for more details about buried unsats, and for helpful tips to make a successful protein binder! Players may not load solutions from previous puzzles.
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.
Because if your protein is actively changing, even fractional points, running ANY of the New Metric filters is going to produce a different result.
For me, with no tool running, they all consistently reports the same score (even if ran individually).
To answer that for him, no he was not Wiggling. All he's doing is, with a "still" protein, pressing Run on DDG.
Since OWM and I are on the same team, I'm able to load his share.
I can confirm that for his pose, it does in fact churn out different results for DDG on almost ever Run.
My Tests: -18.8, -20.4, -18.8, -18.8, -19.2, a few minutes later pressed again -19.2, -18.9
SASA and SC do not vary. This also occurs when using Run All.
While I can't say I've personally ever ran the filters multiple times back to back on the same pose, I did try on my own design before loading OWM's, and mine did not exhibit this, only his Shared pose does.
Officially adding it to the internal Google Doc (my Community Crash Compendium) since it's reproducible on two systems, across different OS environments.
Good catch! There is a random component to the algorithm in the DDG Objective. In the future, we can simply turn off this random component, but in the long term we should probably try to come up a better non-random alternative for this component.
