1920: MERS-CoV Binder Design: Round 5
||1920: MERS-CoV Binder Design: Round 5
||11/27/2020 - 23:00
||Note: Due to strange behavior and frequent hangs, this puzzle has been reduced to zero points. Players should not feel compelled to play it for competitive reasons. However, the results of this puzzle have exceptional scientific value, so the puzzle will remain active for those who wish to keep working. Once we find and fix the bugs, we intend to repost the puzzle so that players may load previous work and continue competitive play.
Design a binder for the viral spike of MERS-CoV! The latest update lets us use DDG and Contact Surface as regular Objectives, instead of as background Metrics. Contact Surface captures some of the same info as both SASA and SC, and is even better at selecting successful binder designs in the lab. Contact Surface favors binders with large interfaces that closely follow the contours of the target. DDG and Contact Surface have a ramped bonus; as you improve DDG and Contact Surface, you will get an increasing bonus until you reach the threshold of DDG < -40 or Contact Surface > 400, and then the bonus will be capped.
MERS is a respiratory disease similar to COVID-19, and is caused by a related coronavirus. There have been several MERS outbreaks since 2012, but there is still no treatment has been developed for the disease. The MERS-CoV virus is coated with a spike protein that recognizes the human protein DPP4, which is found on the surface of lung cells. A protein that binds to the MERS-CoV spike could be used as a drug to block DPP4 recognition and slow viral infection.
In this puzzle, players are presented with the binding site of the MERS-CoV 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 MERS-CoV target, designs will need to make lots of hydrophobic contacts and satisfy any polar atoms that are buried at the interface. 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.
Need this puzzle? Log in to download.