puzzle picture
1507b: Malaria Vaccine Design
Status: Closed

Summary

Name: 1507b: Malaria Vaccine Design
Status: Closed
Created: 04/11/2018
Points: 100
Expired: 04/17/2018 - 23:00
Difficulty: Intermediate
Description: Note: This puzzle replaces Puzzle 1507, which was posted with an erroneous puzzle setup. Unfortunately, players will not be able to load solutions from the original Puzzle 1507.

Design a protein that could be used as a vaccine for malaria! Malaria is a deadly disease caused by the parasite P. falciparum, which makes circumsporozoite protein (CSP) to grow and infect human cells. The human immune system can combat malaria by producing antibodies that recognize CSP on the surface of the parasite. However, the immune system is not always successful, in part because CSP is a highly flexible protein that can exchange between different structures. It was recently discovered that human antibodies can protect against malarial infection if they bind to a CSP loop in a particular "vulnerable" structure; but antibodies targeting alternative structures of CSP do not halt infection. If we can design a protein that contains the CSP loop in the vulnerable conformation, the protein could be used as a vaccine to prepare the immune system against malaria (by raising antibodies that bind the vulnerable CSP structure)!

In this puzzle, Foldit players can design a protein that contains the CSP loop. The backbone of the CSP loop is frozen, but players can fold and design residues on either side of the loop. Also included, for context, is a frozen portion of an antibody that binds the CSP loop. Players begin with 60 designable residues, and can add up to 10 additional residues at a cost of 32 points per residue.
Categories: Design, Overall

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Comments

SaraL's picture
User offline. Last seen 17 hours 37 sec ago. Offline
Joined: 09/20/2011
Groups: Gargleblasters
Broken protein?

The locked portion of the protein seems erroneously arranged: there are sheets that seem odd in appearance and sections of loops with 90 degree angles and completely straight sections crossing from one side of the protein and connecting to the other while overlapping other loops.

SaraL's picture
User offline. Last seen 17 hours 37 sec ago. Offline
Joined: 09/20/2011
Groups: Gargleblasters
more stuff

Additionally attempting to rotate a sheet segment will rotate the entire loop as if it is a solid part of the sheet, disconnecting the cut end from the locked portion.

bkoep's picture
User offline. Last seen 11 hours 12 min ago. Offline
Joined: 11/15/2012
Groups: None
Trimmed protein

The antibody protein (the locked region that cradles the CSP loop) has been trimmed in this puzzle, which causes this region to look funny.

The full antibody protein is much larger, but in this puzzle we only need to model the portion close to the CSP loop. By trimmed a few hundred residues from the antibody protein, this puzzle should be run a little easier and be more responsive. Rest assured, those weird segments that seem to crisscross the frozen region are just visual artifacts. This does not represent the actual protein structure and should not affect scoring.

Your second comment is a little concerning. Do you mean that the locked CSP loop moves? Can you share your solution using the Share with Scientists feature?

Joined: 10/30/2012
Groups: Beta Folders
crashing when running mutate

crashing when running mutate scripts

bkoep's picture
User offline. Last seen 11 hours 12 min ago. Offline
Joined: 11/15/2012
Groups: None
Hmm

That's not good. Any chance you could post the log.txt file from a crashed client?

Is the crash easily reproducible? Can you describe exact steps to reproduce so we can try to track down the bug on our end?

Joined: 06/24/2008
Groups: Void Crushers
Selecting

1507b is acting funky; sometimes it is hard to select

It seems to be a problem when you have the recipe output window open

Joined: 06/24/2008
Groups: Void Crushers
Show Output

Definitely the Show Output box is acting funky.

Joined: 06/24/2008
Groups: Void Crushers
BTW

I am on MAC and using devprev

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Developed by: UW Center for Game Science, UW Institute for Protein Design, Northeastern University, Vanderbilt University Meiler Lab, UC Davis
Supported by: DARPA, NSF, NIH, HHMI, Microsoft, Adobe, RosettaCommons