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1650: B7-2 Binder Design: Stabilize the Loop!

Closed since over 3 years ago

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Summary


Created
March 18, 2019
Expires
Max points
100
Description

Note: This puzzle was closed early due to a miscalibrated score function. The puzzle has been reposted as Puzzle 1650b.



Design a protein to bind B7-2 and block autoimmune reactions! B7-2 is a signal protein in the immune system, and is important for regulating how the immune system distinguishes foreign particles from “self" cells. In some autoimmune disorders, like rheumatoid arthritis, B7-2 can activate the immune system against the body’s own self cells. We want to design a protein that binds B7-2 and blocks it from activating the immune system. Here we’ve provided the target surface of B7-2, along with a a few loop residues from a known binder of B7-2. We want to see if Foldit players can design a folded protein that contains this loop! The B7-2 surface and the binding loop are frozen in place. Good designs should form a well-folded protein that stabilizes the proline-rich binding loop. The starting structure contains 122 residues, but players may add residues at a cost of 55 points each (maximum 130 residues).

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Comments


NinjaGreg Lv 1

I can see a few issues with the design of this puzzle. First, it would appear that segments 69 and 70 are locked, so if 70 is part of a helix one can't use the "5" key to get an ideal helix. Second. the band between the two sheet segments (91-92, 99-100) can't be clicked on to create a solidified sheet. Third, the score seems to be hugely negative at all times. Fourth, having the fixed portion in the middle of two loops really constrains what can be done. Just sayin'.

bkoep Staff Lv 1

This puzzle has been closed and reposted as Puzzle 1650b.

I'm sorry to say we can't address all of these issues. The cutpoints are permanent, and cannot be closed. This is important for keeping the loop frozen in place.

The constraint of having the fixed portion in the middle of the chain is what makes this puzzle especially challenging! Currently, we don't have great automated methods for "growing" a protein design out of a fixed loop like this. We think Foldit players might be better-suited to tackle this kind of problem.