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425: H2N2 Flu Design Puzzle 1

Closed since almost 15 years ago

Intermediate Overall Design

Summary

Created
May 29, 2011
Expires
Max points
100
Description

This is the first of the many new exciting Flu puzzles David Baker mentioned in his blogpost. Our lab designed against the H1N1 subtype of the virus, but a related subtype with pandemic potential, H2N2, has different sidechains in this region that perturb binding. The goal is to design the interface of these designs so that it can bind to the H2 subtype of Influenza. This puzzle is worth 150 global points! If you are new to Foldit, make sure you have completed the Intro Puzzle 4-5 and Design Puzzles 6-1 through 6-4.

Top groups

  1. Avatar for hhv9 21. hhv9 1 pt. 7,653
  2. Avatar for Penny-Arcade 22. Penny-Arcade 1 pt. 7,651
  3. Avatar for Slovak National Team 23. Slovak National Team 1 pt. 7,638
  4. Avatar for Deleted group 24. Deleted group pts. 7,630
  5. Avatar for Crunching Family 25. Crunching Family 1 pt. 7,630
  6. Avatar for Czech National Team 26. Czech National Team 1 pt. 7,615
  7. Avatar for Piratenpartei Deutschland 27. Piratenpartei Deutschland 1 pt. 7,548
  8. Avatar for Cannabis Crew 28. Cannabis Crew 1 pt. 7,544
  9. Avatar for Rechenkraft.net 29. Rechenkraft.net 1 pt. 7,527
  10. Avatar for Extraterrestrials 30. Extraterrestrials 1 pt. 6,916
  1. Avatar for marie_s
    1. marie_s Lv 1
    100 pts. 7,741
  2. Avatar for BootsMcGraw 2. BootsMcGraw Lv 1 99 pts. 7,741
  3. Avatar for vertex 3. vertex Lv 1 97 pts. 7,740
  4. Avatar for wld333 4. wld333 Lv 1 95 pts. 7,740
  5. Avatar for Grom 5. Grom Lv 1 93 pts. 7,739
  6. Avatar for krulon 6. krulon Lv 1 91 pts. 7,736
  7. Avatar for Mark- 7. Mark- Lv 1 89 pts. 7,736
  8. Avatar for caglar 8. caglar Lv 1 88 pts. 7,732
  9. Avatar for steveB 9. steveB Lv 1 86 pts. 7,732
  10. Avatar for mimi 10. mimi Lv 1 84 pts. 7,732

Comments

beta_helix Staff Lv 1

In order to play this exciting puzzle (worth 150 global points) make sure to download the latest update (it should download automatically when launching Foldit).

saksoft2 Lv 1

When 425 finishes, are you going to re-release the top 8 or so mutation combinations in an alignment puzzle without the locking of the mutated backbone?

I mean it is unrealistic to think that we can mutate long segments of this drug without affecting the shape of the secondary structures we are mutating, right? I believe that unlocking those structures would really help us to help you to design a better bonding drug.

What is the intent of allowing those segments to mutate without allowing them to be flexible?

TheGUmmer Lv 1

Why are the backbone scores for segments 305 and 317 so bad?

I have a backbone score on 305 at the moment as -1999 and 317 as -2000. There is no way to improve this as they are locked.

This can't be the natural state for them, can it?

beta_helix Staff Lv 1

Those crazy scores are due to the constraints on both those key amino acid sidechains.

As you mentioned, all the backbone values are fixed so there is no way to improve them (but as you probably noticed, due to the constraints on them you can make both scores worse by pulling 305 and 317 too far away ).
These bad initial scores are constants and are simply artifacts of the constraints, they do not represent anything wrong with the topology of the drug and score perfectly fine without the constraints.

You'll be able to see this in future versions of this Flu puzzle (to answer saksoft2's question) when we allow you to modify parts of the structure.

saksoft2, we wanted to start with a more conservative initial puzzle rather than let you change everything only to have the top solutions all come back with a giant helix or something ;-)

Ideally, if a Foldit player can come up with a single design that binds H2N2 and it is also able to bind other subtypes that would be perfect, right?

itskimo Lv 1

looks like the groups were spread more evenly across the score board. I hope this is a good thing ? :)