1112: Compact 25-residue Marburg virus inhibitor

Closed since over 10 years ago

Summary

• Created: July 10, 2015
• Expires: July 18, 2015 at 23:00 UTC
• Max points: 100

Description

This is a continuation of our series of Marburg inhibitor peptide puzzles. We'd like you to design a 25-residue peptide that's able to inhibit the Marburg glycoprotein, a viral surface protein that allows the Marburg virus to infect cells. Smaller size can make it easier for a peptide to pass through barriers, such as the gut-blood barrier or the blood-brain barrier, and can also make it less likely to trigger an immune response. It also opens up the possibility of chemically synthesizing the peptide, which can mean both that it's easier to make large amounts and that we can include unnatural amino acids or other chemical modifications that would not be possible in a protein that's expressed in bacteria or yeast, but which might aid function or stability. The flip side, though, is that it's more challenging to design something that folds well and binds with high affinity and specificity in this small size range -- but that's the challenge!



If you haven't done so aleady, take a look at our recent blog posts providing feedback on past Marburg puzzles (here and here). We'd like nice, compact designs that bury a sizable hydrophobic core, have no voids in their cores, have lots of secondary structure (helices and sheets) and have good disulfide bonding patterns. Players should also try to maximize contacts (especially hydrophobic contacts) between the peptide and the target. We suspect that designs with a helix lying across a two-standed sheet will work best in this puzzle, but that's not carved in stone.



Be creative! Good luck!

Top groups

• 11. HMT heritage 7 pts. 8,676
• 12. Russian team 5 pts. 8,551
• 13. CureCoin 4 pts. 8,474
• 14. xkcd 3 pts. 8,125
• 15. foldeRNA 2 pts. 7,367
• 16. Natural Abilities 1 pt. 7,255
• 17. SETI.Germany 1 pt. 7,172
• 18. FoldIt@Netherlands 1 pt. 6,816
• 19. Eὕρηκα! Heureka! 1 pt. 6,584
• 20. Czech National Team 1 pt. 6,240

Top soloists

• 1. Bletchley Park 100 pts. 10,713
• 2. Bruno Kestemont 99 pts. 10,664
• 3. mirp 97 pts. 10,656
• 4. dembones 96 pts. 10,635
• 5. MurloW 94 pts. 10,629
• 6. Galaxie 92 pts. 10,625
• 7. gurra66 91 pts. 10,618
• 8. steveB 89 pts. 10,612
• 9. Museka 88 pts. 10,592
• 10. frood66 86 pts. 10,589

Comments

[Susume]

This puzzle seems considerably slower than 1108 - 1108 was playable; this one is barely so.

[Bruno Kestemont]

Is it normal that a fragment malus remains on the virus protein?

[bkoep]

This was acknowledged in the previous Marburg puzzle, but we neglected to mention it here.

There are segments of the Marburg glycoprotein and the binding hairpin that violate the Fragment Filter. They should be no cause for concern, since they cannot be corrected and will affect all players equally.

[retiredmichael]

maybe we need hydrogen bond networks, finding my various versions spreading apart and moving away from target as my score goes up