Placeholder image of a protein
Icon representing a puzzle

1159: gp120 Design: Frozen V3 Hairpin

Closed since over 10 years ago

Intermediate Overall Design

Summary

Created
November 19, 2015
Expires
Max points
100
Description

This puzzle is very similar to Puzzle 1155, except that now the V3 hairpin is frozen in place. We would like players to redesign the residues surrounding the V3 hairpin to try to stabilize this conformation of the HIV-1 Env protein. This puzzle includes an Exploration filter to prevent players from straying far from the starting conformation.



This protein is a portion of the HIV-1 envelope glycoprotein. The HIV-1 Env protein is a trimer of heterodimers--gp120 (the receptor binding domain) and gp41 (the transmembrane and fusion domain)--and is found on the surface of the HIV-1 virus. The HIV-1 Env complex is responsible for recognizing and binding to a human immune cell through its receptors. When gp120 binds to the human receptors (CD4 and CXCR4 or CXCR5), dramatic conformational changes occur in gp120 and gp41 that cause the virus to fuse with and infect the human cell. This structure of gp120, in a pre-fusion conformation, was recently obtained by x-ray crystallography. However, we know that the V3 loop of gp120 (which exists as a beta-hairpin here) can move in solution, allowing binding of antibodies that will clash with this pre-fusion conformation. We would like to stabilize the Env protein in this conformation so we can use it to raise potent antibodies against HIV.

Top groups

  1. Avatar for Anthropic Dreams
    1. Anthropic Dreams
    100 pts. 89,301
  2. Avatar for Void Crushers 2. Void Crushers 78 pts. 89,225
  3. Avatar for Contenders 3. Contenders 60 pts. 89,194
  4. Avatar for Beta Folders 4. Beta Folders 45 pts. 89,182
  5. Avatar for Go Science 5. Go Science 33 pts. 89,134
  6. Avatar for Gargleblasters 6. Gargleblasters 24 pts. 89,086
  7. Avatar for L'Alliance Francophone 7. L'Alliance Francophone 17 pts. 88,964
  8. Avatar for Deleted group 8. Deleted group pts. 88,927
  9. Avatar for HMT heritage 9. HMT heritage 8 pts. 88,911
  10. Avatar for Italiani Al Lavoro 10. Italiani Al Lavoro 6 pts. 88,607
  1. Avatar for Bruno Kestemont 11. Bruno Kestemont Lv 1 82 pts. 89,056
  2. Avatar for gmn 12. gmn Lv 1 80 pts. 89,055
  3. Avatar for Vredeman 13. Vredeman Lv 1 79 pts. 89,054
  4. Avatar for egran48 14. egran48 Lv 1 77 pts. 89,032
  5. Avatar for Norrjane 15. Norrjane Lv 1 75 pts. 89,009
  6. Avatar for bertro 16. bertro Lv 1 74 pts. 89,001
  7. Avatar for Mark- 17. Mark- Lv 1 72 pts. 88,991
  8. Avatar for gloverd 18. gloverd Lv 1 71 pts. 88,981
  9. Avatar for lynnai 19. lynnai Lv 1 69 pts. 88,979
  10. Avatar for actiasluna 20. actiasluna Lv 1 68 pts. 88,972

Comments

LociOiling Lv 1

The huge negative ideality found in 1155 is gone, but scores in this puzzle seem to be running 10 times greater than I'd expect based on the total of the segment scores.

Is this high scoring intended?