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?
1159: gp120 Design: Frozen V3 Hairpin
Closed since over 10 years ago
Intermediate Intermediate Overall Overall Design DesignSummary
- Created
- November 19, 2015
- Expires
- Max points
- 100
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.
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