Closed since over 6 years ago
Advanced Overall DesignHelp design a protein for cancer treatment!
Integrins are cell adhesion proteins that are normally inactive on the surface of cells. Once activated by a binding partner, integrins can induce changes in cell cycle, growth factor signaling pathways, cytoskeletal organization, and movement. In some types of cancer, integrins are involved in promoting tumor metastasis and cancer blood vessel formation. We'd like to design an integrin antagonist, which can block regular binding partners and keep integrin in the inactive state!
Integrin is a very large protein, and this puzzle includes only the binding portion of integrin. The integrin backbone is completely frozen, but some sidechains on the surface are allowed to move. Foldit players start with 6 loop residues already placed in the binding pocket; these residues are frozen in place and cannot move, but players have complete freedom to fold and design 65 residues flanking the frozen loop.
In this puzzle, we'd like Foldit players to focus on designing a compact protein with a significant core, so we've added a Core Existence objective with a large bonus value. We think successful antagonists will also need to make at least one other major contact with the integrin surface. Because of some small differences with the previous Round 3 puzzle, players will not be able to load in previous work. See the puzzle comments for objective details. Let’s give cancer a good fight!
Residue IE Score (max +500)
Monitors that all PHE, TYR, and TRP residues are scoring well.
Core Existence (max +1640)
Ensures that at least 25% of residues are buried in the core of the designed binder.
Residue Count (max +275)
Penalizes extra residues inserted beyond the starting 60, at a cost of 55 points per residue. Players may use up to 65 residues in total.
For some reason, the puzzle was working just fine, then suddenly when I wiggle it collapses and does odd things, I triple checked, I don't have any random bands, clashing importance is at full, but it is not wiggling erratically.
figured it out (sort of) was an issue with the sheet
