1659: Integrin Antagonist Binder Design
||1659: Integrin Antagonist Binder Design
||04/15/2014 - 23:00
||Help design a protein binder for cancer therapy!
Integrins are cell adhesion receptors that are normally inactive on the surface of cells. Once activated by a ligand, integrins can induce changes in cell cycle, growth factor signaling pathways, cytoskeletal organization, and movement.
Recently, integrins have emerged as a key target in anti-cancer therapy as integrins are involved in promoting tumor metastasis and cancer blood vessel formation. Integrin antagonists have already proven successful in halting invasion and migration of tumors.
We’re asking Foldit players to help design a complete antagonist of integrin Avb3. The core RGD binding motif of the antagonist ligand is preserved, but the rest of the ligand is up to the Foldit players to design a well-folded protein. The loop sequence is based on a high affinity form of the wild type ligand.
In the puzzle, the target integrin heterodimer backbones are frozen, but the side chains are not. The backbone and side chains of the RGD motif loop are frozen, but players can fold and design residues on either side of the loop. Players begin with 50 designable residues.
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