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1999: Tie2 Binder Design: Round 4
Status: Closed


Name: 1999: Tie2 Binder Design: Round 4
Status: Closed
Created: 05/26/2021
Points: 100
Expired: 06/04/2021 - 23:00
Difficulty: Intermediate
Description: Design a protein to bind to the Tie2 receptor! We saw lots of great designs in the previous Round 3 puzzle, so this puzzle is set up just the same. Try to max out the Contact Surface Objective by using sidechains that pack closely against the target binding site!

Tie2 is a human protein that helps to regulate the maintenance and growth of blood vessels throughout the body. Normally, the Tie2 receptor binds a growth factor called angiopoietin, a signaling molecule that triggers the growth of new blood vessels. However, Tie2 overactivity has been implicated in several types of cancer, since rapidly-growing tumors require lots of new blood vessels to provide nutrients. We want to design a protein that could bind to Tie2 and block angiopoietin. A successful binder might be useful as a drug to modulate Tie2 activity that is necessary for tumor growth.

In this puzzle, we've presented a section of the target Tie2 protein that normally binds angiopoietin. The backbone and most of the sidechains are frozen, except at the binding site, where flexible sidechains are shown in color. Players can design a new protein that can bind to these sidechains and block angiopoietin. In order to bind the Tie2 target, designs will need to make lots of hydrophobic contacts and satisfy any polar atoms that are buried at the interface. But designs will also need to have lots of secondary structure (helices or sheets) and a large core, so that they fold up correctly! See the puzzle comments for Objective details.
Categories: Design, Overall

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Joined: 11/15/2012
Groups: Foldit Staff

DDG Metric (max +2000)
The predicted binding energy of your design. The goal DDG is -40.0 or less.

Contact Surface Metric (max +2000)
Measures how much of your binder surface is in close contact with the target protein. The goal Contact Surface is 500 or more.

Buried Unsats (max +500)
Penalizes 100 points for each polar atom that cannot make any hydrogen bonds.

Core Existence (max +1500)
Ensures that at least 25 percent of residues are buried in the core of the monomer unit.

Interaction Energy (max +500)
Monitors that all large PHE, TYR, and TRP residues are scoring well.

Ideal Loops (max +500)
Penalizes any loop region that does not match one of the Building Blocks in the Blueprint tool. Use "Auto Structures" to see which regions of your protein count as loops.

SS Design (max +500)
Disabled use of CYS residues.

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Developed by: UW Center for Game Science, UW Institute for Protein Design, Northeastern University, Vanderbilt University Meiler Lab, UC Davis
Supported by: DARPA, NSF, NIH, HHMI, Amazon, Microsoft, Adobe, Boehringer Ingelheim, RosettaCommons