Tool to create synthetic binding protein partners to a specific protein - Help

Started by JohnWick

JohnWick Lv 1

Dear,
I am looking for a tool to create synthetic binding protein partners to a specific protein, based only on the primary amino acid sequence. Anything similar to this publication would work perfectly: https://pubmed.ncbi.nlm.nih.gov/30660105/

Unfortunately for this publication, authors haven't shared the algorithm or any online tool.

Anyone can help?

Thank you!

LociOiling Lv 1

Foldit has presented many puzzles that are similar to what you're trying to do.

At the moment, the Design of the Month: March 2023 shows a monkeypox H3 binder design. There's a target that's mostly locked in place, except for a few sidechains. Then there's a three-helix bundle that's the designed binder.

The 3d viewer on the website gives you an idea, but you'll need to install Foldit to see the puzzle in depth, and the many Foldit tools available.

There have been many similar binder puzzles in the past. Unfortunately, there aren't any new ones at the moment. The monkeypox H3 series of puzzles was the most recent.

The current version of Foldit doesn't let you go back to old puzzles. After puzzles expire, you won't be able to load them in Foldit unless you have played them. (Just opening a puzzle counts as playing.) So there's not a good option for seeing the many binder puzzles of the past. The Foldit week does contain screenshots of some designs, however.

If you have your own target protein in mind, there a few options.

There's a standalone version of Foldit, which lets you load your own proteins from a PDB file and use the Foldit tools on them. More complex puzzles like binders of course require additional configuration files. There is not much publicly available documentation on advanced puzzle setup. Most of the configuration files for the game version of Foldit are encrypted, so previous puzzle won't be much help there.

The game version of Foldit has a "private puzzles" feature, but I don't know if it's working yet. The current version of Foldit was released last September, and I believe private puzzles were still on the "to do" list.

The last option is to convince a Foldit researcher to create a puzzle for your target protein. There have been many suggestions of this type in the past, but I'm not sure if these suggestions resulted in any puzzles.

jeff101 Lv 1

Foldit has its own AlphaFold tool that can take the primary amino acid sequence for your specific protein and propose a 3D structure for it. Foldit's AlphaFold also gives a confidence score for its proposed structure. Many puzzles have used the rule of thumb that structures with >80% confidence are more likely to fold as predicted.

When a puzzle is for two different proteins binding to each other, usually one has a well-known and mostly fixed structure while the other can be designed and can use AlphaFold to help make a good design. I don't think we've had any puzzles where players can run AlphaFold on both members of a pair of proteins (unless both proteins are identical, as in Foldit's many Symmetry Puzzles).