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Dock cyclic peptide with non-canonical amino acids to protein target using rosetta flexpepdock?

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Dock cyclic peptide with non-canonical amino acids to protein target using rosetta flexpepdock?
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Dear Rosetta users,

Is it possible that we could use Rosetta flexpepdock to dock a cyclic peptide (backbone cycle, disulfide cycle, or chemical linker cycle) with non-canonical amino acids to protein target?

It seems we could model the structures for such cyclic peptide with non-canonical amino acids using Rosetta, but I am not sure their docking methods.

If not, could you please recommend a docking program in Rosetta or other software for this application?

Thanks!

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Mon, 2023-09-11 23:34
lei

Hallo Lei,

I had a similar problem and in my experience, FlexPepDock cannot handle peptidic macrocycles with NCAA. Instead, I used the anchor extension approach like in https://www.nature.com/articles/s41467-021-23609-8 and https://www.pnas.org/doi/full/10.1073/pnas.2012800118.

Best,

Yasser

Wed, 2023-09-13 00:13
almeida85

Hallo Yasser,

Thank you very much for your kind reply, I really appreciate it.

I will read them and dock as you suggest.

Best,

Lei

Wed, 2023-09-13 19:35
lei