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Rosetta Design: Non-canonical amino acid substrate not accepted

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Rosetta Design: Non-canonical amino acid substrate not accepted

I experience difficulties when submitting an enzyme PDB file with the
substrates AMP and a non-proteinogenic amino acid to the RosettaDesign webserver.
AMP is well accepted but problems arise with the amino acid substrate.

If I name the amino acid with a common identifier such as PHE in PyMOL, its chemical
structure is changed towards e.g. Phe during the design calculations. If I name it differently such as XYX,
the substrate is discarded in calculations. How should I name the molecule so that
it is kept in enzyme design calculations and not chemically modified during the pipeline?

Thanks in advance!

Post Situation: 
Fri, 2023-08-04 00:09
Friedrich Ehinger

The RosettaDesign web server is intended mostly for simple situations, and likely won't be able to handle some more complex protocols (like non-standard non-canonical amino acids).

What you'll likely need to do is to download the Rosetta program from, install it, then run the design process from the command line. If you run Rosetta locally, you should be able to create and use params files which describe the particular noncanonical amino acid you want. (In fact, the most recent version of Rosetta may already have the non-canonical in its database - you'll just need to download and install the rotamer libraries for the amino acid.)

Feel free to ask additional questions along the way, as you have them.

Fri, 2023-08-04 06:41

Thanks for your quick response.
Just for clarification: I do not want to incorporate noncanonical amino acids into the enzyme sequence itself, but want to use a noncanonical amino acid substrate on which the enzyme does catalysis. Is it still necessary to run Rosetta locally?

Fri, 2023-08-04 08:38
Friedrich Ehinger