RosettaCommons / RosettaCommons/RFdiffusion

Possible to specify secondary structure for specific part of a diffused protein without using fold conditioning on defined scaffolds

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Python
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Description

I would like to use RFdiffusion to design an alpha-helical linker between one protein and another protein. Is there a way to specify that a certain part of a design should be alpha-helical without fold conditioning on a specific protein scaffold? My current thought is to use motif scaffolding with the following contig:

'contigmap.contigs=[A1-100/70-150/B1-100/70-150/A101-200]'

Where chain A is the first protein I want to link and chain B is the second. Here, the link to chain B is being inserted in place of a loop in chain A (i.e. primary structure will be ProteinA(first half)-alphaHelicalLinker-ProteinB-alphaHelicalLinker-ProteinA(second half).

I currently cannot see a way to specify that the linker ('contigmap.contigs=[A1-100/70-150/B1-100/70-150/A101-200]') must be alpha helical. Is it possible to do this in an easy way at the command line or do I need to do something janky with a dummy pdb to fold condition on for the linker region?

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Research direction

Start with the motif-scaffolding entry point and the contigmap.contigs command-line option described in the issue, then compare it with fold conditioning. Determine whether linker secondary structure can be specified without a scaffold; done means documenting a supported command-line approach or scoping the required feature.

Written by the indexing model from the issue text.

Assessment

Tech stack
python
Domain
bioinformatics, machine-learning
Issue type
Feature
Difficulty
5/5
Estimated time
Over a week
Activity status
Stale
Clarity
Needs clarification
Newbie friendliness
25/100

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