RosettaCommons / RosettaCommons/RFdiffusion

How to redesign interface residues to enable binding to a homolog?

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Dominant language
Python
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Description

I have a question in protein design. I have a complex consisting of chains A and B. Now, I also have a homolog of chain A, called A'. I want to design a new protein, B', such that A' and B' can bind to each other. Most of the amino acids in B' should remain the same as in B; only the interface residues of B should be changed as needed to enable binding with A'. Essentially, I can only use the structure of B to design a B' that is similar to B, modifying only the interface residues to achieve binding with A'. Is there a method for doing this? I would appreciate any suggestions or advice.

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Research direction

The issue names no files, tests, or entry points. Clarify with maintainers whether this is intended as a new RFdiffusion workflow or a general design question, then establish the expected inputs, interface-residue constraints, and validation criteria before identifying an implementation location.

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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
20/100

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