Resfile for fixed backbone design

[Anonymous]

Hi Everyone,

When using the fixed backbone design program, is it possible to specify that two residues can only be changed into the same amino acid? For instance, residue 2 can be varied into any amino acid but residue 6 must be changed into whatever residue 2 is changed into.

Thank you!

[Anonymous]

Standard fixbb does not support this; all of the positions are independent of one another. The “symmetry” stuff might support it – are you trying to do symmetric design?

[Anonymous]

> Hi Everyone,
>
> When using the fixed backbone design program, is it possible to specify that two residues can only be changed into the same amino acid? For instance, residue 2 can be varied into any amino acid but residue 6 must be changed into whatever residue 2 is changed into.
>
> Thank you!

Hi Smlewis,

Thanks for your response. I’ll look into the symmetry stuff. Basically, I have a beta-solenoid structure, and I would like the rungs of the solenoid to be stacked. That is, each position on each rung of the solenoid has the same amino acids.

[Anonymous]

I have a homooligomeric tetramer (with a C4 symmetry, lets say A4) and wish to turn it into a hetero dimer of dimers (A2B2) using fixbb design. I don’t have any experience with symmetric design of Rosetta and reading its symmetry manual discourages me as generating the symmetry_definition file for my purpose seems to be very complicated.

Is there any other method (other than symmetric design) to run fixbb in a way that the same mutation simultaneously happens in the multiple protein chains of interest? I know this is almost the same question that dyq asked, I just hope things might have changed since then.

Thanks in advance!

[Anonymous]

One solution I can think of is to use resfile
https://www.rosettacommons.org/manuals/archive/rosetta3.4_user_guide/d1/d97/resfiles.html

But in dyq’s case you need 20 resfiles with each pair of 20 aa in one resfile.
As for the case of msardejani’s, you may need 20×20 resfiles

[Anonymous]

If you can conceptualize things as a dimer of heterodimers, and if you’re not doing major backbone reorganization, you can “cheat” and consider your AB dimer as a single chain. Then it reduces to a simple symmetric homodimer design problem. Especially in fixed-backbone contexts, Rosetta isn’t too picky about the fact that two residues in the same chain aren’t really bonded to each other. It’s not even picky about the fact that multiple residues have the same chain/number PDB designation, (though for resfiles and the like where PDB designations are used that’s a bit tricky).

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