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Sequence symmetry during FastDesign for repeat protein design

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Sequence symmetry during FastDesign for repeat protein design

I want to design a repeat protein that self-assembles into a designed structure. As a result, I want each repeat to acquire the same sequence after the FastDesign mover. Is it possible that during FastDesign mover, all repeats are mutated the same way? Is there any Taskoperation (or mover) I can call to set up such a constraint?

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Tue, 2022-09-06 21:02

The simplest approach is probably to add in a ResidueTypeLinking constraints with the FavorSymmetricSequence mover. (Remember to add the res_type_linking_constraint term to your score function.) Note that this only affects the score -- mutations will be considered independently of each other. This means that if you add in too high a penalty/weight, your structure won't mutate at all, because any energy gains in mutation will be overwhelmed by the energy loss from making things non-symmetric. My recommendation would be to try a protocol where you call FastDesign multiple times, ramping up the res_type_linking_constraint weight for each run.

There's also the SetupForSequenceSymmetryMover and KeepSequenceSymmetry framework, which should do the sampling in a sequence symmetric fashion. That might be a bit harder to get to work with the FastDesign mover, but I think it might work out-of-the box if you pass FastDesign the KeepSequenceSymmetry task operation.

Wed, 2022-09-07 09:19