Using Homology Modeling or AI-Folding with Design for Backbone Structure Re-Design

The sample workflow below illustrates a manual method to design loops with Levitate Bench, which can also be applied to generalized backbone structure re-design.

  1. Edited Sequence
    Generate a FASTA of your starting sequence, then insert/remove a few residues at the spot where you want to lengthen/shorten a loop. an illustration of a sequence with the loops to be deisgned colored
  2. Homology Modeling
    Run this sequence as an input using Homology Modeling or AI Folding to generate models a cartoon depiction of a protein
  3. Design
    Now do sequence design (cycles of Design/Minimize) on your target loop or the loop and neighbor residues to achieve lower total score – this is a sequence optimization given that backbone structure. It can be helpful to model loops from multiple starting conformations geneated by the Homology Modeling or AI Folding tools. a screenshot of the Bench Design action UI
  4. Relax
    To test those designs, run 5-10 Relax reps. If the structure stays relatively static after relax, then the sequence matches the backbone well. If the structure moves after relax, try further design (step 3) or decide if the new backbone is satisfactory. an ensemble of relaxed protein models
  5. Iterate
    A final well-designed loop should stay relatively static after Relax. Sequences that stay static in Relax are good sequences to try experimentally.

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