Start from the structure

The structure is a VHH, a single-domain antibody fragment, bound to the ectodomain of transferrin receptor 1. The receptor sits on the cells that line the brain's blood vessels, which is why a binder to it is worth having; the VHH is the chain to redesign, and the receptor is the reason its binding loops must stay where they are.

TfR1 with a VHH

Chain	Protein	Residues	In the design
A	Transferrin receptor 1	636	Kept whole, seen by the model
B	VHH	125	Redesigned

The model will see both chains and write a new sequence for chain B alone. Chain A is fixed residue for residue, so every contact across the interface is part of what the model conditions on. In the Sequence lab this is the Structure step: load a PDB entry, an AlphaFold DB model or a file, then choose the chains to design.

Next: Residues Read the docs →