The target
Human PD-L1, the IgV domain, taken as chain A of PDB 4ZQK — the solved PD-1/PD-L1 complex. 115 modelled residues, crystal numbering 18-132. Hotspots Ile54, Tyr56 and Met115.
It is a target you can mark your own homework on. Chain B of the same file is PD-1, the natural partner, so the three hotspots are not a guess — they are residues a real binding protein is known to cover. That makes one question answerable here that is usually not: never mind whether these designs are good, did the model aim where it was pointed?
What we put in the form
- Target PDB —
the 4ZQK file, uploaded whole
- Both chains, exactly as it downloads from the PDB. No trimming and no renumbering, so chain A keeps its crystal numbering 18-132 — which is the numbering the hotspot field expects.
- Target chain —
A
- This is what restricts the design to PD-L1. Chain B in the same file is PD-1, and the run ignores it — otherwise the model would be designing into an occupied site.
- Hotspot residues —
54, 56, 115
- Ile54, Tyr56 and Met115 in the file's own numbering. Three is a normal number: enough to aim the binder at one patch, few enough that you have not drawn the interface yourself.
- Binder length min —
50
- A window rather than a fixed number, so the generator chooses within it.
- Binder length max —
70
- The top design came back at 57 residues, in the middle of the window rather than pinned to either end.
- Budget (final candidates) —
5
- How many designs to keep. BoltzGen generated and scored 200 to return these 5, ranked by ipTM — you are seeing the top of a much larger pile. The guided pilot on this page uses 4.
What came back
Read the banner above the table first: every one of these five falls short of the bar, and the banner is right. The pass bar wants pLDDT at or above 80 and none of these reaches it — they run 69.1 to 78.2. Nothing here is a design you would order. What the run did do is aim. The delivered complex puts the binder on Ile54, Tyr56 and Met115 — all three residues we asked for, at 3.8, 2.3 and 3.3 Å — along with Glu58, Arg113 and Tyr123, part of the same face PD-1 itself covers. On a target whose natural partner sits in the next chain of the same file, that is checkable rather than asserted, and it is what a pilot is for: the epitope is reachable, so a bigger run is worth paying for. Four of the five also refold to under 1.5 Å of the pose they were designed in, the tightest at 0.51 Å. It ran 82 minutes, past the 15-to-60 range quoted higher up this page: 200 designs against a 115-residue target is the heavy end of a pilot. The charge follows the compute actually used, so it landed just under the estimate rather than over.