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Generate De Novo Binders

De novo binder design using AlphaFold2 to generate binders with 10-100% experimental success rate for challenging targets such as cellular receptors, allergens, de novo designed proteins, and CRISPR-Cas9.

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Experimental Validation

BindCraft was tested on 12 diverse, challenging, and therapeutically relevant targets.
AntigenTypeLowest Measured KdExperimentally Confirmed Binders / Tested Designs
PD1Cellular Receptor<1 nM*13 / 53 (24.5%)
PD-L1Cellular Receptor615 nM*7 / 9 (77.8%)
CD45Cellular Receptor15 nM4 / 16 (25%)
CLDN1Cellular Receptor<200 nM6 / 7 (85.7%)
IFNAR2Cellular Receptor260 nM3 / 9 (33.3%)
DerF7Common Allergen13 nM4 / 10 (40%)
DerF21Common Allergen793 nM*4 / 7 (57.1%)
BetV1Common Allergen120 nM2 / 7 (28.6%)
SpCas9Multi-domain Nuclease267 nM6 / 6 (100%)
CbAgoMulti-domain Nuclease5 nM2 / 12 (16.7%)
BBF-14De novo21 nM6 / 11 (54.5%)
Sas6Structural5.7 µM3 / 9 (33.3%)
  • = estimated Kd due to poor fit

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Troubleshooting no successful designs

BindCraft works by filtering out designs as it generates them against a series of metrics including pLDDT, pTM, ipTM, and iPAE, to ensure high quality final designs. However, this means that it can take many hours to find any binders which pass all the filters, and some targets never find a suitable binder. By default, we run all BindCraft jobs for 8 hours before stopping them, but you can adjust this up to 48 hours. BindCraft is sensitive to initial hotspots. If your job fails to find any successful designs, please try changing the hotspot area. If your designs still fail, you can try using the “relaxed” filters or setting custom values for certain filters. Target structures are limited to ~600 residues due to compute constraints. Please trim your target protein down to this length.

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Rosetta Scoring

BindCraft relies on Rosetta for scoring and some utilities. We’ve created a version of BindCraft without Rosetta, and offer that by default. If you have a Rosetta license, please let us know and we’ll work with you to enable Rosetta-based scoring. Try BindCraft