Extended Data Fig. 10: AlphaFold3 retrospectively predicts binders.
From: Atomically accurate de novo design of antibodies with RFdiffusion
A) ipTM distributions of design VHH libraries against 4 targets. Red lines indicate validated binders. B) ROC curve demonstrating strong retrospective predictive power of AF3 at discriminating designed VHH binders from non-binders (AUC = 0.86). Note though that this plot is dominated by influenza HA binders, which are more numerous than confirmed binders to SARS-CoV-2 RBD and TcdB. C-D) Similar retrospective analyses of TcdB scFv binders. These binders were assembled combinatorially from structurally similar “parent” designs. The successfully-binding combined designs have significantly higher AF3 ipTM scores than the parent designs from which they emanate (C, 6 binders from 12 parent designs; two-sided Students t-test; p = 0.0025), and from the parental library as a whole (D). These analyses indicate the utility of AF3 for antibody design filtering.
