Fig. 4: Rescue of Rosetta small-molecule binder designs using LigandMPNN.
From: Atomic context-conditioned protein sequence design using LigandMPNN
a,b, Weak or nonbinding designs made using Rosetta for rocuronium (a) and cholic acid (b) were redesigned using LigandMPNN. Left: sidechain–ligand interactions before and after redesign. The sidechains are predicted to be considerably more preorganized following redesign as indicated by the LigandMPNN amino-acid probabilities, which are colored from red (0) to blue (1). Sidechain atoms except for carbon are color-coded (O, red; N, blue; S, yellow). Right: experimental measurement of binding. In a, flow cytometry of yeast is shown, with the designs following incubation with 1 μM biotinylated rocuronium and streptavidin phycoerythrin. In b, fluorescence polarization measurements of binding to cholic acid–fluorescein isothiocyanate are shown. The error bars show the mean and standard deviations for three LigandMPNN and two Rosetta measurements.
