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levitate.bio
Levitate Bio
@levitate.bio
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We're a small software company owned by the Rosetta Commons and dedicated to making easy to use and deploy cloud based protein engineering and molecular modeling software https://levitate.bio/subscribe
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This allows the models to "understand" the cyclic aspect of a cyclic peptide. And it seems to work pretty well! Decent looking designs within < 1Å of the crystal structure and <1nM IC50s. The code and models arent out yet but we look forward to tryin git out.
Figure 3 from the preprint. its a 9 panel figure, and the figure caption makes for decent alt text so here it is: (A) AfCycDesign predicted model for design GAB_D8 bound to GABARAP shown as surface, with hotspot residues highlighted in green. (B) Affinity determination of GAB_D8 using SPR. SPR sensorgram from 9-point single-cycle kinetics experiments (5-fold dilution, highest concentration 20 µM). Experimental data are shown in orange and global fits are shown with black lines. The dissociation constant (KD) is also shown on the plot. (C) Superposition of chains E and F from the X-ray crystal structure of GAB_D8 bound to GABARAPL1 and the AfCycDesign model. (D) AfCycDesign predicted model for design GAB_D23 bound to GABARAP shown as surface, with hotspot residues highlighted in green. (E) Affinity determination of GAB_D23 using SPR. SPR sensorgram from 9-point single-cycle kinetics experiments (5-fold dilution, highest concentration 20 µM). Experimental data are shown in pink and global fits are shown with black lines. The dissociation constant (KD) is also shown on the plot. (F) Alignment of chains A and B from the X-ray crystal structure of GAB_D23 bound to GABARAP and the AfCycDesign model. (G) Alignments of GAB_D8 and GAB_D23 macrocycle models to X-ray crystal structures show close matches. (H) Comparison of GAB_D8 and GAB_D23 binding modes in the design models. (I) Competitive AlphaScreen response vs. concentration plot, IC50 from the average of three experiments. Donor and acceptor beads in the assay are bound to GABARAP and GABARAP-binding peptide K1, respectively.
November 21, 2024 at 8:26 PM