FIGURE

Fig. 5

ID

ZDB-FIG-210617-11

Publication

Hosseinzadeh et al., 2021 - Anchor extension: a structure-guided approach to design cyclic peptides targeting enzyme active sites

Other Figures

All Figure Page

Back to All Figure Page

Fig. 5

Improvements in scoring, structure sampling, and binding orientation sampling should increase design binding affinity and selectivity.

a Conformational sampling of des1.1.0 (Source Data are provided as a Source Data file). Inset: Overlay of the crystal structure (gray) and the best scoring model (green). The CA atom of the SHA anchor is shown as sphere for reference. b Overlay of predicted binding orientation from our large-scale parallel docking (dark gray) with crystal structure (light gray) of des1.1.0 shows that docking can accurately predict orientation of key residues at the interface. c Despite improvement of the IC₅₀ values over the original SHA anchor (pink square), most designs follow the same trend as SHA; binding slightly more tightly to HDAC6 over HDAC2. Different colors show results of designs from different methods (blue = method 1, orange = method 2, green = method 3, purple = method 4). TSA (Trichostatin A, red diamond), a pan-HDAC inhibitor, is shown as a control. d Comparison of computational conformational sampling for a structured (gray) and a functional (purple) macrocycle shows a much deeper energy gap for structured macrocycle compared to the functional macrocycle (Source Data are provided as a Source Data file).

Expression Data

Expression Detail

Antibody Labeling

Phenotype Data

Phenotype Detail

Acknowledgments

This image is the copyrighted work of the attributed author or publisher, and ZFIN has permission only to display this image to its users. Additional permissions should be obtained from the applicable author or publisher of the image. Full text @ Nat. Commun.