Submission Details

Design Rationale:

This design uses the x10324 crystal structure and elaborates the piperidone scaffold of the PET-UNK-fcd64629 design (link: https://postera.ai/covid/submissions/fcd64629-0770-431b-85b8-883f59b970d1) with a nitrile substituent to target the catalytic cysteine. The x10324 crystal structure has been used to set the configurations at C3 (chlorophenyl; S) and C6 (R; cyano) of the piperidone ring and the substituents are cis with respect to each other. A substituent on the carbon next to amide nitrogen in a ring typically adopts an axial orientation. I’ve uploaded a pdb file with the designed structure as it is predicted to bind to the protein in the x10324 crystal structure (although I’ve not attempted to model the covalent bond between sulfur and nitrile carbon).

Download PDB File