PostEra

Submission DAV-AUT-7eb

Topic automatically created for discussing the designs at:
https://covid.postera.ai/covid/submissions/7eb4e0c3-ee0f-4428-9ff1-98a8556afc9f

Due to a coding error on my part, the PDB submitted with this submission was not properly uploaded. I am providing it for download here!

DAV-AUT-7eb.pdb (471.5 KB)

I will try to fix this error with the site soon. Sorry!

The core has been substantially modified from a tetrahydroquinoline (fragment x0195) to a cyclic aromatic acyl sulfoximine. It is able to interact with Glutamine 129 side chain directly via the carbonyl oxygen of the core, while exposing to the solvent exposed area the sulfoximine oxygen atom.

The left hand side of the binding pocket is more shallow and, to our knowledge, able to accommodate several different structural motifs bulky, sp3 rich motifs.

A set of 200, 7 and 8 membered rings structures derived from the Crystallography Open Database (stripped of major substituents) were rigidly docked to assess the potential fit to this accessory binding pocket.

The 1,4-oxazepine derivative is inspired from the Crystallography Open Database (ref. 1100289) and is able to interact with Methionine 49 side chain and engage in an interaction with Histidine 41.

This work reflect my own scientific vision, I am working pro bono, using vacation time and own resources (IP and computational equipment).