THINK Docking of some known Drugs

We hand selected a number of marketed drugs including proteases inhibitors.

We used the 1093 (5RF3) crystal structure with 3 centre pharmacophore docking targeting residues that have strong interactions in the non-covalent crystal complexes: (41),(44),(140),(142),(143),(144),(163),(166),(189).

An SD file of My selection is available but as yet I have failed to upload any SD files (SERVER 500 error).

I am checking the availability and usage rights on drug databases (I used to have a copy of the Chapman & Hall Dictionary of Drugs).

We have also been looking at docking into human proteases in order to design in selectivity. These results are available on request. At present although visitors may submit molecules for docking against 1093 via our website, counter screening against human proteases is not yet online. (Please contact me for a free account for non-commercial use).

Keith, great stuff. Can you dock drugs such as Palvix, especially one of its metabolites?

I checked these using our E-services on by just cutting and pasting the SMILES. In principle, you can do the same but for a free service you’d need to use the contact us page to so that I can set it up.

Palvix itself is not predicted to bind using our 1093 non-covalent query (the docking seeks molecules with at least 3 N+Os not localised in one part of the molecule by expecting a 3 centre pharmacophore to extend over much of the molecule). The thioester metabolite is predicted to bind weakly (-4.5) and the pyrrole derivative does better (-17.4). However, there are several marketed drugs which are predicted to do better …

Although the E-service includes an automated De Novo derivative capability this isnt included as part of the Covid-19 service.