Pharmacophore Modelling Using The Aryl Pyrrole Data To Date.

12 Dec
Published by m.robertson


Request for Help

I’ve recently been doing some pharmacophore modelling of some of the OSM and GSK compounds.  I was kindly given access to the Schrodinger Suit Software by Dai Hibbs in the Faculty of Pharmacy here at Sydney.  Unfortunately, my previous experience with the Schrodinger software is rather limited and I’ve never used the Phase application before.  Anyway, I set about getting used to the software again watching all the online tutorials and reading the manuals.  After getting used to the software a nice trend in the data was found and I set about tuning this model.  Unfortunately this is where I’ve reached my limit with this software, other software I have available and my non-existent scripting skills.

I see this as a great opportunity for new people to get involved with this Open Source Drug Discovery project either with a better understanding of Phase, the use of different software packages or manually scripting.

A full account of my work can be found here -  but ideally what I would like to be able to do would be able to take the hits I’ve already found by compounds matching all 5 features then filtering with the following additional features

  • Filter out compounds that contain a nitrogen atom in the area of 6.53, -6.28, 1.52 however favour oxygen atoms here.
  • A size exclusion sphere should be added in the region of 4.53, -5.9, 2.99
  • Filter out the pyrazole core as it appears the a second nitrogen cannot be accommodated at the 2 or the 5 position of the pyrrole.

It'd be great if all of this could be combined into one process.  From my previous experience it should be fairly easy to do this in Pipeline Piolt .  This woul then allow us to screen large databases for vitual hits with limited manual filtering required.