29 April 2015

Tenth Annual Fragment-based Drug Discovery Meeting...Teddy's Thoughts

Dan posted his thoughts here.  Like Dan, CHI put me to work: I chaired the first session in PPIs, co-taught (with Dan) our award winning FBDD course to 22 attendees (a new high which I think shows that interest in FBDD is still growing), moderated a breakfast roundtable on kinetics and thermodynamics,  judged posters.  All of this during weather which made the natives shiver, and me feel like spring is really here (64F and cloudy).  

First off, there was live tweeting of talks by me and a few others: @iceobar, @moleculesmith, and others.  Beware that the Dubai Diamond Conference was also going on that week.  

In the PPI track, just as last year, fragments were a key component to various projects.  Mark McCoy, Merck (and he taught me more about NMR than just about anyone, whether he will admit it or not) gave a great talk on HDM2-p53.  I took away a few things from his talk which I really liked.  Merck (legacy S-P) really relies on NMR structural information: HSQC-based screening, NMR-based Ki,  and NMR-driven docking.  I was particularly intrigued with the NMR-driven docking because they were able to generate 80+ models with a 75% success rate that was confirmed by X-ray (once that was enabled).  They were forced down this path because they went 2 years without a X-ray structure. 

Joe Patel of AZ talked on SOS-RAS.  What I liked was that AZ uses a modified Voldemort Rule (which Harren Jhoti incorrectly attributes to me; I am the Boswell to Rod Hubbard's Johnson): HAC less than/equal20, cLogP less than5, less than3 rings, less than5 rot bonds, less than 3 HBD, and less than 5 HBA.  Their initial X-ray screening ended up at a wall, so they went to a covalent approach. 

Troy Messick of the Wistar gave a nice talk on using fragments and SBDD to drug an "undruggable" target.  I think this is exactly this is exactly the kind of success that has led FBDD to be ubiquitous these days.  I have to admit I have and am working with the Wistar on the NMR component of their screening, so I may be biased. 

I won't go into the various talks from the FBDD track,  However, echoing Dan this is really a great conference.  My main take home themes is that FBDD is really mainstream.  It's no longer the red headed stepchild to other hit generation processes (apologies to my ginger friends).  Biophysics is also seeing a huge growth, having grown up with FBDD, but really finding a lot more uptake outside of that space.  Next week I will post summaries of roundtables and some useful information. 

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