04 December 2008

Great Discussion

Those of who didn't read this link have missed a fabulous discussion buried in the comments.

Mekie started by asking (for a school paper) how widely FBDD is used.

Dan said widely. However, the current economic situation is seeing early technologies (those farthest from making money, like FBDD) getting axed. Exactly what Sunesis did :-(

Mekie followed up with the obvious question. Is it he cost of the biophysical techniques, such as X-ray/NMR/SPR that is the big problem. Would a cheaper technique be better

I jumped in with both feet and unafraid to piss anyone off by saying, "Nope. It's the chemist's hubris."

Then Dan, being the voice of reason, said it is more pragmatism over hubris. Too often weak hits ended up being complete crap and we are paying for that.

Tony G. joined in and said SPR may be the savior of FBDD (highly paraphrased. Go read his comments, quite cogent).

Then Pete joined the party and FBDD can negate the huge advantage in chemical space that Big Pharma has over small companies. He also agreed with Dan and expanded in that FBDD has not really been shown with membrane targets (which are only 50% of all the targets).
My comment about this is, the natural ligands are already fragments (Count the number of heavy atoms in serotonin.) He also says you need structural data and that is not forthcoming for membrane proteins. Hogwash says I. But we can debate that at a later time.

Finally NMR-soul pointed out that FBDD needs an early committment of resources when the chance of failure is the highest.

These were some excellent comments, well worth going in and reading. I think everyone would agree that FBDD practitioners (and can we come up with a cool name already) are also to blame for overselling what FBDD can deliver (I call this the NMR effect for obvious reasons.)

1 comment:

TonyG said...

This is Tony G from the summary above (Tony Giannetti, Genentech Inc.) I wanted to clarify the statement above. I DID NOT say SPR was coming to save us all. In the post the original questioner asked if cost was a major factor in doing fragment work and I ONLY said the SPR was less expensive on a per-well basis than NMR or crystallography, but then go through great pains to point out that all the techniques work pretty well and what you use is often a function of your infrastructure, expertise, and preferences. I've seen too many "Messiah" technologies over the years that didn't lead us all to Nirvana. SPR has some great freatures about it but is by no means better or worse than the other techniques, just different.