FBLD 2012 is about to happen. Although I'll not be there (and not even nearby), I thought that a preview, like the one posted recently for EuroQSAR (which I also didn't go to) might be in order.
Rod Hubbard will kick things off and he always does a great talk. Following his contribution will be three talks from Big Pharma. I've only ever been to one fragment conference and the Big Pharma contributions at that meeting tended to be strategy-heavy and results-light. Hopefully things will have moved on a bit in the last three and a half years...
Were I attending the meeting, I'd be paying particularly close attention to the membrane protein talks (and might even take the opportunity to ask one of the creators of the Rule of 3 how hydrogen bond acceptors are defined when applying Ro3). I would also be trying to learn as much as possible about newer technologies for measuring affinity. Remember that the power of a fragment screening assay is defined by the weakness of the binding that can be detected. Although always desirable, high throughput is a secondary consideration in these assays since one rationale for screening fragments is that one doesn't need to assay as many compounds. Expect to see at least one speaker get reminded that in SPR molecules are 'tethered' rather than 'immobilised'.
Thermodynamics and kinetics provide the focus of a few of the talks and usually one will hear about the benefits of 'enthalpy-driven' binding and slow off-rates. My stock question for those who assert the benefits of binding that is 'enthalpy-driven' is, "how do isothermal systems sense enthalpy changes associated with binding?" and I have also made this point in print. For a fixed Kd reducing the off-rate will also reduce the on-rate and binding kinetics have to be seen in the broader context of distribution. If the binding is faster than distribution then on-rates and off-rates become irrelevant, except to the extent to which they determine Kd.
At a conference like this, I'd have hoped to see something along the lines of 'unanswered questions and unsolved problems'. How predictive are fragment properties of the properties of structurally-elaborated molecules? Just how strong is the correlation of promiscuity with lipophilicity? Is getting structures for protein-ligand complexes still a bottleneck?
So best wishes for an enjoyable and successful meeting. Make sure to test the wits of the speakers with some tough questions. It's character-building for them and loads of fun for everybody else. Meanwhile here in Brasil it is 'imunização para insetos' at my place and I've cooked up a local response to enthalpy optimisation: Termodinâmica Macumba.