No technique is dominant, though SPR and ligand-detected NMR are each used by more than 40% of respondents. Thermal shift assays are also popular, with about one-third of people using them.
X-ray crystallography was used by just under a quarter of respondents, less than computational screening and not much more than reported using protein-detected NMR, which is surprising given the challenges of advancing fragments in the absence of structures.
Some of the other techniques such as ITC are still pretty niche at less than 10%, though it will be interesting to revisit this survey in a couple years and see how things change.
Dan, perhaps one reason crystallography isn't more "popular" in your poll is that the question was what technique is used in "fragment screening". I would bet that most, if not all of us use crystallography in FBLD, but not as the upfront screen. At least, that's how I interpreted the question.
ReplyDeleteThanks - good point. I guess I was thinking of screening broadly defined, but you're right that crystallography is often used only later after a few fragments have been chosen to actively pursue.
ReplyDeleteSo, the follow up poll should be, which method is your primary screen.
ReplyDeleteEchoing the first comment, assembling even a purely generic screeninbg library usually involves an element of computation. When using computational methods to predict affinity, it is usually a good idea to sample different chemotypes since affinity prediction is, despite the occasional claim to the contrary, not generally reliable.
ReplyDeleteHow many answered the poll?
ReplyDelete