Ten years ago today Teddy launched Practical Fragments with a simple question about screening methodologies. More than 660 posts later we've returned to that topic several times, most recently in 2016. But before you can start screening you need a fragment library, which is the subject of our new poll.
Back in 2012 we asked readers the maximum size (in terms of "heavy", or non-hydrogen atoms) they would consider for fragments in their library. The results were mostly consistent with the Rule of 3, so beloved by Teddy that he compared it to a powerful wizard.
There has since been a trend toward smaller fragments, driven in part by empirical findings that smaller fragments have better hit rates, in agreement with molecular complexity theory.
At some point, though, ever smaller fragments will mean lower hit rates: fragments that are too small will bind so weakly they will be difficult to detect. And practical issues arise: organic molecules with just a few non-hydrogen atoms are often volatile.
Therefore, we’re revisiting this question: What is the smallest fragment you would put in your library?
As long as we're on the subject of libraries, how many fragments do you have in your primary screening library, or how many do you screen on a regular basis?
Please vote on the right-hand side of the page. If you have multiple fragment libraries (for example one for crystallographic screening and one for biochemical screening) you can respond for each library; you will need to press "vote" after each answer. Please feel free to leave comments too.
Thanks to all of you for making Practical Fragments a success and for your comments over the years – looking forward to the next decade!