New poll: fragment libraries in 2023

The quality of a fragment hit depends on the quality of the library. Virtual screens can be done with billions of compounds, but if you’re going to build a physical library you need to be pickier. Researchers today are increasingly avoiding pathological molecules such as PAINs, but even sticking to “reasonable” molecules leads to choice overload.

 

So for those building or refurbishing their libraries, Practical Fragments launches a new poll. It’s been almost five years since we’ve asked readers about their libraries, and the current poll is our longest yet, with six questions.

 

The first three questions focus on size: how large is your fragment library and what are the minimum and maximum number of heavy atoms in each fragment.

 

Next, we ask about whether you include chiral molecules in your library, and whether these are present as enantiomerically pure compounds or racemates.

 

Chiral compounds can introduce synthetic challenges which may impede hit follow-up, so our next question asks whether you consider synthetic tractability before adding fragments to your library.

 

Finally, building a proper fragment library requires considerable time and resources, so you want to take good care of it. Our last question probes how you store your fragment library. Note that this question asks about your working library, the one that you screen and access on a regular basis, not the master stocks which may be squirreled away as solids in the deep freeze.

 

Please vote on the right-hand side of the page. If you have multiple fragment libraries (perhaps one for crystallographic screening and another for biochemical screening) feel free to vote for each; you need to press "Finish Survey" at the end.

 

There are, of course, more complex elements to library design that can’t be captured in simple multiple-choice polls. For example, we’ve written previously about the importance of function rather than functional groups, and the types of rings found in approved drugs. If you have opinions about these or other subjects, please share.

 

The poll was already long so we decided not to ask about library vendors, which we addressed in 2018. On this topic too, please feel free to share your thoughts.

 

Happy voting!