New poll: structural information needed for F2L and fragment-finding methods

With elections taking place around the world, Practical Fragments is getting into the action. Our new poll revisits two questions from past years to see how things have changed.

 

Our first question asks, “how much structural information do you need to begin optimizing a fragment?” When we ran this poll back in 2017 a third of respondents needed crystallography to begin a fragment-to-lead campaign, while only a quarter would move forward with SAR only. But when Wolfgang Jahnke, Ben Davis, and I published a review in 2018 about advancing fragments in the absence of crystal structures, we found an abundance of approaches. It will be interesting to see whether these numbers have shifted.

 

Our second question asks what method(s) you use to find and validate fragments. For consistency with previous polls please click every method you use, whether as a primary screening technique or for validation. Please note too that we’ve added cryo-electron microscopy. You can read about these methods below, and if you select “other” please describe in the comments.

 

• Affinity chromatography, AS-MS, capillary electrophoresis, or ultrafiltration
• BLI (biolayer interferometry)
• Computational screening
• Cryo-EM (cryogenic electron microscopy)
  
• Functional screening (high concentration biochemical, FRET, cell-based, etc.)
• ITC (isothermal titration calorimetry)
• Literature or known fragments
• MS (mass spectrometry, native or covalent)
• MST (microscale thermophoresis)
• NMR – ligand detected
• NMR – protein detected
• SPR (surface plasmon resonance)
• Thermal shift (or DSF)
• X-ray crystallography
• Other

 

Please vote on the right hand side of the page; click the vote button for each question. (If you don’t see the poll you may need to (1) turn off private browsing, since the free Crowdsignal version we use for the blog cannot support surveys in this mode or (2) view web version on your phone.)