Multiplexed experimental strategies for fragment library screening against challenging drug targets using SPR biosensors

Identification of fragments targeting SMYD3 using highly sensitive kinetic and multiplexed biosensor-based screening

“…The multiplexing and unique experimental design available in the GCI-based biosensor was efficient for fragment library screening. The overall workflow and how it compares to conventional screening projects 6 are illustrated in Fig. 7 .…”

“…The fragment library was comprised of 1056 fragments collated from compound collections at SciLifeLab 10 and FRAGNET ( , a Marie Skłodowska-Curie Action Innovative Training Network (ITN) 2016–2020). 6 Fragments were selected on the basis of key physicochemical properties, including heavy atom count (HAC), molecular weight (MW) and calculated lipophilicity (cLog P ). The selection criteria essentially matched the guidelines put forward by Astex for typical fragments (MW < 300 Da, cLog P < 3, hydrogen bond acceptors (HBA) ≤ 3, hydrogen bond donors (HBD) ≤ 3).…”

“…It allowed us to screen and identify hits in a fragment library, previously found to be useful for identifying hits to challenging targets. 6 …”

Deciphering the Lexicon of Protein Targets: A Review on Multifaceted Drug Discovery in the Era of Artificial Intelligence

“…173 Nuclear magnetic resonance (NMR), surface plasmon resonance (SPR), and X-ray crystallography are all commonly used biophysical methods for this purpose. 174,175 Screening fragment libraries has the advantage of being able to discover novel binding sites on the target protein across a broad chemical space, which is impossible when screening larger, more complex molecules. 173 However, there are several challenges associated with this screening approach, such as the careful selection of fragments, the improvement of their binding affinity and specificity, and the fusion of them into more robust molecules.…”

“…The method involves testing numerous small molecules, or fragments, for their ability to bind to a specific protein . Nuclear magnetic resonance (NMR), surface plasmon resonance (SPR), and X-ray crystallography are all commonly used biophysical methods for this purpose. , Screening fragment libraries has the advantage of being able to discover novel binding sites on the target protein across a broad chemical space, which is impossible when screening larger, more complex molecules …”