Fragment-Based Screening
Contact Us

Fragment-based screening for comprehensive lead discovery

Fragment-based screening (FBS) is a widely applied method for the discovery of lead molecules in fragment-based lead discovery (FBLD). It has overtaken high throughput screening (HTS) as the most popular method for screening molecules, due to the significantly fewer compounds required for screening and synthesis, resulting in a higher hit rate for screening molecules than traditional screening methods.

FBLD also delivers a higher success rate in generating chemical series with lead-like properties, enabling a dramatically larger chemical structure space with fewer compounds to be explored. The fragment libraries are characterised by the small size of the compounds and a smaller number of candidate molecules. After identifying molecules that may have initial weak-medium affinities for binding to the desired protein targets, these leads are then optimised to obtain medium-strong binding affinities. At each stage, fragment-protein interactions are detected by highly sensitive NMR spectroscopy.

There are a number of biophysical methods used for FBS, of which NMR is the most popular. NMR-based fragment screening is ideally suited for detecting low affinity ligands in primary screens, and it allows the quality control of the screening library which makes this technology superior to many other methods.

Simply put, NMR makes FBS easier in the lead discovery field, by producing high quality hits. Complementary software combined with innovative FBS tools can vastly accelerate data analysis during NMR-based fragment screening, by incorporating all screening data in one place and automating manual processes.

Bruker’s fragment-based screening tool harnesses the power of NMR data by streamlining the entire acquisition-to-analysis workflow. All relevant data, experiment types, compound IDs, reference spectra and other information are automatically collected, stored in a project file and the display shows the relevant data for analysis.