Fragment-Based Drug Discovery (FBDD) is a powerful strategy used in the development of new therapeutics. Molecular fragments are screened against a target protein, where interactions are typically characterized by a low affinity. Nuclear Magnetic Resonance (NMR) spectroscopy is well-suited to detect weak protein–ligand interactions and is therefore often used in FBDD. However, while NMR is very effective in initial screening, follow-up NMR experiments to measure binding affinities (i.e., KD values) are labor-intensive and time-consuming. To address this challenge, we have developed an innovative SHARPER NMR fragment scoring technique. The high sensitivity of SHARPER NMR dramatically reduces the data acquisition times, allowing faster and more accurate quantification of fragment KD values from ligand titration curves. To further accelerate fragment scoring, a machine learning model was developed that accurately ranks fragment affinities from only two SHARPER titration points. The resulting integrated method, termed “ML-boosted 1H LB SHARPER NMR”, produced significant time savings; using a 600 MHz QCI cryoprobe, KD values of up to 144 ligands in a day could be determined under our conditions, compared with only a handful achievable by traditional approaches. The proposed methodology will shorten the transition from hits to lead compounds, accelerating the drug discovery process by rapidly and reliably evaluating fragment binding, providing informed decision-making in the early stages of FBDD.

Cancer Research Horizons Biosciences Student Placement (Lab based) £23,000 plus benefits Directorate: Research & Innovation Contract: Fixed Term Contract 52 weeks Hours: Full time 35 hours per wee...

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I’m raising money for Stand Up To Cancer to help fund life-saving research. Donate to participate in or simply cheer on the players in a charity football match played at the Garscube sports complex on...

Strategic team efforts. Seamless synergy. Tangible results.  Scientist – Bioscience team, under the leadership of Stuart Farrow £33,700 - £38,150 (dependent on experience) plus benefits (includes up t...

4,000 professionals, 0 days wasted, 1 incredible purpose. Together, we are beating cancer. Principal Scientist – Biochemistry/Enzymology Starting salary: From £50,400-£57,400 per annum depending on ex...