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Updated: Jul 11, 2026
08:35
Achieving Efficient Fragment Screening at XChem Facility at Diamond Light Source
Published on: May 29, 2021
Fragment-based screening using X-ray crystallography and NMR spectroscopy
Harren Jhoti1, Anne Cleasby, Marcel Verdonk
1Astex Therapeutics, 436 Cambridge Science Park, Cambridge CB4 0QA, United Kingdom.
Current Opinion in Chemical Biology
|September 14, 2007
Summary
Fragment-based screening accelerates drug discovery by analyzing simple molecule interactions with protein targets. This method enhances understanding of drug-target binding, leading to more efficient development of new medicines.
Area of Science:
- Biochemistry
- Structural Biology
- Medicinal Chemistry
Background:
- Fragment-based screening is a key drug design approach.
- It rapidly explores protein active site complementarity with small molecules.
- Advances in structural and NMR techniques enhance its utility.
Purpose of the Study:
- To highlight the value of fragment-based screening in drug design.
- To discuss recent technological advancements improving fragment screening.
- To explore the impact of these methods on understanding protein-fragment interactions.
Main Methods:
- Utilizing structural methods like X-ray crystallography.
- Employing Nuclear Magnetic Resonance (NMR) screening with advanced probes.
- Analyzing protein-fragment binding site complementarity and affinity data.
Main Results:
- Improved data collection and analysis in X-ray crystallography.
- Expanded capabilities in NMR screening, including (19)F NMR.
- Greater knowledge of protein-fragment interaction chemical diversity, structures, and energetics.
Conclusions:
- Fragment-based screening significantly reduces drug discovery timelines.
- Detailed analysis reveals unexpected similarities between fragments and active sites.
- This enhances pharmacophore understanding and enables target reuse.
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