Fragment Based Drug Discovery
Fragment Based Drug Discovery - Related Videos
01:26
Drug Discovery: Overview
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2023
Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
07:18
Natural Product Discovery with LC-MS/MS Diagnostic Fragmentation Filtering: Application for Microcystin Analysis
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Cited by 11 •
2019
Diagnostic fragmentation filtering, implemented into MZmine, is an elegant, post-acquisition approach to screen LC-MS/MS datasets for entire classes of both known and unknown natural products. This tool searches MS/MS spectra for product ions and/or neutral losses that the analyst has defined as being diagnostic for the entire class of compounds.
06:26
Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery
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Cited by 7 •
2021
Monitoring changes in the melting temperature of a target protein (i.e., thermal shift assay, TSA) is an efficient method for screening fragment libraries of a few hundred compounds. We present a TSA protocol implementing robotics-assisted nano-Differential Scanning Fluorimetry (nano-DSF) for monitoring intrinsic tryptophan fluorescence and light back-scattering for fragment screening.
07:50
Facilitating Drug Discovery: An Automated High-content Inflammation Assay in Zebrafish
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Cited by 39 •
2012
Here we describe a novel high-content chemically induced inflammation assay aiming at the identification of immune-modulatory bioactives. We have successfully combined automated microscopy with custom developed software scripts enabling automated quantification of the inflammatory response as well as further data processing, analysis, mining, and storage.
02:31
Habitat Fragmentation
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2020
Habitat fragmentation describes the division of a more extensive, continuous habitat into smaller, discontinuous areas. Human activities such as land conversion, as well as slower geological processes leading to changes in the physical environment, are the two leading causes of habitat fragmentation. The fragmentation process typically follows the same steps: perforation, dissection, fragmentation, shrinkage, and attrition. Perforation and dissection often occur during the initial stages of...
FAQs
Fragment molecules typically make weak interactions with proteins, so binding may not be apparent through activity measurements alone. Biophysical assays provide a way to detect these interactions directly, while structural methods can clarify how a fragment occupies a target site. This evidence helps distinguish genuine binding events from unsuitable screening hits before medicinal chemistry optimization begins.
Small fragments represent compact chemical structures that can be screened as a library, allowing researchers to survey chemical space efficiently. Their size also helps expose binding sites that larger compounds may miss. These features make fragment screening useful for discovering starting points that may not emerge from conventional searches centered on larger molecules.
Medicinal chemists can improve an initial fragment hit through three structure-guided strategies: growing it into additional regions of a binding site, linking it with another fragment, or merging compatible fragment features. These changes are intended to strengthen binding and improve selectivity, converting a weak starting interaction into a more useful lead for further development.
Structural information shows how a fragment is positioned within a protein binding site and provides a basis for deciding which chemical changes are reasonable. In chemistry-led optimization, that information guides growing, linking, or merging decisions rather than relying only on the fragment’s initial binding signal. The result is a more informed path toward affinity and selectivity.
A typical workflow begins by screening a library of small fragments against a biological target. Researchers then confirm binding with biophysical assays and use structural methods such as X-ray crystallography to examine the interaction. The confirmed fragment hits become starting points for medicinal chemistry, where researchers grow, link, or merge them during lead optimization.
This approach is useful when researchers need chemically efficient starting points for structure-based design and lead optimization. Fragment-derived leads can help reveal target binding sites that larger compounds may overlook, then provide scaffolds for improving potency and selectivity. In chemistry research, the method connects biophysical detection, protein structure, and iterative compound design.