Fragment-based drug design plays an important role in drug discovery. Protein-observed NMR experiments with isotopically labeled samples are used to probe target-ligand interactions and map the ligand-binding sites. Here, we present a protocol to perform fragment screening using NMR spectroscopy. We describe steps for producing ^(15)N-labeled Kirsten rat sarcoma viral oncogene homolog (KRAS) G12D protein, fragment screening using ¹H-^(15)N-heteronuclear single quantum coherence (HSQC)...
[NMR paper] Fragment-based screening by protein-detected NMR spectroscopy
Fragment-based screening by protein-detected NMR spectroscopy
Fragment-based drug discovery (FBDD) identifies low molecular weight compounds that can be developed into ligands with high affinity and selectivity for therapeutic targets. Screening fragment libraries (
[NMR paper] NMR spectroscopy of the main protease of SARS-CoV-2 and fragment-based screening identify three protein hotspots and an antiviral fragment
NMR spectroscopy of the main protease of SARS-CoV-2 and fragment-based screening identify three protein hotspots and an antiviral fragment
The main protease (3CLp) of the SARS-CoV-2, the causative agent for the COVID-19 pandemic, is one of the main targets for drug development. To be active, 3CLp relies on a complex interplay between dimerization, active site flexibility, and allosteric regulation. The deciphering of these mechanisms is a crucial step to enable the search for inhibitors. In this context, using NMR spectroscopy, we studied the conformation of dimeric 3CLp from the...
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[NMR paper] Recombinant Kinase Production and Fragment Screening by NMR Spectroscopy.
Recombinant Kinase Production and Fragment Screening by NMR Spectroscopy.
Related Articles Recombinant Kinase Production and Fragment Screening by NMR Spectroscopy.
Methods Mol Biol. 2016;1360:35-46
Authors: Han B, Ahn HC
Abstract
During the past decade fragment-based drug discovery (FBDD) has rapidly evolved and several drugs or drug candidates developed by FBDD approach are clinically in use or in clinical trials. For example, vemurafenib, a V600E mutated BRAF inhibitor, was developed by utilizing FBDD approach and approved by...
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10-27-2015 12:33 PM
Target immobilization as a strategy for NMR-based fragment screening: comparison of TINS, STD, and SPR for fragment hit identification.
Target immobilization as a strategy for NMR-based fragment screening: comparison of TINS, STD, and SPR for fragment hit identification.
Target immobilization as a strategy for NMR-based fragment screening: comparison of TINS, STD, and SPR for fragment hit identification.
J Biomol Screen. 2010 Sep;15(8):978-89
Authors: Kobayashi M, Retra K, Figaroa F, Hollander JG, Ab E, Heetebrij RJ, Irth H, Siegal G
Fragment-based drug discovery (FBDD) has become a widely accepted tool that is complementary to high-throughput screening (HTS) in developing...
Protocol to perform fragment screening using NMR spectroscopy
Linear Mode
