3zlx Citations

The use of virtual screening and differential scanning fluorimetry for the rapid identification of fragments active against MEK1.

Abstract

We report the analysis of an in-house fragment screening campaign for the oncology target MEK1. The application of virtual screening (VS) as a primary fragment screening approach, followed by biophysical validation using differential screening fluorimetry (DSF), with resultant binding mode determination by X-ray crystallography (X-ray), is presented as the most time and cost-effective combination of in silico and in vitro methods to identify fragments. We demonstrate the effectiveness of the VS-DSF workflow for the early identification of fragments to both 'jump-start' the drug discovery project and to complement biochemical screening data.

Articles citing this publication (5)

  1. An ultrasensitive high throughput screen for DNA methyltransferase 1-targeted molecular probes. Fagan RL, Wu M, Chédin F, Brenner C. PLoS ONE 8 e78752 (2013)
  2. An Automated Microscale Thermophoresis Screening Approach for Fragment-Based Lead Discovery. Linke P, Amaning K, Maschberger M, Vallee F, Steier V, Baaske P, Duhr S, Breitsprecher D, Rak A. J Biomol Screen 21 414-421 (2016)
  3. Enrichment of chemical libraries docked to protein conformational ensembles and application to aldehyde dehydrogenase 2. Wang B, Buchman CD, Li L, Hurley TD, Meroueh SO. J Chem Inf Model 54 2105-2116 (2014)
  4. Is It Reliable to Use Common Molecular Docking Methods for Comparing the Binding Affinities of Enantiomer Pairs for Their Protein Target? Ramírez D, Caballero J. Int J Mol Sci 17 (2016)
  5. Flavonoids as CDK1 Inhibitors: Insights in Their Binding Orientations and Structure-Activity Relationship. Navarro-Retamal C, Caballero J. PLoS ONE 11 e0161111 (2016)