Cosolvent Sites-Based Discovery of Mycobacterium Tuberculosis Protein Kinase G Inhibitors
- Burastero, Osvaldo
- Defelipe, Lucas Alfredo
- Gola, Gabriel Francisco
- Tateosian, Nancy Liliana
- Lopez, Elias Daniel
- Martinena, Camila Belen
- Arcon, Juan Pablo
- Dodes Traian, Martín Miguel
- Wetzler, Diana Elena
- Bento, Isabel
- Barril, Xavier
- Ramirez, Javier Alberto
- Marti, Marcelo Adrian
- Maria, Garcia Alai
- Turjanski, Adria
DOIAbstract
Computer-aided drug discovery methods play a major role in the development of therapeutically important small molecules, but their performance needs to be improved. Molecular dynamics simulations in mixed solvents are useful in understanding protein-ligand recognition and improving molecular docking predictions. In this work, we used ethanol as a cosolvent to find relevant interactions for ligands toward protein kinase G, an essential protein of Mycobacterium tuberculosis (Mtb). We validated the hot spots by screening a database of fragment-like compounds and another one of known kinase inhibitors. Next, we performed a pharmacophore-guided docking simulation and found three low micromolar inhibitors, including one with a novel chemical scaf...
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