Publications by authors named "Sondos Musleh"
The NLRP3 inflammasome is a key target for drug discovery due to its implication in a range of inflammation-related diseases. In this work, we identify new inhibitors of the NLRP3 inflammasome via a hierarchical virtual screening strategy using molecular similarity, docking and MD simulation. The most potent inhibitors identified from a subsequent biological assay (IC of 1 - 4 μM) feature a sulfonamide group, a motif known to favour NLRP3 inhibition, in conjunction with an indole, benzofuran or tricyclic 6,7-dihydro-5H-indeno[5,6-b]furan ring, yielding novel scaffolds.
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- Carbohydrates play a crucial role in molecular recognition and signaling, and this study investigates the use of absolute binding free energy (ABFE) calculations to evaluate how well different carbohydrate ligands bind to the lectin protein concanavalin A.
- The researchers found that ABFE calculations accurately predicted binding affinities and efficiencies for various carbohydrate sizes, with a minimal average error compared to direct experimental measurements using microcalorimetry.
- Despite some challenges in conformational sampling of these ligands, the study highlights the ABFE method’s potential as a valuable tool for understanding carbohydrate-protein interactions, which could aid in the development of new therapeutics, vaccines, and diagnostics.
The CHK1 kinase plays a pivotal role in the DNA damage response pathway. Hence, inhibition of CHK1 appeared as a promising strategy to overcome the resistance problem of chemotherapeutic agents resulting from the overexpression of CHK1 that enables cancerous cells to repair their chemotherapy-induced DNA damage. In this study, different computational drug design techniques were employed to identify new CHK1 inhibitors targeting its allosteric pocket.
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