Molecular dynamics simulation of the antifungal N-((5-cyclopropylisoxazol-3-yl)methyl)-3-(2,3-dihydrobenzofuran-5-yl)-N-methylbenzamide binding to Cryptococcus neoformans acetyl CoA synthetase CnAcs1

The molecule, referred to as isoxazole 1, was identified in a high throughput screen for antifungal inhibitors of Cryptococcus neoformans acetyl CoA synthetase using a synthetic lethal phenotypic screen. The Xray crystal structure of the molecule was determined. Molecular dynamics simulations were performed to study the interactions of the inhibitor with the target. Three independent simulations are included in this data set using the Desmond module of Schrodinger software (Schrodinger, LLC, New York, NY, 2024-1) with OPLS 4 force field (56). First, the molecular system of the ligand-receptor complex was built with water molecules in a cubic box via the simple point charge (SPC) method; which was later followed by ions neutralization by the addition of sodium, to balance the net charge of the solvated system. MD simulation was performed for 1000 ns using the Isothermal-isobaric (NPT) ensemble class, where temperature and pressure were reserved at 300 K and 1.01325 bar pressure employing Nose-Hoover temperature coupling and isotropic scaling. Equilibration of the systems and MD simulations were carried out using the default protocol provided in Desmond