This computational study identifies potential IHF inhibitors in plasmid-mediated antibiotic resistance, suggesting novel therapeutic strategies.
Key Points
The study aims to develop a computational model to identify small molecules that inhibit the IHF protein, reducing plasmid-mediated antibiotic resistance.
Developed a 3D-QSAR model using a dataset of 65 anti-plasmid compounds.
Validated the model with leave-one-out cross-validation and Y-scrambling.
Evaluated compounds through pharmacophore clustering and molecular docking at IHF's DNA-binding and allosteric sites.
Conducted 200 ns molecular dynamics simulations to assess the stability of the most promising complexes.
QSAR model showed strong predictive performance with R2 = 0.90.
Allosteric binding energies were more favorable (up to -12.15 kcal/mol) than DNA-binding sites.
Molecular dynamics confirmed stability with lower RMSD fluctuations for allosteric complexes.
Dynamic cross-correlation analysis indicated conformational changes in key residues affected by allosteric binding.
Cite This Study
Saurith-Coronell et al. (2026) studied this question.