Dynamic Profiling and Binding Affinity Prediction of NBTI Antibacterials against DNA Gyrase Enzyme by Multidimensional Machine Learning and Molecular Dynamics Simulations.

ABSTRACT: Bacterial type II topoisomerases are well-characterized and clinically important targets for antibacterial chemotherapy. Novel bacterial topoisomerase inhibitors (NBTIs) are a newly disclosed class of antibacterials. Prediction of their binding affinity to these enzymes would be beneficial for de novo design/optimization of new NBTIs. Utilizing in vitro NBTI experimental data, we constructed two comprehensive multidimensional DNA gyrase surrogate models for Staphylococcus aureus (q² = 0.791) and Escherichia coli (q² = 0.806). Both models accurately predicted the IC₅₀s of 26 NBTIs from our recent studies. To investigate the NBTI's dynamic profile and binding to both targets, 10 selected NBTIs underwent molecular dyna

SUBMITTER: Kokot M 

PROVIDER: S-EPMC11044241 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature