Publication: Identification of novel compounds against Acinetobacter baumannii 3-oxoacyl-[acyl-carrier-protein] synthase I (FabB) via comprehensive structure-based computational approaches.
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Date
2023-07-12
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Abstract
Acinetobacter baumannii is one of the most serious opportunistic pathogens according to WHO. The difference
between bacterial and mammalian fatty acid biosynthesis pathways makes FASII enzymes attractive targets in
drug discovery. 3-oxoacyl-[acyl-carrier-protein] synthase I (FabB) from the FAS II pathway catalyze the
condensation of malonyl ACP with acyl-ACP, and elongates the fatty acid chain by two carbons. To investigate
potential inhibitors of the A. baumannii FabB, we used computational approaches including homology modeling,
high-throughput virtual screening, molecular docking, molecular dynamics simulations, and MM-GBSA free
energy calculations. After the high-throughput virtual screening, the resulting ligands were further screened
using the QM-polarized ligand docking (QPLD) and induced fit docking (IFD) approaches. Molecular dynamics
simulations were performed for 100 ns. And according to binding free energy calculations, we have identified
nine compounds with the best binding affinities. Three of these compounds were selected for an additional 1 μs
MD simulation to assess ligand stability. Two of them named L6 and L7 showed promised stability and affinity to
the target. Here, we present novel compounds against A. baumannii FabB via structure-based computational
approaches. These compounds might pave the way for the design of new lead structures and inhibitors for
multidrug-resistant A. baumannii.
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Keywords
Acinetobacter baumannii, 3-Oxoacyl-[acyl-carrier-protein] synthase I, FabB, Computer-aided drug discovery, Molecular dynamics simulation
Citation
Albayrak E., Koçer S., Mutlu Ö., "Identification of novel compounds against Acinetobacter baumannii 3-oxoacyl-[acyl-carrier-protein] synthase I (FabB) via comprehensive structure-based computational approaches.", Journal of molecular graphics & modelling, cilt.124, ss.108565, 2023
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https://hdl.handle.net/11424/291636
https://hdl.handle.net/11424/291636