Discovery of the Novel Inhibitor Against New Delhi Metallo-β-Lactamase Based on Virtual Screening and Molecular Modelling
Abstract
1. Introduction
2. Results and Discussion
2.1. Virtual Screening Analysis
2.2. Nitrocefin Assay
2.3. Antibacterial Activity Assay
2.4. The Potential Binding Mode of Compound ZINC05683641 with NDM-1
2.5. Confirmation of the Binding Mode in the Complex
2.6. Identification of the Competitive Inhibition Mechanism
3. Method and Computation
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Ligands | Structure | Binding Affinity (kcal/mol) | IC50(μM) |
---|---|---|---|
ZINC00639379 | −10.0 | 207.28 ± 15.51 | |
ZINC03198432 | −9.4 | >300 | |
ZINC25558269 | −9.2 | N/A a | |
ZINC02938448 | −9.2 | >300 | |
ZINC02079077 | −9.2 | 107.68 ± 5.64 | |
ZINC12524283 | −9.1 | >300 | |
ZINC02953923 | −9.1 | >300 | |
ZINC06166781 | −9.1 | >300 | |
ZINC25558273 | −9.0 | >300 | |
ZINC11865709 | −9.0 | >300 | |
ZINC05683641 | −9.0 | 13.59 ± 0.52 | |
ZINC02577071 | −9.0 | >300 | |
ZINC06421319 | −8.9 | N/A | |
ZINC04218138 | −8.9 | N/A | |
ZINC20115378 | −8.8 | >300 | |
ZINC25558691 | −8.8 | N/A | |
ZINC25694564 | −8.8 | N/A | |
ZINC01799114 | −8.8 | >300 |
Meropenem | ZINC05683641 | Meropenem (+64 μg/mL ZINC05683641) | Meropenem (+128 μg/mL ZINC05683641) | |
---|---|---|---|---|
MIC (μg/mL) | 32 | >512 | 8 | 8 |
FICI | - | - | 0.375 | 0.50 |
Energy Components (kcal/mol) | WT | W93A | H250A |
---|---|---|---|
ΔEele | −12.12 ± 0.96 | −14.11 ± 0.75 | −7.23 ± 1.12 |
ΔEvdw | −38.05 ± 1.15 | −35.43 ± 0.54 | −34.34 ± 1.18 |
ΔEMM | −50.17 ± 1.20 | −49.54 ± 1.12 | −41.57 ± 1.34 |
ΔGsol | 23.21 ± 0.92 | 24.53 ± 0.85 | 19.27 ± 1.13 |
ΔGbind | −26.96 ± 0.88 | −25.00 ± 0.56 | −22.30 ± 0.99 |
KA | 4.17 ± 1.02 | 3.05 ± 0.83 * | 2.15 ± 0.88 * |
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Wang, X.; Yang, Y.; Gao, Y.; Niu, X. Discovery of the Novel Inhibitor Against New Delhi Metallo-β-Lactamase Based on Virtual Screening and Molecular Modelling. Int. J. Mol. Sci. 2020, 21, 3567. https://doi.org/10.3390/ijms21103567
Wang X, Yang Y, Gao Y, Niu X. Discovery of the Novel Inhibitor Against New Delhi Metallo-β-Lactamase Based on Virtual Screening and Molecular Modelling. International Journal of Molecular Sciences. 2020; 21(10):3567. https://doi.org/10.3390/ijms21103567
Chicago/Turabian StyleWang, Xiyan, Yanan Yang, Yawen Gao, and Xiaodi Niu. 2020. "Discovery of the Novel Inhibitor Against New Delhi Metallo-β-Lactamase Based on Virtual Screening and Molecular Modelling" International Journal of Molecular Sciences 21, no. 10: 3567. https://doi.org/10.3390/ijms21103567
APA StyleWang, X., Yang, Y., Gao, Y., & Niu, X. (2020). Discovery of the Novel Inhibitor Against New Delhi Metallo-β-Lactamase Based on Virtual Screening and Molecular Modelling. International Journal of Molecular Sciences, 21(10), 3567. https://doi.org/10.3390/ijms21103567