Discovery of Antibacterial Compounds with Potential Multi-Pharmacology against Staphylococcus Mur ligase Family Members by In Silico Structure-Based Drug Screening
Abstract
:1. Introduction
2. Results
2.1. Hierarchical In Silico SBDS Targeting saMurE
2.2. Growth Inhibition Assay against Staphylococcus epidermidis (S. epidermidis)
2.3. MDS Trajectory Data Analysis of the saMurE–Compound 2 Complex
2.4. Analysis of Binding Modes and Binding Free Energies of saMurE and Compound 2
2.5. Growth Inhibition Assay for Gram-Negative Bacterium
2.6. Prediction of Pharmacological Properties and Toxicity of Compound 2
2.7. Toxicity Assays for Mammalian-Derived Cells
2.8. Membrane Permeation Simulation of Compound 2 against Gram-Positive Bacteria
2.9. Interaction Analysis of Compound 2 and Other Members of the Mur ligase Family by MDSs
2.10. MDS Trajectory Analysis of Compound 2 and MurC, MurD, and MurF Complexes
3. Discussion
3.1. In Silico SBDS Constructed by Hierarchical Combination of DS and MS
3.2. Antimicrobial Spectrum of Compound 2
3.3. Potential Multiple Pharmacological Properties of Compound 2
3.4. In Silico Toxicity Prediction and In Vitro Cytotoxicity Assay Using Mammalian-Derived Cells
3.5. Major Group of Amino Acid Residues That Support Stable Binding of Compound 2
3.6. Diversity of Compound 2 Targets
4. Materials and Methods
4.1. Compound Structure Data Library
4.2. Pretreatment of Target Proteins
4.3. Docking Simulation
4.4. Molecular Dynamics Simulation
4.5. MDS Trajectory Data Analysis
4.6. Umbrella Sampling
4.7. Preparation of Compounds
4.8. Bacterial Growth Inhibition Assay
4.9. Toxicity Assays for Mammalian-Derived Cells
4.10. Ab Initio Fragment Molecular Orbital (FMO) Calculation
4.11. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Teshima, M.; Monobe, K.; Okubo, S.; Aoki, S. Discovery of Antibacterial Compounds with Potential Multi-Pharmacology against Staphylococcus Mur ligase Family Members by In Silico Structure-Based Drug Screening. Molecules 2024, 29, 3792. https://doi.org/10.3390/molecules29163792
Teshima M, Monobe K, Okubo S, Aoki S. Discovery of Antibacterial Compounds with Potential Multi-Pharmacology against Staphylococcus Mur ligase Family Members by In Silico Structure-Based Drug Screening. Molecules. 2024; 29(16):3792. https://doi.org/10.3390/molecules29163792
Chicago/Turabian StyleTeshima, Mio, Kohei Monobe, Saya Okubo, and Shunsuke Aoki. 2024. "Discovery of Antibacterial Compounds with Potential Multi-Pharmacology against Staphylococcus Mur ligase Family Members by In Silico Structure-Based Drug Screening" Molecules 29, no. 16: 3792. https://doi.org/10.3390/molecules29163792
APA StyleTeshima, M., Monobe, K., Okubo, S., & Aoki, S. (2024). Discovery of Antibacterial Compounds with Potential Multi-Pharmacology against Staphylococcus Mur ligase Family Members by In Silico Structure-Based Drug Screening. Molecules, 29(16), 3792. https://doi.org/10.3390/molecules29163792