H, SK, Jade, D, Harrison, MA orcid.org/0000-0002-7826-7472 et al. (1 more author) (2022) Identification of natural inhibitor against L1 β-lactamase present in Stenotrophomonas maltophilia. Journal of Molecular Modeling, 28. 342. ISSN 1610-2940
Abstract
Antibiotic resistance is threatening the medical industry in treating microbial infections. Many organisms are acquiring antibiotic resistance because of the continuous use of the same drug. Gram-negative organisms are developing multi-drug resistance properties (MDR) due to chromosomal level changes that occurred as a part of evolution or some intrinsic factors already present in the organism. Stenotrophomonas maltophilia falls under the category of multidrug-resistant organism. WHO has also urged to evaluate the scenario and develop new strategies for making this organism susceptible to otherwise resistant antibiotics. Using novel compounds as drugs can ameliorate the issue to some extent. The β-lactamase enzyme in the bacteria is responsible for inhibiting several drugs currently being used for treatment. This enzyme can be targeted to find an inhibitor that can inhibit the enzyme activity and make the organism susceptible to β-lactam antibiotics. Plants produce several secondary metabolites for their survival in adverse environments. Several phytoconstituents have antimicrobial properties and have been used in traditional medicine for a long time. The computational technologies can be exploited to find the best compound from many compounds. Virtual screening, molecular docking, and dynamic simulation methods are followed to get the best inhibitor for L1 β-lactamase. IMPPAT database is screened, and the top hit compounds are studied for ADMET properties. Finally, four compounds are selected to set for molecular dynamics simulation. After all the computational calculations, withanolide R is found to have a better binding and forms a stable complex with the protein. This compound can act as a potent natural inhibitor for L1 β-lactamase.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022. This is an author produced version of an article published in Journal of Molecular Modeling. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Docking; L1 β-lactamase; Molecular dynamics; Virtual screening |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 04 Nov 2022 11:55 |
Last Modified: | 05 Oct 2023 00:13 |
Status: | Published |
Publisher: | Springer |
Identification Number: | 10.1007/s00894-022-05336-z |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:192539 |