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PreprintCited by 4Computational Drug Discovery MethodsVector-borne infectious diseasesvaccines and immunoinformatics approaches

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Exploring Novel Inhibitors for Babesia bigemina Lactate Dehydrogenase: A Computational Structural Biology Perspective

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Bostancioglu, Safiye Merve, Mutlu, Ozal·2024·Parasitology Research
DOI 10.21203/rs.3.rs-4951492/v1

Preprint — published as 10.1007/s00436-024-08433-5 · Paper page

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Abstract

Babesia bigemina is an apicomplexan parasite and causes “Texas fever” in bovines. Lactate dehydrogenase (LDH) is an essential enzyme in regulating anaerobic metabolism. The presence of five amino acid insertion in the active site of many apicomplexan LDH makes a significant difference between the parasitic LDH and the host counterpart. Therefore, apicomplexan LDH is an attractive drug target. In this study, a structure-based drug discovery approach was performed to find novel inhibitor candidates. In the first round, possible candidates were identified by following the virtual screening workflow. Then, the compounds with favourable docking scores were filtered using the QM-polarized ligand docking and induced fit docking methods. As a result, 20 novel compounds that bind to the active site of the BbigLDH and have low affinity with the host LDHs have been identified. Molecular dynamics simulations of the complexes (in total 8.8 µs) were performed and binding free energies were calculated. In conclusion, compounds named C09, C16 and C18 deserve further investigation to better understand their potential therapeutic effects on babesiosis. The findings of this study, elucidating the structural properties of BbigLDH enzyme and discovering its potential inhibitors, might pave the way for further research in developing LDH-targeted therapeutic interventions.

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Metadata

Authors
Bostancioglu, S. M., & Mutlu, O.
Affiliations
  • Marmara University (TR)
  • Marmara University
ORCID
Bostancioglu, Safiye Merve
Venue
Parasitology Research
Publisher
Springer Science and Business Media LLC
Published
2024-09-24
Volume
124
Issue
1
Pages
1-1
ISSN
0044-3255 (ISSN-L)
DOI
10.21203/rs.3.rs-4951492/v1
OpenAlex
W4406115356
Cited by
4
References
1
Citations by year
2026: 1 · 2025: 3
FWCI
2.08
Type
journal article
Language
en
Open access
Licence
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations
  • Parasitology Research (publishedVersion)
  • Research Square (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Marmara Üniversitesi (FDK-2022-10061)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Computational Drug Discovery Methods
  • Life Sciences › Immunology and Microbiology › Parasitology › Vector-borne infectious diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
Keywords
Babesia bigemina, lactate dehydrogenase, bovine babesiosis, Texas fever, structure-based drug design, virtual screening, induced fit docking, binding free energy, molecular dynamics simulation, enzyme inhibitors, Apicomplexa
MeSH terms
Animals, Antiprotozoal Agents, Babesia, Babesiosis, Cattle, Enzyme Inhibitors, L-Lactate Dehydrogenase, Computational Biology, Catalytic Domain, Drug Discovery, Molecular Dynamics Simulation, Molecular Docking Simulation

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