Ensemble-based, high-throughput virtual screening of potential inhibitor targeting putative farnesol dehydrogenase of Metisa plana (Lepidoptera: Psychidae)

Metisa plana (Lepidoptera: Psychidae) bagworm is a leaf-eater caterpillar ubiquitously found as a damaging pest in oil palm plantations, specifically in Malaysia. Various strategies have been implemented, including the usage of chemical insecticides. However, the main challenges include the developm...

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Published in:Computational biology and chemistry 2023-04, Vol.103, p.107811-107811, Article 107811
Main Authors: Zifruddin, Anis Nadyra, Mohamad Yusoff, Mohamad Ariff, Abd Ghani, Nur Syatila, Nor Muhammad, Nor Azlan, Lam, Kok Wai, Hassan, Maizom
Format: Article
Language:English
Subjects:
Animals
Farnesol dehydrogenase
High-throughput virtual screening
Insecta
Insecticides
Juvenile Hormones
Lepidoptera
Metisa plana
Molecular docking
Molecular Docking Simulation
Molecular Dynamics Simulation
Protein structure prediction
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Summary:Metisa plana (Lepidoptera: Psychidae) bagworm is a leaf-eater caterpillar ubiquitously found as a damaging pest in oil palm plantations, specifically in Malaysia. Various strategies have been implemented, including the usage of chemical insecticides. However, the main challenges include the development of insecticide resistance and its detrimental effects on the environment and non-target organisms. Therefore, a biorational insecticide is introduced by targeting the juvenile hormone (JH) biosynthetic pathway, which is mainly present in the insect and vital for the insect's growth, diapause, metamorphosis, and adult reproduction. This study aimed to investigate the potential inhibitor for the rate-limiting enzyme involved in the JH pathway known as farnesol dehydrogenase. A 255 amino acids sequence encoded for the putative M. plana farnesol dehydrogenase (MpFolDH) open reading frame had been identified and isolated. The three-dimensional structure of MpFolDH was predicted to have seven β- sheets with α-helices at both sides, showing typical characteristics for classical short-chain dehydrogenase and associated with oxidoreductase activity. Then, the ensemble-based virtual screening was conducted based on the ZINC20 database, in which 43 768 compounds that fulfilled pesticide-likeness criteria were screened by site-specific molecular docking. After a short molecular dynamics simulation (5 ns) was conducted towards 102 compounds, only the top 10 compounds based on their most favourable binding energy were selected for a more extended simulation (100 ns). Based on the protein-ligand stability, protein compactness, residues rigidity, binding interaction, binding energy throughout the 100 ns simulation, and physicochemical analysis, ZINC000408743205 was selected as a potential inhibitor for this enzyme. Amino acids decomposition analysis indicates Ile18, Ala95, Val198 and Val202 were the critical contributor residues for MpFolDH-inhibitors(s) complex. [Display omitted] •MpFoLDH was predicted as typical classical short-chain dehydrogenase.•A total of 43 768 compounds were docked to the three different protein conformations.•A final 10 compounds were subjected to molecular dynamics simulation for 100 ns.•ZINC000408743205 was selected as the most potential inhibitor for MpFolDH.•Ile18, Ala95, Val198 and Val202 were the key main residues for the complex.
ISSN:1476-9271
1476-928X
DOI:10.1016/j.compbiolchem.2023.107811