Molecular docking, molecular dynamics simulation and MM-PB/GBSA analysis for the inhibition of Klebsiella pneumoniae SHV-1 β-lactamase using antimicrobial peptides defensin VvK1 and snakin-1
This computational study aims to explore the inhibition property of two plant-derived AMPs (antimicrobial peptides), defensin VvK1 and snakin-1, against SHV-1 β-lactamase from Klebsiella pneumoniae by molecular docking, MDS (molecular dynamics simulation) and MM-PB/GBSA (Molecular Mechanics-Poisson-...
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| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
KeAi Communications Co., Ltd.
2025-06-01
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| Series: | Biomedical Analysis |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950435X25000320 |
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| Summary: | This computational study aims to explore the inhibition property of two plant-derived AMPs (antimicrobial peptides), defensin VvK1 and snakin-1, against SHV-1 β-lactamase from Klebsiella pneumoniae by molecular docking, MDS (molecular dynamics simulation) and MM-PB/GBSA (Molecular Mechanics-Poisson-Boltzmann/Generalized Born Surface Area) analysis. The AMPs (defensin VvK1 and snakin-1) were docked to SHV-1 β-lactamase for intermolecular (protein-peptide) interaction analysis and binding affinity prediction. SHV-1-defensin-VvK1 and SHV-1-snakin-1 complexes were subjected to MM-PB/GBSA free binding energy calculations after 10 ns MDS. To compare the efficacy of stronger AMP, defensin-VvK1, with reference inhibitor, cymal-6, 50 ns MDS was accomplished. Safety profiles of the AMPs were predicted by allergenicity and toxicity testing. Docking study revealed lower binding free energy for top-ranked SHV-1-snakin-1 complex than SHV-1-defensin-VvK1. SHV-1-defensin-VvK1 was energetically stronger than SHV-1-snakin-1 at 10 ns MDS run. After 50 ns MDS run, defensin-VvK1 (MM-PBSA: −70.73 ± 0.57 kcal/mol; MM-GBSA: −62.53 ± 0.43 kcal/mol) showed stronger efficacy than cymal-6 (MM-PBSA: −21.46 ± 0.50 kcal/mol; MM-GBSA: −26.79 ± 0.34 kcal/mol) against SHV-1. Both the AMPs demonstrated acceptable physicochemical properties, and were found non-allergenic and non-toxic. Thus, current in silico study validated the anti-Klebsiella pneumoniae activity of naturally occurring AMPs (snakin-1 and defensin-VvK1), wherein defensin-VvK1 showed higher activity against SHV-1 β-lactamase. Therefore, the AMPs currently being studied could be used as alternative biotherapeutic agents to combat life-threatening infections caused by antibiotic resistant bacterial pathogens. Overall, the findings can be translated into the process of designing and developing peptide-based therapeutics by targeting bacterial β-lactamases. |
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| ISSN: | 2950-435X |