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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KeAi Communications Co., Ltd.
2025-06-01
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| Series: | Biomedical Analysis |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950435X25000320 |
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| author | Manisha Mandal Shyamapada Mandal |
| author_facet | Manisha Mandal Shyamapada Mandal |
| author_sort | Manisha Mandal |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3998eb7a2ccd4d01afbe939440b908df |
| institution | OA Journals |
| issn | 2950-435X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | KeAi Communications Co., Ltd. |
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| series | Biomedical Analysis |
| spelling | doaj-art-3998eb7a2ccd4d01afbe939440b908df2025-08-20T02:37:33ZengKeAi Communications Co., Ltd.Biomedical Analysis2950-435X2025-06-0122395010.1016/j.bioana.2025.06.001Molecular 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-1Manisha Mandal0Shyamapada Mandal1Department of Physiology, MGM Medical College, Kishanganj, Bihar 855107, IndiaDepartment of Zoology, University of Gour Banga, West Bengal, Malda 732103, India; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2950435X25000320SHV-1 β-lactamaseKlebsiella pneumoniaeAntimicrobial peptidesMolecular dockingMM-PB/GBSA binding free energy |
| spellingShingle | Manisha Mandal Shyamapada Mandal 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 Biomedical Analysis SHV-1 β-lactamase Klebsiella pneumoniae Antimicrobial peptides Molecular docking MM-PB/GBSA binding free energy |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | SHV-1 β-lactamase Klebsiella pneumoniae Antimicrobial peptides Molecular docking MM-PB/GBSA binding free energy |
| url | http://www.sciencedirect.com/science/article/pii/S2950435X25000320 |
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