Identifying potential inhibitors of biofilm-antagonistic proteins to promote biofilm formation: a virtual screening and molecular dynamics simulations approach.
Biofilm-antagonistic proteins
Biofilms
In silico
Molecular docking
Molecular dynamics
Virtual screening
Journal
Molecular diversity
ISSN: 1573-501X
Titre abrégé: Mol Divers
Pays: Netherlands
ID NLM: 9516534
Informations de publication
Date de publication:
Aug 2022
Aug 2022
Historique:
received:
25
06
2021
accepted:
14
09
2021
pubmed:
22
9
2021
medline:
3
8
2022
entrez:
21
9
2021
Statut:
ppublish
Résumé
Microbial biofilms play a critical role in environmental biotechnology and associated applications. Biofilm production can be enhanced by inhibiting the function of proteins that negatively regulate their formation. With this objective, an in silico approach was adopted to identify competitive inhibitors of eight biofilm-antagonistic proteins, namely AbrB and SinR (from Bacillus subtilis) and AmrZ, PDE (EAL), PslG, RetS, ShrA and TpbA (from Pseudomonas aeruginosa). Fifteen inhibitors that structurally resembled the natural ligand of each protein were shortlisted using ligand-based and structure-based virtual screening. The top four inhibitors obtained from molecular docking using Autodock Vina were further docked using SwissDock and DOCK 6.9 to obtain a consensus hit for each protein based on different scoring functions. Further analysis of the protein-ligand complexes revealed that these top inhibitors formed significant non-covalent interactions with their respective protein binding sites. The eight protein-ligand complexes were then subjected to molecular dynamics simulations for 30 ns using GROMACS. RMSD and radius of gyration values of 0.1-0.4 nm and 1.0-3.5 nm, respectively, along with hydrogen bond formation throughout the trajectory indicated that all the complexes remained stable, compact and intact during the simulation period. Binding energy values between -20 and -77 kJ/mol obtained from MM-PBSA calculations further confirmed the high affinities of the eight inhibitors for their respective receptors. The outcome of this study holds great promise to enhance biofilms that are central to biotechnological processes associated with microbial electrochemical technologies, wastewater treatment, bioremediation and the industrial production of value-added products.
Identifiants
pubmed: 34546549
doi: 10.1007/s11030-021-10320-5
pii: 10.1007/s11030-021-10320-5
doi:
Substances chimiques
Ligands
0
Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2135-2147Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
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