Antimicrobial Peptide Design, Molecular Docking and ADMET Studies Against the Methicillin-Resistant Staphylococcus aureus and Carbapenem resistant and Carbapenemase-producing Pseudomonas aeruginosa
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Date
2022-10
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Trends in Peptide and Peptide Sciences
Abstract
Carbapenem-resistant and carbapenemase-producing Pseudomonas aeruginosa (CRPA)
and methicillin-resistant Staphylococcus aureus (MRSA) are two pathogens that are
resistant to currently available antimicrobials. As an alternative to effective medication
molecules, antimicrobial peptides (AMPs) have the potential to cure superbug-caused
infections effectively. Two new AMPs (ama1 and ama2) were designed utilizing a
knowledge-based technique with optimal parameters. First, the PEP-FOLD 3.5 server
made a de novo prediction of the AMPs' three-dimensional (3D) structure, which was
validated using PROCHECK of SAVES v6.0 by checking the amino acid locations in the
Ramachandra plot. Then, protein-peptide docking simulations of the predicted AMPs and
reference AMP (Aurein 1.2) for positive control were performed using the HPEPDOCK
docking web server, followed by the computation of the AMPs' physicochemical
parameters and toxicity profile using the ProtParam and vNN-ADMET web servers,
respectively. The sequences for ama1 and ama2 were AWGKIKALR and IKWLRLAKP,
respectively. Docking analysis revealed that the antibacterial activity of ama1 and ama2
was superior to that of Aurein 1.2 against CRPA-resistant enzyme (6ew3), respectively.
However, ama1, ama2, and Aurein 1.2 inhibited the activity of MRSA-resistant protein
(4c12). Both the physicochemical qualities and the toxicity profiles were advantageous.
Therefore, the in-silico-derived AMPs could serve as a pharmaceutical candidate for
developing multidrug-resistant bacteria-effective antimicrobials.
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Keywords
Antimicrobial peptides, Molecular docking Pseudomonas aeruginosa Pharmacokinetic parameters Resistant pathogens Staphylococcus aureus