In Silico Determination, Engineering Demonstration, and Preliminary Docking Studies of Potential Antimicrobial Peptides from Cocosin-1 against Methicillin-Resistant Staphylococcus aureus (MRSA) Muramyl E (MurE) Ligase

Authors

E. Dario Driyah Nicole, De La Salle Medical and Health Sciences Institute
Kuven A. Malig-on, De La Salle Medical and Health Sciences Institute
Anna Fatima M. Perea, De La Salle Medical and Health Sciences Institute
Nedrick T. Distor, College of Natural Sciences and Mathematics

Publication Date

9-1-2025

Document Type

Article

Publication Title

Biochemistry Moscow Supplement Series B Biomedical Chemistry

Abstract

Abstract: The alarming rise of antibiotic resistance triggered the search for antimicrobial alternatives such as plant-based antimicrobial peptides (AMPs) since they possess a wide range of bioactivities. Herein, we evaluated the antimicrobial probability of peptides from enzyme-digested cocosin-1, improved the antimicrobial probability of selected peptides through engineering, and investigated possible peptide-enzyme interactions. Cocosin-1 was individually digested using pepsin, trypsin, and chymotrypsin, generating AMPs which were analyzed for their antimicrobial probabilities. This approach yielded 9 (CAMPR3) and 25 AMPs (Deep-AmPEP30). The top three peptides with the highest antimicrobial probabilities produced per enzyme were subjected to site-specific amino acid (histidine) substitution while maintaining the conserved sequences intact. The physicochemical properties of the top five engineered peptides were assessed to evaluate their potential efficacy. To understand their mechanisms of action, the original and engineered AMPs with the highest antimicrobial probabilities were modeled and docked against methicillin-resistant Staphylococcus aureus (MRSA) MurE ligase, a bacterial enzyme critical for cell wall biosynthesis. Upon histidine substitution, peptide C1DP-C1 (¹²⁹QRSEREEGERHRW¹⁴¹) displayed the highest antimicrobial probability (82.45%) while peptide CIDP-P2 (³³QSPRRSVSSRNECRIERL⁵⁰) showed the most significant antimicrobial probability improvement (31.70%). Docking studies revealed essential binding interactions, including salt bridges and hydrogen bonding, which may be crucial in AMP-based enzyme inhibition. Overall, this study provides a foundational idea that site-specific changes in the amino acid composition may affect and improve the antimicrobial activity of selected peptides for potential antibacterial therapeutics.

First Page

244

Last Page

257

APA Citation

Dario, Driyah & Malig-on, Kuven & Perea, Anna & Distor, Nedrick. (2025). In Silico Determination, Engineering Demonstration, and Preliminary Docking Studies of Potential Antimicrobial Peptides from Cocosin-1 against Methicillin-Resistant Staphylococcus aureus (MRSA) Muramyl E (MurE) Ligase. Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry. 19. 244-257. 10.1134/S1990750825600499.