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<p>Antimicrobial resistance is a major public health concern with significant future implications. Among potential alternatives for pathogen inhibition, antimicrobial peptides (AMPs), particularly pediocin-like bacteriocins, are noteworthy due to their efficacy and reduced toxicity to hosts and the environment. In this context, peptide repurposing is relevant for the development of strategies against <i>Candida albicans</i>, an opportunistic pathogen associated with high mortality and healthcare costs. This study evaluated in silico the interactions between four pediocin-like bacteriocins (Coagulin A, Pediocin PA-1, Penocin A, and Plantaricin 423) and the secreted aspartic protease 2 (SAP2) of <i>C. albicans</i>, a validated antifungal target. Through structural modeling, we have generated high-quality models with conserved structural features. Then, molecular docking and MM/GBSA analyses identified Coagulin A and Pediocin PA-1 as the peptides with the most favorable binding energies and energetically coherent interactions with the SAP2 catalytic dyad, with electrostatic and van der Waals interactions predominating across all complexes, respectively. Molecular dynamics analyses, including RMSD, RMSF, Radius of gyration, Solvent-accessible surface area and Binding energy, demonstrated that Coagulin A and Pediocin PA-1 as the peptides with the most favorable binding energies and coherent interactions with the active site residues of SAP2, specifically the catalytic dyad ASP32 and ASP218, stabilizing in low-flexibility conformations, whereas Penocin A induced more solvated and structurally expanded states, and Plantaricin 423 showed intermediate behavior. These findings highlight the potential of Coagulin A and Pediocin PA-1 as SAP2 inhibitors and provide a computational foundation for developing novel antifungal strategies against <i>C. albican</i>s.</p>

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Multistep molecular assessment of pediocin-like bacteriocins as antifungal agents targeting secreted aspartic protease 2 (SAP2) of Candida albicans through computational modeling and molecular dynamics

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月26日

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  • Iago Rodrigues Blanco,
  • Ricardo Pinheiro de Souza Oliveira,
  • Matheus M. Pereira

摘要

Antimicrobial resistance is a major public health concern with significant future implications. Among potential alternatives for pathogen inhibition, antimicrobial peptides (AMPs), particularly pediocin-like bacteriocins, are noteworthy due to their efficacy and reduced toxicity to hosts and the environment. In this context, peptide repurposing is relevant for the development of strategies against Candida albicans, an opportunistic pathogen associated with high mortality and healthcare costs. This study evaluated in silico the interactions between four pediocin-like bacteriocins (Coagulin A, Pediocin PA-1, Penocin A, and Plantaricin 423) and the secreted aspartic protease 2 (SAP2) of C. albicans, a validated antifungal target. Through structural modeling, we have generated high-quality models with conserved structural features. Then, molecular docking and MM/GBSA analyses identified Coagulin A and Pediocin PA-1 as the peptides with the most favorable binding energies and energetically coherent interactions with the SAP2 catalytic dyad, with electrostatic and van der Waals interactions predominating across all complexes, respectively. Molecular dynamics analyses, including RMSD, RMSF, Radius of gyration, Solvent-accessible surface area and Binding energy, demonstrated that Coagulin A and Pediocin PA-1 as the peptides with the most favorable binding energies and coherent interactions with the active site residues of SAP2, specifically the catalytic dyad ASP32 and ASP218, stabilizing in low-flexibility conformations, whereas Penocin A induced more solvated and structurally expanded states, and Plantaricin 423 showed intermediate behavior. These findings highlight the potential of Coagulin A and Pediocin PA-1 as SAP2 inhibitors and provide a computational foundation for developing novel antifungal strategies against C. albicans.