In silico and in vitro studies on membrane acting small antimicrobial agents

Abstract

Antimicrobial resistance (AMR) poses a pressing global healthcare challenge, demanding innovative strategies to counter the rise of multidrug-resistant pathogens. This investigation utilizes both molecular dynamics (MD) simulations and experimental validation to delve into the membrane-penetrating behavior and pore-forming activity of recently developed small antimicrobial peptides (AMPs). The increasing prevalence of AMR, attributed to antibiotic misuse and horizontal gene transfer, has given rise to formidable infections, especially during critical medical procedures. Conventional antibiotics now face resistance, prompting a shift towards exploring alternative strategies, including antimicrobial peptides found in various organisms. This study evaluates the potential of compounds 5, 6, 7, and 8 as antimicrobial peptides (AMPs) using molecular dynamics (MD) simulations. MD simulations predicted stable pore formation in the bacterial membrane for compounds 5 and 6, while compounds 7 and 8 exhibited unexpected anchoring behavior. Experimental assays corroborated the simulation results, highlighting the importance of experimental validation in AMP design. The observed discrepancies between intended and observed behavior emphasize the complexity of AMP interactions and advocate for a holistic approach. The successful validation underscores the potential of MD simulations for AMP development. Future research avenues include exploring higher oligomeric structures and refining AMP design for improved efficacy. newline