On the Aggregation State of Synergistic Antimicrobial Peptides
Jacob M. Remington, Chenyi Liao, Mona Sharafi, Emma Ste. Marie,, Jonathon B. Ferrell, Robert Hondal, Matthew J. Wargo, Severin T. Schneebeli,, and Jianing Li

TL;DR
This study investigates how the aggregation of antimicrobial peptides influences their synergistic activity, providing new insights into their molecular interactions and guiding future therapeutic development.
Contribution
It reveals the role of peptide co-aggregation in AMP synergy through combined simulation and experimental approaches, a novel insight in the field.
Findings
Peptide co-aggregation occurs at optimal concentrations and ratios.
Aggregation affects membrane disruption by AMPs.
Provides molecular-level understanding of AMP synergy.
Abstract
By integrating various simulation and experimental techniques, we discovered that antimicrobial peptides (AMPs) may achieve synergy at an optimal concentration and ratio, which can be caused by aggregation of the synergistic peptides. On multiple time and length scales, our studies obtain novel evidence of how peptide co-aggregation in solution can affect disruption of membranes by synergistic AMPs. Our findings provide crucial details about the complex molecular origins of AMP synergy, which will help guide the future development of synergistic AMPs as well as applications of anti-infective peptide cocktail therapies.
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Taxonomy
TopicsAntimicrobial Peptides and Activities · Biochemical and Structural Characterization · Protein Structure and Dynamics
