In Silico Study of the Early Stages of Aggregation of β-Sheet Forming Antimicrobial Peptide GL13K

Antimicrobial peptides (AMPs) are of growing interest as potential candidates for antibiotics to which antimicrobial resistance increases slowly. In this article, we perform the first in silico study of the synthetic {beta} sheet-forming AMP GL13K. Through atomistic simulations of single and multipeptide systems under different charge conditions, we are able to shine a light on the short timescales of early aggregation. We find that isolated peptide conformations are primarily dictated by sequence rather than charge, whereas changing charge has a significant impact on the conformational free energy landscape of multi-peptide systems. We demonstrate that the lack of charge-charge repulsion is a sufficient minimal model for experimentally observed aggregation. Overall, our work explores the molecular biophysical underpinnings of the first stages of aggregation of a unique AMP, laying necessary groundwork for its further development as an antibiotic candidate.