Antimicrobial peptides (AMPs) are of growing interest as potential candidates that may offer more resilience against antimicrobial resistance than traditional antibiotic agents. In this article, we perform the first in silico study of the synthetic ß sheet‐forming AMP GL13K. Through atomistic simulations of single and multi‐peptide systems under different 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 loss 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.

中文翻译：

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β片形成抗菌肽 GL13K 聚集早期阶段的计算机模拟研究

抗菌肽（AMP）作为潜在的候选者越来越受到人们的关注，因为它可能比传统的抗生素药物更能抵抗抗菌素耐药性。在本文中，我们对合成的 β 片层形成 AMP GL13K 进行了首次计算机研究。通过在不同条件下对单肽和多肽系统进行原子模拟，我们能够揭示早期聚集的短时间尺度。我们发现分离的肽构象主要由序列而不是电荷决定，而改变电荷对多肽系统的构象自由能景观具有重大影响。我们证明，电荷-电荷排斥的损失对于实验观察到的聚集来说是一个足够的最小模型。总体而言，我们的工作探索了独特 AMP 聚合第一阶段的分子生物物理基础，为其进一步开发作为候选抗生素奠定了必要的基础。