文献类型：期刊文献

英文题名：Activity of Antimicrobial Peptide Aggregates Decreases with Increased Cell Membrane Embedding Free Energy Cost

作者：Zou, Rongfeng[1,2,3];Zhu, Xiaomin[1,2];Tu, Yaoquan[3];Wu, Junchen[1,2,4];Landry, Markita P.[4,5,6]

机构：[1]East China Univ Sci & Technol, Sch Chem & Mol Engn, Key Lab Adv Mat, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Chem & Mol Engn, Inst Fine Chem, Shanghai 200237, Peoples R China;[3]KTH Royal Inst Technol, Div Theoret Chem & Biol, Sch Biotechnol, SE-10691 Stockholm, Sweden;[4]Univ Calif Berkeley, Dept Chem & Biomol Engn, 476 Stanley Hall, Berkeley, CA 94720 USA;[5]Chan Zuckerberg Biohub, San Francisco, CA USA;[6]Univ Calif Berkeley, Calif Inst Quantitat Biosci Qb3, Berkeley, CA 94720 USA

年份：2018

卷号：57

期号：18

起止页码：2606

外文期刊名：BIOCHEMISTRY

收录：;EI(收录号：20182005198068);WOS:【SCI-EXPANDED(收录号:WOS:000431927100008)】；

基金：This work was supported by a Burroughs Welcome Fund Career Award at the Scientific Interface (CASI), the Foundation for Food and Agricultural Research (FFAR), and a Beckman Foundation Young Investigator Award (M.P.L.). M.P.L. is a Chan-Zuckerberg Biohub Investigator. We thank the NSFC (91529101, 21572057, and 21778017) for financial support. R.Z. thanks the China Scholarship Council for financial support. We also thank the Swedish National Infrastructure for Computing (SNIC) for providing computational resources for Project SNIC 2016-1-343 and SNIC2016-34-43.

语种：英文

外文关键词：Bioactivity - Gibbs free energy - Antibiotics - Cytology - Hydrogen bonds - Molecular dynamics - Bacteria - Free energy

摘要：Antimicrobial peptides (AMPs) are a promising alternative to antibiotics for mitigating bacterial infections, in light of increasing bacterial resistance to antibiotics. However, predicting, understanding, and controlling the antibacterial activity of AMPs remain a significant challenge. While peptide intramolecular interactions are known to modulate AMP antimicrobial activity, peptide intermolecular interactions remain elusive in their impact on peptide bioactivity. Herein, we test the relationship between AMP intermolecular interactions and antibacterial efficacy by controlling AMP intermolecular hydrophobic and hydrogen bonding interactions. Molecular dynamics simulations and Gibbs free energy calculations in concert with experimental assays show that increasing intermolecular interactions via interpeptide aggregation increases the energy cost for the peptide to embed into the bacterial cell membrane, which in turn decreases the AMP antibacterial activity. Our findings provide a route for predicting and controlling the antibacterial activity of AMPs against Gram-negative bacteria via reductions of intermolecular AMP interactions.