دورية أكاديمية
Free Energy Analysis of Peptide-Induced Pore Formation in Lipid Membranes by Bridging Atomistic and Coarse-Grained Simulations.
| العنوان: | Free Energy Analysis of Peptide-Induced Pore Formation in Lipid Membranes by Bridging Atomistic and Coarse-Grained Simulations. |
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| المؤلفون: | Richardson JD; Department of Chemical and Biological Engineering, University of Wisconsin─Madison, Madison, Wisconsin 53706, United States., Van Lehn RC; Department of Chemical and Biological Engineering, University of Wisconsin─Madison, Madison, Wisconsin 53706, United States.; Department of Chemistry, University of Wisconsin─Madison, Madison, Wisconsin 53706, United States. |
| المصدر: | The journal of physical chemistry. B [J Phys Chem B] 2024 Sep 12; Vol. 128 (36), pp. 8737-8752. Date of Electronic Publication: 2024 Aug 29. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 101157530 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-5207 (Electronic) Linking ISSN: 15205207 NLM ISO Abbreviation: J Phys Chem B Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, D.C. : American Chemical Society, c1997- |
| مواضيع طبية MeSH: | Molecular Dynamics Simulation* , Antimicrobial Cationic Peptides*/chemistry , Antimicrobial Cationic Peptides*/pharmacology , Thermodynamics* , Lipid Bilayers*/chemistry , Lipid Bilayers*/metabolism , Melitten*/chemistry , Melitten*/metabolism , Magainins*/chemistry , Magainins*/pharmacology |
| مستخلص: | Antimicrobial peptides (AMPs) are attractive materials for combating the antimicrobial resistance crisis because they can kill target microbes by directly disrupting cell membranes. Although thousands of AMPs have been discovered, their molecular mechanisms of action are still poorly understood. One broad mechanism for membrane disruption is the formation of membrane-spanning hydrophilic pores which can be stabilized by AMPs. In this study, we use molecular dynamics simulations to investigate the thermodynamics of pore formation in model single-component lipid membranes in the presence of one of three AMPs: aurein 1.2, melittin and magainin 2. To overcome the general challenge of modeling long time scale membrane-related behaviors, including AMP binding, clustering, and pore formation, we develop a generalizable methodology for sampling AMP-induced pore formation. This approach involves the long equilibration of peptides around a pore created with a nucleation collective variable by performing coarse-grained simulations, then backmapping equilibrated AMP-membrane configurations to all-atom resolution. We then perform all-atom simulations to resolve free energy profiles for pore formation while accurately modeling the interplay of lipid-peptide-solvent interactions that dictate pore formation free energies. Using this approach, we quantify free energy barriers for pore formation without direct biases on peptides or whole lipids, allowing us to investigate mechanisms of pore formation for these 3 AMPs that are a consequence of unbiased peptide diffusion and clustering. Further analysis of simulation trajectories then relates variations in pore lining by AMPs, AMP-induced lipid disruptions, and salt bridges between AMPs to the observed pore formation free energies and corresponding mechanisms. This methodology and mechanistic analysis have the potential to generalize beyond the AMPs in this study to improve our understanding of pore formation by AMPs and related antimicrobial materials. |
| المشرفين على المادة: | 0 (Antimicrobial Cationic Peptides) 0 (Lipid Bilayers) 20449-79-0 (Melitten) 0 (Magainins) 0 (aurein 1.2 peptide) |
| تواريخ الأحداث: | Date Created: 20240829 Date Completed: 20240912 Latest Revision: 20240912 |
| رمز التحديث: | 20240912 |
| DOI: | 10.1021/acs.jpcb.4c03276 |
| PMID: | 39207202 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 1520-5207 |
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| DOI: | 10.1021/acs.jpcb.4c03276 |