2016
DOI: 10.1038/ncomms13535
|View full text |Cite
|
Sign up to set email alerts
|

Abstract: Many antimicrobial peptides (AMPs) selectively target and form pores in microbial membranes. However, the mechanisms of membrane targeting, pore formation and function remain elusive. Here we report an experimentally guided unbiased simulation methodology that yields the mechanism of spontaneous pore assembly for the AMP maculatin at atomic resolution. Rather than a single pore, maculatin forms an ensemble of structurally diverse temporarily functional low-oligomeric pores, which mimic integral membrane protei… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1
1

Citation Types

5
126
0

Year Published

2017
2017
2023
2023

Publication Types

Select...
10

Relationship

4
6

Authors

Journals

citations
Cited by 91 publications
(131 citation statements)
references
References 39 publications
5
126
0
Order By: Relevance
“…The cumulative sampling in this study amounts to 32 ms for the simulations presented in the main text (16 ms of free simulations and 16 ms of HREX), and 72 ms for the additional simulations reported in the Supporting Material (8 ms of HREX, 4 ms of metadynamics, and 60 ms of umbrella sampling). These are state-of-the-art timescales, approaching those in contemporary supercomputer studies of other authors like, e.g., that in Wang et al (65).…”
Section: Force Fields General Simulation Parameters and Starting Stmentioning
confidence: 64%
“…The cumulative sampling in this study amounts to 32 ms for the simulations presented in the main text (16 ms of free simulations and 16 ms of HREX), and 72 ms for the additional simulations reported in the Supporting Material (8 ms of HREX, 4 ms of metadynamics, and 60 ms of umbrella sampling). These are state-of-the-art timescales, approaching those in contemporary supercomputer studies of other authors like, e.g., that in Wang et al (65).…”
Section: Force Fields General Simulation Parameters and Starting Stmentioning
confidence: 64%
“…These peptides bind to cell membranes and spontaneously assemble in the lipid bilayer as a channel or pore-like structure, though not all are cytolytic ( Figure 5). Well-known natural examples are gramicidin [68], colistin [67], melittin [69,70], maculatin [71], and alamethicin [72]. The two common models for the channel structures are barrel-stave and toroidal, depending on how the peptide interacts with the lipid headgroups [73].…”
Section: Membrane-active Peptides (Maps)mentioning
confidence: 99%
“…It is likely that the detailed pore-forming mechanism varies between different AMPs. A number of computational studies have attempted to address possible mechanisms of pore formation and/or interaction with membranes (5)(6)(7)(8)(9)(10)(11)(12)(13). Such studies can reveal aspects of the underlying mode(s) of action of AMPs and thereby provide a guide for design of novel antibiotics (2,(14)(15)(16)(17).…”
Section: Introductionmentioning
confidence: 99%