Molecular Simulations of Gram-Negative Bacterial Membranes: A Vignette of Some Recent Successes

Parkin, Jamie; Chavent, Matthieu; Khalid, Syma

doi:10.1016/j.bpj.2015.06.050

Cited by 46 publications

(28 citation statements)

References 75 publications

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“…The OM is a unique asymmetrical bilayer composed of LPS molecules in the outer leaflet and a mixture of zwitterionic and anionic phospholipids in the inner leaflet . The inner membrane is more or less symmetric, and both leaflets closely resemble the inner leaflet of the OM in terms of the phospholipid composition . Given that modification of these membranes is one of the ways that bacteria achieve resistance to our current arsenal of antibiotics, studying the relationship between the membrane/membrane proteins and drugs is imperative for the rational design of novel antibiotics .…”

Section: Introductionmentioning

confidence: 99%

CHARMM‐GUI Martini Maker for modeling and simulation of complex bacterial membranes with lipopolysaccharides

et al. 2017

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A complex cell envelope, composed of a mixture of lipid types including complex lipopolysaccharides, protects bacteria from the external environment. Clearly, the proteins embedded within the various components of the cell envelope have an intricate relationship with their local environment. Therefore, to obtain meaningful results, molecular simulations need to mimic as far as possible this chemically heterogeneous system. However, setting up such systems for computational studies is far from trivial, and consequently the vast majority of simulations of outer membrane proteins still rely on oversimplified phospholipid membrane models. This work presents an update of CHARMM-GUI Martini Maker for coarse-grained modeling and simulation of complex bacterial membranes with lipopolysaccharides. The qualities of the outer membrane systems generated by Martini Maker are validated by simulating them in bilayer, vesicle, nanodisc, and micelle environments (with and without outer membrane proteins) using the Martini force field. We expect this new feature in Martini Maker to be a useful tool for modeling large, complicated bacterial outer membrane systems in a user-friendly manner.

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Section: Introductionmentioning

confidence: 99%

CHARMM‐GUI Martini Maker for modeling and simulation of complex bacterial membranes with lipopolysaccharides

et al. 2017

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“…nevertheless they have already proven to be a successful addition to the toolkit for studying biological membranes and the proteins that are associated with them 39,40 . Currently MD simulations are routinely used to study the evolution of a molecular system on microsecond timescales (we note that timescales that exceed these have been reported, but these usually require custom-built hardware) [41][42][43] .…”

Section: Opportunity For Use In Molecular Simulationmentioning

confidence: 99%

Encapsulated membrane proteins: A simplified system for molecular simulation

Lee¹,

Khalid²,

Pollock³

et al. 2016

Biochimica et Biophysica Acta (BBA) - Biomembranes

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A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 2Over the past 50 years there has been considerable progress in our understanding of biomolecular interactions at an atomic level. This in turn has allowed molecular simulation methods employing full atomistic modeling at ever larger scales to develop. However, some challenging areas still remain where there is either a lack of atomic resolution structures or where the simulation system is inherentlycomplex.An area where both challenges are present is that of membranes containing membrane proteins. In this review we analyse a new practical approach to membrane protein study that offers a potential new route to high resolution structures and the possibility to simplify simulations.These new approaches collectively recognise that preservation of the interaction between the membrane protein and the lipid bilayer is often essential to maintain structure and function. The new methods preserve these interactions by producing nano-scale disc shaped particles that include bilayer and the chosen protein. Currently two approaches lead in this area: the MSP system that relies on peptides to stabilise the discs, and SMALPs where an amphipathic styrene maleic acid copolymer is used. Both methods greatly enable protein production and hence have the potential to accelerate atomic resolution structure determination as well as providing a simplified format for simulations of membrane protein dynamics.

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“…Despite their importance, the experimental study of LPSs and OMPs is challenging. Molecular Dynamics (MD) simulations are a useful tool for modeling the structure and dynamics of biological macromolecules and have been routinely used in the study of biological membranes and membrane proteins, including OMPs . However, while the construction of membrane models with phospholipids has become a rudimentary process, designing MD simulation systems for OMs is not as straightforward, mostly due to the increased complexity of LPSs compared to standard lipids.…”

Section: Introductionmentioning

confidence: 99%

The gram‐negative outer membrane modeler: Automated building of lipopolysaccharide‐rich bacterial outer membranes in four force fields

2019

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Outer membranes are a crucial component of Gram‐negative bacteria, containing standard lipids in their inner leaflet, lipopolysaccharides (LPSs) in their outer leaflet, and transmembrane β‐barrels known as outer membrane proteins (OMPs). OMPs regulate functions such as substrate transport and cell movement, while LPSs act as a protective barrier for bacteria and can cause toxic reactions in humans. However, the experimental study of outer membranes is challenging. Molecular dynamics simulations are often used for the computational study of membrane systems, but the preparation of complex, LPS‐rich outer membranes is not straightforward. The Gram‐Negative Outer Membrane Modeler (GNOMM) is an automated pipeline for preparing simulation systems of OMPs embedded in LPS‐containing membranes in four different force fields. Given the physiological and clinical importance of outer membranes and their components, GNOMM can be a useful tool in the study of their structure, function, and implications in diseases. GNOMM is available at http://bioinformatics.biol.uoa.gr/GNOMM. © 2019 Wiley Periodicals, Inc.

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Molecular Simulations of Gram-Negative Bacterial Membranes: A Vignette of Some Recent Successes

Cited by 46 publications

References 75 publications

CHARMM‐GUI Martini Maker for modeling and simulation of complex bacterial membranes with lipopolysaccharides

CHARMM‐GUI Martini Maker for modeling and simulation of complex bacterial membranes with lipopolysaccharides

Encapsulated membrane proteins: A simplified system for molecular simulation

The gram‐negative outer membrane modeler: Automated building of lipopolysaccharide‐rich bacterial outer membranes in four force fields

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