scholarly journals NRas slows the rate at which a model lipid bilayer phase separates

2014 ◽  
Vol 169 ◽  
pp. 209-223 ◽  
Author(s):  
Elizabeth Jefferys ◽  
Mark S. P. Sansom ◽  
Philip W. Fowler
Keyword(s):  
Lipid Bilayer ◽  
Cell Signalling ◽  
Line Tension ◽  
Structural Data ◽  
Coarse Grained ◽  
Ras Proteins ◽  
C Terminus ◽  
Ras Family ◽  
Multiple Copies ◽  
Dynamics Simulations

The Ras family of small membrane-associated GTP-ases are important components in many different cell signalling cascades. They are thought to cluster on the cell membrane through association with cholesterol-rich nanodomains. This process remains poorly understood. Here we test the effect of adding multiple copies of NRas, one of the canonical Ras proteins, to a three-component lipid bilayer that rapidly undergoes spinodal decomposition (i.e.unmixing), thereby creating ordered and disordered phases. Coarse-grained molecular dynamics simulations of a large bilayer containing 6000 lipids, with and without protein, are compared. NRas preferentially localises to the interface between the domains and slows the rate at which the domains grow. We infer that this doubly-lipidated cell signalling protein is reducing the line tension between the ordered and disordered regions. This analysis is facilitated by our use of techniques borrowed from image-processing. The conclusions above are contingent upon several assumptions, including the use of a model lipid with doubly unsaturated tails and the limited structural data available for the C-terminus of NRas, which is where the lipid anchors are found.

Coarse-grained simulation: a high-throughput computational approach to membrane proteins

2008 ◽  
Vol 36 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Mark S.P. Sansom ◽  
Kathryn A. Scott ◽  
Peter J. Bond
Keyword(s):  
Membrane Proteins ◽  
Lipid Bilayer ◽  
High Throughput ◽  
Protein Interactions ◽  
Coarse Grained ◽  
Atomistic Simulations ◽  
Lactose Permease ◽  
Coarse Grained Simulations ◽  
Dynamics Simulations ◽  
Good Agreement

An understanding of the interactions of membrane proteins with a lipid bilayer environment is central to relating their structure to their function and stability. A high-throughput approach to prediction of membrane protein interactions with a lipid bilayer based on coarse-grained Molecular Dynamics simulations is described. This method has been used to develop a database of CG simulations (coarse-grained simulations) of membrane proteins (http://sbcb.bioch.ox.ac.uk/cgdb). Comparison of CG simulations and AT simulations (atomistic simulations) of lactose permease reveals good agreement between the two methods in terms of predicted lipid headgroup contacts. Both CG and AT simulations predict considerable local bilayer deformation by the voltage sensor domain of the potassium channel KvAP.

scholarly journals Ionic transport through a protein nanopore: a Coarse-Grained Molecular Dynamics Study

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Nathalie Basdevant ◽  
Delphine Dessaux ◽  
Rosa Ramirez
Keyword(s):  
Molecular Dynamics ◽  
Lipid Bilayer ◽  
Electric Fields ◽  
Ionic Transport ◽  
Stationary Regime ◽  
Coarse Grained ◽  
Experimental Conditions ◽  
Current Saturation ◽  
Order Of Magnitude ◽  
Dynamics Simulations

Abstract The MARTINI coarse-grained (CG) force field is used to test the ability of CG models to simulate ionic transport through protein nanopores. The ionic conductivity of CG ions in solution was computed and compared with experimental results. Next, we studied the electrostatic behavior of a solvated CG lipid bilayer in salt solution under an external electric field. We showed this approach correctly describes the experimental conditions under a potential bias. Finally, we performed CG molecular dynamics simulations of the ionic transport through a protein nanopore (α-hemolysin) inserted in a lipid bilayer, under different electric fields, for 2–3 microseconds. The resulting I − V curve is qualitatively consistent with experiments, although the computed current is one order of magnitude smaller. Current saturation was observed for potential biases over ±350 mV. We also discuss the time to reach a stationary regime and the role of the protein flexibility in our CG simulations.

A COARSE-GRAINED MODEL OF MONOOLEIN: COMPARISON WITH THE ATOMISTIC MODEL

2009 ◽  
Vol 08 (01n02) ◽  
pp. 169-173
Author(s):  
J. H. KIM ◽  
S. H. CHOI ◽  
D. H. JUNG ◽  
C. S. CHO ◽  
Y. J. CHOI
Keyword(s):  
Molecular Dynamics ◽  
Lipid Bilayer ◽  
Dissipative Particle Dynamics ◽  
Dynamics Simulation ◽  
Coarse Grained ◽  
Atomistic Model ◽  
Coarse Grained Model ◽  
Cosmetic Industry ◽  
Dynamics Simulations ◽  
Potential Parameters

Monoolein (2,3-dihydroxypropyl (Z)-octadec-9-enoate) is one of the monoacylglycerol and has been studied for various applications in food, pharmaceutical, and cosmetic industry. Those applications make use of the phase behavior of monoolein. In order to understand the lipid bilayer phase of monoolein in mesoscale, a coarse-grained model has been built and tested in this work. The monoolein molecule was represented by two hydrophilic heads and six hydrophobic tails. The three water molecules were also represented as one bead. For comparison, the atomistic model has also been used for molecular dynamics simulation on the lipid bilayer phase in isothermal-isobaric (NPT) ensemble. The interaction and bond bending potential parameters for dissipative particle dynamics (DPD) were obtained with molecular dynamics simulations on lipid bilayer in water. And we also obtained the interaction parameters of the coarse-grained model, which agree well with the atomistic model. We compared the simulated phases using the coarse-grained model with using the atomistic model. With these parameters, we successfully reproduced the lamella phase of monoolein in DPD simulations.

scholarly journals Multiple interactions between an Arf/GEF complex and charged lipids determine activation kinetics on the membrane

2017 ◽  
Vol 114 (43) ◽  
pp. 11416-11421 ◽  
Author(s):  
Deepti Karandur ◽  
Agata Nawrotek ◽  
John Kuriyan ◽  
Jacqueline Cherfils
Keyword(s):  
Lipid Bilayer ◽  
Membrane Trafficking ◽  
Structural Model ◽  
High Efficiency ◽  
Structural Data ◽  
Lipid Binding ◽  
Small Gtpases ◽  
Coarse Grained ◽  
Nucleotide Exchange ◽  
Ph Domain

Lipidated small GTPases and their regulators need to bind to membranes to propagate actions in the cell, but an integrated understanding of how the lipid bilayer exerts its effect has remained elusive. Here we focused on ADP ribosylation factor (Arf) GTPases, which orchestrate a variety of regulatory functions in lipid and membrane trafficking, and their activation by the guanine-nucleotide exchange factor (GEF) Brag2, which controls integrin endocytosis and cell adhesion and is impaired in cancer and developmental diseases. Biochemical and structural data are available that showed the exceptional efficiency of Arf activation by Brag2 on membranes. We determined the high-resolution crystal structure of unbound Brag2 containing the GEF (Sec7) and membrane-binding (pleckstrin homology) domains, revealing that it has a constitutively active conformation. We used this structure to analyze the interaction of uncomplexed Brag2 and of the myristoylated Arf1/Brag2 complex with a phosphatidylinositol bisphosphate (PIP2) -containing lipid bilayer, using coarse-grained molecular dynamics. These simulations revealed that the system forms a close-packed, oriented interaction with the membrane, in which multiple PIP2 lipids bind the canonical lipid-binding site and unique peripheral sites of the PH domain, the Arf GTPase and, unexpectedly, the Sec7 domain. We cross-validated these predictions by reconstituting the binding and kinetics of Arf and Brag2 in artificial membranes. Our coarse-grained structural model thus suggests that the high efficiency of Brag2 requires interaction with multiple lipids and a well-defined orientation on the membrane, resulting in a local PIP2 enrichment, which has the potential to signal toward the Arf pathway.

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