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 Lipid-protein interactions are unique fingerprints for membrane proteins

2017 ◽  
Author(s):  
Valentina Corradi ◽  
Eduardo Mendez-Villuendas ◽  
Helgi I. Ingólfsson ◽  
Ruo-Xu Gu ◽  
Iwona Siuda ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Protein Interactions ◽  
Cell Membranes ◽  
Spatiotemporal Resolution ◽  
Lipid Dynamics ◽  
Lipid Species ◽  
Lipid Environment ◽  
Lipid Protein Interactions ◽  
Dynamics Simulations ◽  
Asymmetrically Distributed

ABSTRACTCell membranes contain hundreds of different proteins and lipids in an asymmetric arrangement. Understanding the lateral organization principles of these complex mixtures is essential for life and health. However, our current understanding of the detailed organization of cell membranes remains rather elusive, owing to the lack of experimental methods suitable for studying these fluctuating nanoscale assemblies of lipids and proteins with the required spatiotemporal resolution. Here, we use molecular dynamics simulations to characterize the lipid environment of ten membrane proteins. To provide a realistic lipid environment, the proteins are embedded in a model plasma membrane, where more than 60 lipid species are represented, asymmetrically distributed between leaflets. The simulations detail how each protein modulates its local lipid environment through local lipid composition, thickness, curvature and lipid dynamics. Our results provide a molecular glimpse of the complexity of lipid-protein interactions, with potentially far reaching implications for the overall organization of the cell membrane.

Extension of the UNRES Coarse-Grained Force Field to Membrane Proteins in the Lipid Bilayer

2019 ◽  
Vol 123 (37) ◽  
pp. 7829-7839
Author(s):  
Karolina Ziȩba ◽  
Magdalena Ślusarz ◽  
Rafał Ślusarz ◽  
Adam Liwo ◽  
Cezary Czaplewski ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Force Field ◽  
Lipid Bilayer ◽  
Coarse Grained

scholarly journals Ganglioside-Lipid and Ganglioside-Protein Interactions Revealed by Coarse-Grained and Atomistic Molecular Dynamics Simulations

2016 ◽  
Vol 121 (15) ◽  
pp. 3262-3275 ◽  
Author(s):  
Ruo-Xu Gu ◽  
Helgi I. Ingólfsson ◽  
Alex H. de Vries ◽  
Siewert J. Marrink ◽  
D. Peter Tieleman
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Protein Interactions ◽  
Coarse Grained ◽  
Dynamics Simulations

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.

Molecular simulations and lipid–protein interactions: potassium channels and other membrane proteins

2005 ◽  
Vol 33 (5) ◽  
pp. 916-920 ◽  
Author(s):  
M.S.P. Sansom ◽  
P.J. Bond ◽  
S.S. Deol ◽  
A. Grottesi ◽  
S. Haider ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Binding Site ◽  
Protein Interactions ◽  
Outer Membrane Proteins ◽  
Lipid Binding ◽  
Potassium Channel Kcsa ◽  
Head Groups ◽  
Arginine Residues ◽  
Lipid Protein Interactions ◽  
Dynamics Simulations

Molecular dynamics simulations may be used to probe the interactions of membrane proteins with lipids and with detergents at atomic resolution. Examples of such simulations for ion channels and for bacterial outer membrane proteins are described. Comparison of simulations of KcsA (an α-helical bundle) and OmpA (a β-barrel) reveals the importance of two classes of side chains in stabilizing interactions with the head groups of lipid molecules: (i) tryptophan and tyrosine; and (ii) arginine and lysine. Arginine residues interacting with lipid phosphate groups play an important role in stabilizing the voltage-sensor domain of the KvAP channel within a bilayer. Simulations of the bacterial potassium channel KcsA reveal specific interactions of phosphatidylglycerol with an acidic lipid-binding site at the interface between adjacent protein monomers. A combination of molecular modelling and simulation reveals a potential phosphatidylinositol 4,5-bisphosphate-binding site on the surface of Kir6.2.

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