scholarly journals Fat SIRAH: Coarse-grained phospholipids to explore membrane-protein dynamics

2019 ◽  
Author(s):  
Exequiel E. Barrera ◽  
Matías R. Machado ◽  
Sergio Pantano
Keyword(s):  
Membrane Protein ◽  
Effective Interaction ◽  
Coarse Grained ◽  
Single Amino Acid ◽  
Head Groups ◽  
Lipid Species ◽  
Good Reproduction ◽  
Consistent Manner ◽  
Coarse Grained Simulations ◽  
Chain Lengths

ABSTRACTTne capability to handle highly heterogeneous molecular assemblies in a consistent manner is among the greatest challenges faced when deriving simulation parameters. This is particularly the case for coarse-grained simulations in which chemical functional groups are lumped into effective interaction centers for which transferability between different chemical environments is not guaranteed. Here we introduce the parameterization of a set of CG phospholipids compatible with the latest version of the SIRAH force field for proteins. The newly introduced lipid species include different acylic chain lengths, partial unsaturation, as well as polar and acidic head groups that show a very good reproduction of structural membrane determinants, as areas per lipid, thickness, order parameter, etc., and their dependence with temperature. Simulation of membrane proteins showed unprecedented accuracy in the unbiased description of the thickness-dependent membrane-protein orientation in systems where this information is experimentally available (namely, the SarcoEndoplasmic Reticulum Calcium –SERCA-pump and its regulator Phospholamban). The interactions that lead to this faithful reproduction can be traced down to single amino acid-lipid interaction level and show full agreement with biochemical data present in the literature. Finally, the present parameterization is implemented in the GROMACS and AMBER simulation packages facilitating its use to a wide portion of the Biocomputing community.

scholarly journals Regulation of multispanning membrane protein topology via post-translational annealing

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Reid C Van Lehn ◽  
Bin Zhang ◽  
Thomas F Miller
Keyword(s):  
Membrane Protein ◽  
Annealing Process ◽  
Coarse Grained ◽  
Fully Integrated ◽  
Protein Topology ◽  
Membrane Protein Topology ◽  
C Terminus ◽  
Coarse Grained Simulations ◽  
Positively Charged

The canonical mechanism for multispanning membrane protein topogenesis suggests that protein topology is established during cotranslational membrane integration. However, this mechanism is inconsistent with the behavior of EmrE, a dual-topology protein for which the mutation of positively charged loop residues, even close to the C-terminus, leads to dramatic shifts in its topology. We use coarse-grained simulations to investigate the Sec-facilitated membrane integration of EmrE and its mutants on realistic biological timescales. This work reveals a mechanism for regulating membrane-protein topogenesis, in which initially misintegrated configurations of the proteins undergo post-translational annealing to reach fully integrated multispanning topologies. The energetic barriers associated with this post-translational annealing process enforce kinetic pathways that dictate the topology of the fully integrated proteins. The proposed mechanism agrees well with the experimentally observed features of EmrE topogenesis and provides a range of experimentally testable predictions regarding the effect of translocon mutations on membrane protein topogenesis.

scholarly journals Coarse-Grained Simulations of the Effects of Chain Length, Solvent Quality, and Chemical Defects on the Solution-Phase Morphology of MEH-PPV Conjugated Polymers

2012 ◽  
Vol 65 (5) ◽  
pp. 463 ◽  
Author(s):  
Ming Chiu ◽  
Tak W. Kee ◽  
David M. Huang
Keyword(s):  
Polymer Chains ◽  
Coarse Grained ◽  
Radius Of Gyration ◽  
Implicit Solvent ◽  
Coarse Grained Model ◽  
Solvent Quality ◽  
Defect Content ◽  
Coarse Grained Simulations ◽  
Chain Lengths ◽  
Poor Solvent

A mesoscale coarse-grained model of the conjugated polymer poly(2-methoxy-5-(2′-ethylhexyloxy)-1,4-phenylenevinylene) (MEH-PPV) in implicit solvent is developed. The model is parametrized to reproduce the local structure and dynamics of an atomistic simulation model and accounts for the effects of solvent quality and saturation chemical defects on the polymer structure. Polymers with defect concentrations of 0 to 10 % are simulated using Langevin dynamics in tetrahydrofuran (THF) and in a model poor solvent for chain lengths and solution concentrations used experimentally. The polymer chains are extended in THF and collapse into compact structures in the poor solvent. The radius of gyration decreases with defect content in THF and agrees quantitatively with experiment. The structures formed in poor solvent by chains with 300 monomer units change from toroidal to cylindrical with increasing defect content, while chains containing 1000 monomers form cylinders regardless of defect content. These results have implications for energy transfer in MEH-PPV.

Corrigendum to: Coarse-Grained Simulations of the Effects of Chain Length, Solvent Quality, and Chemical Defects on the Solution-Phase Morphology of MEH-PPV Conjugated Polymers

2013 ◽  
Vol 66 (4) ◽  
pp. 505
Author(s):  
Ming Chiu ◽  
Tak W. Kee ◽  
David M. Huang
Keyword(s):  
Polymer Chains ◽  
Coarse Grained ◽  
Radius Of Gyration ◽  
Implicit Solvent ◽  
Coarse Grained Model ◽  
Solvent Quality ◽  
Defect Content ◽  
Coarse Grained Simulations ◽  
Chain Lengths ◽  
Poor Solvent

A mesoscale coarse-grained model of the conjugated polymer poly(2-methoxy-5-(2'-ethylhexyloxy)-1,4-phenylenevinylene) (MEH-PPV) in implicit solvent is developed. The model is parametrized to reproduce the local structure and dynamics of an atomistic simulation model and accounts for the effects of solvent quality and saturation chemical defects on the polymer structure. Polymers with defect concentrations of 0 to 10 % are simulated using Langevin dynamics in tetrahydrofuran (THF) and in a model poor solvent for chain lengths and solution concentrations used experimentally. The polymer chains are extended in THF and collapse into compact structures in the poor solvent. The radius of gyration decreases with defect content in THF and agrees quantitatively with experiment. The structures formed in poor solvent by chains with 300 monomer units change from toroidal to cylindrical with increasing defect content, while chains containing 1000 monomers form cylinders regardless of defect content. These results have implications for energy transfer in MEH-PPV.

Specific protein–lipid interactions in membrane proteins

2005 ◽  
Vol 33 (5) ◽  
pp. 938-942 ◽  
Author(s):  
C. Hunte
Keyword(s):  
Membrane Proteins ◽  
Membrane Protein ◽  
Structural Integrity ◽  
Protein Structures ◽  
Specific Protein ◽  
Lipid Binding ◽  
Functional Roles ◽  
Lipid Interactions ◽  
Head Groups ◽  
Lipid Species

Many membrane proteins selectively bind defined lipid species. This specificity has an impact on correct insertion, folding, structural integrity and full functionality of the protein. How are these different tasks achieved? Recent advances in structural research of membrane proteins provide new information about specific protein–lipid interactions. Tightly bound lipids in membrane protein structures are described and general principles of the binding interactions are deduced. Lipid binding is stabilized by multiple non-covalent interactions from protein residues to lipid head groups and hydrophobic tails. Distinct lipid-binding motifs have been identified for lipids with defined head groups in membrane protein structures. The stabilizing interactions differ between the electropositive and electronegative membrane sides. The importance of lipid binding for vertical positioning and tight integration of proteins in the membrane, for assembly and stabilization of oligomeric and multisubunit complexes, for supercomplexes, as well as for functional roles are pointed out.

Microstructural morphology of sphingolipid dispersions as investigated by freeze-fracture EM

1995 ◽  
Vol 53 ◽  
pp. 944-945
Author(s):  
Vitthal S. Kulkarni ◽  
Wayne H. Anderson ◽  
Rhoderick E. Brown
Keyword(s):  
Acyl Chain ◽  
Biological Significance ◽  
Freeze Fracture ◽  
Fatty Acyl ◽  
Fatty Acyl Moiety ◽  
Aqueous Dispersions ◽  
Head Groups ◽  
Lipid Species ◽  
Microstructural Morphology ◽  
Layer Chromatography

The biological significance of the sphingomyelins (SM) and monoglycosylated sphingolipids like galactosylceramides (GalCer) are well documented Our recent investigation showed tubular bilayers in the aqueous dispersions of N-nervonoyl GalCer [N-(24:lΔ15,cls) GalCer] (a major fatty acyl moiety of natural GalCer). To determine the influence of lipid head groups on the resulting mesophasic morphology, we investigated microstructural self-assemblies of N-nervonoyl-SM [N-(24:1 Δ15,cls) SM; the second most abundant sphingomyelin in mammalian cell membranes], 1- palmitoyl-2-nervonoyl phosphatidylcholine [PNPC] (the lipid species with the same acyl chain configuration as in N-(24: 1) GalCer) and also compared it with egg-SM by freeze-fracture EM.Procedures for synthesizing and purifying N-(24:1) GalCer, N-(24:1) SM, and PNPC have been reported . Egg-SM was purchased from Avanti Polar Lipids, Alabaster AL. All lipids were >99% pure as checked by thin layer chromatography. Lipid dispersions were prepared by hydrating dry lipid with phosphate buffer (pH 6.6) at 80-90°C (3-5 min), vigorously vortexing (1 min) and repeating this procedure for three times prior to three freeze-thaw cycles.

Grand-Reaction Method for Simulations of Ionization Equilibria and Ion Partitioning in a Broad Range of pH and Ionic Strength

2019 ◽  
Author(s):  
Jonas Landsgesell ◽  
Oleg Rud ◽  
Pascal Hebbeker ◽  
Raju Lunkad ◽  
Peter Košovan ◽  
...  
Keyword(s):  
Mean Field ◽  
Coarse Grained ◽  
Reactive System ◽  
Acid Base ◽  
Buffer Solution ◽  
Reaction Method ◽  
Ionization Equilibria ◽  
Coarse Grained Simulations ◽  
Ph Range ◽  
Weak Polyelectrolytes

We introduce the grand-reaction method for coarse-grained simulations of acid-base equilibria in a system coupled to a reservoir at a given pH and concentration of added salt. It can be viewed as an extension of the constant-pH method and the reaction ensemble, combining explicit simulations of reactions within the system, and grand-canonical exchange of particles with the reservoir. Unlike the previously introduced methods, the grand-reaction method is applicable to acid-base equilibria in the whole pH range because it avoids known artifacts. However, the method is more general, and can be used for simulations of any reactive system coupled to a reservoir of a known composition. To demonstrate the advantages of the grand-reaction method, we simulated a model system: A solution of weak polyelectrolytes in equilibrium with a buffer solution. By carefully accounting for the exchange of all constituents, the method ensures that all chemical potentials are equal in the system and in the multi-component reservoir. Thus, the grand-reaction method is able to predict non-monotonic swelling of weak polyelectrolytes as a function of pH, that has been known from mean-field predictions and from experiments but has never been observed in coarse-grained simulations. Finally, we outline possible extensions and further generalizations of the method, and provide a set of guidelines to enable safe usage of the method by a broad community of users.<br><br>

Simulation studies of the interactions between membrane proteins and detergents

2005 ◽  
Vol 33 (5) ◽  
pp. 910-912 ◽  
Author(s):  
P.J. Bond ◽  
J. Cuthbertson ◽  
M.S.P. Sansom
Keyword(s):  
Membrane Proteins ◽  
Membrane Protein ◽  
Self Assembly ◽  
Kinetic Mechanism ◽  
Coarse Grained ◽  
Simulation Studies ◽  
High Resolution Data ◽  
Biologically Relevant ◽  
Structure And Dynamics ◽  
Detergent Interactions

Interactions between membrane proteins and detergents are important in biophysical and structural studies and are also biologically relevant in the context of folding and transport. Despite a paucity of high-resolution data on protein–detergent interactions, novel methods and increased computational power enable simulations to provide a means of understanding such interactions in detail. Simulations have been used to compare the effect of lipid or detergent on the structure and dynamics of membrane proteins. Moreover, some of the longest and most complex simulations to date have been used to observe the spontaneous formation of membrane protein–detergent micelles. Common mechanistic steps in the micelle self-assembly process were identified for both α-helical and β-barrel membrane proteins, and a simple kinetic mechanism was proposed. Recently, simplified (i.e. coarse-grained) models have been utilized to follow long timescale transitions in membrane protein–detergent assemblies.

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