scholarly journals Lipoprotein-Induced Increases in Cholesterol and 7-Ketocholesterol Result in Opposite Molecular-Scale Biophysical Effects on Membrane Structure

2021 ◽  
Vol 8 ◽  
Author(s):  
Manuela A.A. Ayee ◽  
Irena Levitan
Keyword(s):  
Membrane Structure ◽  
Dynamic Properties ◽  
Lateral Diffusion ◽  
Coarse Grained ◽  
Bilayer Membranes ◽  
Lipid Packing ◽  
Molecular Scale ◽  
Dynamics Simulations ◽  
Biophysical Effects ◽  
Lateral Area

Under hypercholesterolemic conditions, exposure of cells to lipoproteins results in a subtle membrane increase in the levels of cholesterol and 7-ketocholesterol, as compared to normal conditions. The effect of these physiologically relevant concentration increases on multicomponent bilayer membranes was investigated using coarse-grained molecular dynamics simulations. Significant changes in the structural and dynamic properties of the bilayer membranes resulted from these subtle increases in sterol levels, with both sterol species inducing decreases in the lateral area and inhibiting lateral diffusion to varying extents. Cholesterol and 7-ketocholesterol, however, exhibited opposite effects on lipid packing and orientation. The results from this study indicate that the subtle increases in membrane sterol levels induced by exposure to lipoproteins result in molecular-scale biophysical perturbation of membrane structure.

scholarly journals Bilayer sheet protrusions and budding from bilayer membranes induced by hydrolysis and condensation reactions

Soft Matter ◽  
2018 ◽  
Vol 14 (8) ◽  
pp. 1397-1407 ◽  
Author(s):  
Koh M. Nakagawa ◽  
Hiroshi Noguchi
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Coarse Grained ◽  
Bilayer Membranes ◽  
Condensation Reactions ◽  
Amphiphilic Molecules ◽  
Hydrolysis And Condensation ◽  
Shape Transformations ◽  
Dynamics Simulations ◽  
Coarse Grained Molecular Dynamics

Shape transformations of flat bilayer membranes and vesicles induced by hydrolysis and condensation reactions of amphiphilic molecules are studied using coarse-grained molecular dynamics simulations.

Interaction of fullerene chains and a lipid membrane via computer simulations

RSC Advances ◽  
2014 ◽  
Vol 4 (57) ◽  
pp. 30215-30220 ◽  
Author(s):  
Wen-de Tian ◽  
Kang Chen ◽  
Yu-qiang Ma
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Computer Simulations ◽  
Membrane Structure ◽  
Lipid Membrane ◽  
Coarse Grained ◽  
Structure Dynamics ◽  
Dynamics Simulations ◽  
Fullerene Polymers ◽  
Coarse Grained Molecular Dynamics

Coarse-grained molecular dynamics simulations were employed to study the fullerene polymers with various functionalization degrees interacting with the DPPC membrane. Structure, dynamics, and thermodynamics of systems were analyzed.

scholarly journals Composition fluctuations in lipid bilayers

2016 ◽  
Author(s):  
Svetlana Baoukina ◽  
Dmitri Rozmanov ◽  
D. Peter Tieleman
Keyword(s):  
Lipid Bilayers ◽  
Liquid Crystalline ◽  
Dynamic Properties ◽  
Coarse Grained ◽  
Gradual Transition ◽  
Dynamic Heterogeneity ◽  
Two Phase ◽  
Unsaturated Lipids ◽  
Dynamics Simulations ◽  
Composition Fluctuations

AbstractLipid bilayers constitute the basis of biological membranes. Understanding lipid mixing and phase behavior can provide important insights into membrane lateral organization (the “raft” hypothesis). Here we investigate model lipid bilayers below and above their miscibility transition temperatures. Molecular dynamics simulations with the MARTINI coarse-grained force field are employed to model bilayers on a length scale approaching 100 nm and a time scale of tens of microseconds. Using a binary mixture of saturated and unsaturated lipids, and a ternary mixture of a saturated lipid, an unsaturated lipid and cholesterol we reproduce the coexistence of liquid-crystalline and gel, as well as liquid-ordered and liquid-disordered phases. By raising the temperature or adding hybrid lipids (with a saturated and an unsaturated chain), we induce a gradual transition from a two-phase to a one-phase state. We characterize the evolution of bilayer properties along this transition. Domains of coexisting phases change to dynamic heterogeneity with local ordering and compositional de-mixing. We analyze the structural and dynamic properties of domains, sizes and lifetimes of composition fluctuations, and calculate the in-plane structure factors.

scholarly journals Impact of emerging mutations on the dynamic properties the SARS-CoV-2 main protease: an in silico investigation

2020 ◽  
Author(s):  
Olivier Sheik Amamuddy ◽  
Gennady M Verkhivker ◽  
Ozlem Tastan Bishop
Keyword(s):  
Dynamic Properties ◽  
Coarse Grained ◽  
World Health ◽  
Enzyme Dynamics ◽  
Enzymatic Function ◽  
Main Protease ◽  
Viral Maturation ◽  
Dynamics Simulations ◽  
Global Threat

The new coronavirus (SARS-CoV-2) is a global threat to world health and its economy. Its main protease (Mpro), which functions as a dimer, cleaves viral precursor proteins in the process of viral maturation. It is a good candidate for drug development owing to its conservation and the absence of a human homolog. An improved understanding of the protein behaviour can accelerate the discovery of effective therapies in order to reduce mortality. 100 ns all-atom molecular dynamics simulations of 50 homology modelled mutant Mpro dimers were performed at pH 7 from filtered sequences obtained from the GISAID database. Protease dynamics were analysed using RMSD, RMSF, Rg, the averaged betweenness centrality and geometry calculations. Domains from each Mpro protomer were found to generally have independent motions, while the dimer-stabilising N-finger region was found to be flexible in most mutants. A mirrored interprotomer pocket was found to be correlated to the catalytic site using compaction dynamics, and can be a potential allosteric target. The high number of titratable amino acids of Mpro may indicate an important role of pH on enzyme dynamics, as previously reported for SARS-CoV. Independent coarse-grained Monte Carlo simulations suggest a link between rigidity/mutability and enzymatic function.

What can we Learn from Molecular Dynamics Simulations of Macromolecular Liquids?

1989 ◽  
Vol 177 ◽  
Author(s):  
Gary S. Grest ◽  
Kurt Kremer ◽  
Michael Murat
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Dynamic Properties ◽  
Star Polymers ◽  
Coarse Grained ◽  
Linear Polymers ◽  
Coarse Grained Model ◽  
Percolation Clusters ◽  
Large Systems ◽  
Dynamics Simulations

ABSTRACTWe describe how molecular dynamics simulations for a relatively simple coarse grained model can be very useful for investigating the static and dynamic properties of polymers and other macromolecular liquids. We show that it is important to use a simplified coarse grained model instead of a detailed microscopic model if one is interested in studying on modern supercomputers large systems which also relax slowly. As examples we present results for isolated star polymers with f-arms and diluted gelation/percolation clusters. We find in agreement with recent neutron scattering experiments that diluted percolation clusters swell and that their fractal dimension is reduced from 2.5 to 2. We also discuss our results for a dense melt of entangled linear polymers to show that the method is effective at high density. Our results for the entangled melt cover the crossover from Rouse to reptation and strongly support the concept of reptation.

scholarly journals Spider Toxin SNX-482 Gating Modifier Spontaneously Partitions in the Membrane Guided by Electrostatic Interactions

2021 ◽  
Author(s):  
Guido Mellado ◽  
Jose Antonio Garate ◽  
Alan Neely
Keyword(s):  
Aqueous Phase ◽  
Electrostatic Interactions ◽  
Lateral Diffusion ◽  
Critical Factor ◽  
Coarse Grained ◽  
Spider Toxin ◽  
Order Of Magnitude ◽  
Direct Binding ◽  
Dynamics Simulations ◽  
Binding Mechanisms

Spider toxin SNX-482 is a cysteine-rich peptide that interferes with calcium channel activity by binding to voltage-sensing domains of CaV2.3 subtype. Two general binding mechanisms are present in nature: direct binding from the aqueous phase or through lateral diffusion from the membrane, the so-called reduction in dimensionality mechanism. In this work, via coarse-grained and atomistic molecular dynamics simulations, we have systematically studied the spontaneous partitioning of SNX-482 with membranes of different anionic compositions and explored via diffusional analysis both binding mechanisms. Our simulations revealed a conserved protein patch that inserts within the membrane, a preference for binding towards partially negatively charged membranes, and that electrostatics drives membrane binding. Finally, diffusivity calculations showed that the toxin diffusion along the membrane plane is an order of magnitude slower than the aqueous phase suggesting that the critical factor in determin-ing the SNX-482-CaV2.3 binding mechanism is the affinity between the membrane and SNX-482

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