scholarly journals Atomistic Molecular Dynamics Simulations of Trioleoylglycerol – Phospholipid Membrane Systems

2020 ◽  
Author(s):  
Mirza Ahmed Hammad ◽  
Hafiza Minal Akram ◽  
Muhammad Sohail Raza
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Lipid Droplets ◽  
Membrane System ◽  
Bilayer Membrane ◽  
Coarse Grained ◽  
Phospholipid Membrane ◽  
Software Suite ◽  
Future Studies ◽  
Dynamics Simulations

AbstractAdiposomes are phospholipid coated triacylglyceride particles that serve as structural models of the fat storage compartments of cells, known as lipid droplets (LDs); however, unlike LDs, they do not carry proteins. There is a deficit of available methods and experimental data regarding the internal packing of the adiposomes, and computer simulations offer a promising way to pinpoint the molecular arrangements within these structures. However, in the absence of a triacylglycerol-specific atomic forcefield, thus far, all adiposome/LD simulations have been performed with the coarse grained/united atom forcefields. Yet it is desirable to model the phospholipid/triacylglycerol interface with atomic resolution. In the present study, we first prepared a 2-monooleoylglycerol (MOG) forcefield which was then used to build a trioleoylglycerol (TOG) forcefield by the modular approach of the AMBER software suite. TOG bilayer membrane (2L) systems were modelled from two different initial conformations; TOG3 and TOG2:1. The simulations revealed that TOG2:1 is the most populated conformation in TOG membranes, irrespective of the starting conformation. Some other parameter optimizations were performed for TOG membranes based on which adiposome mimicking tetralayer membrane system (4L) was prepared with a TOG bilayer at core surrounded by two DOPC leaflets. The 4L membranes were stable throughout the simulations, however it was observed that a small amount of cations and water diffused from surface to the TOG core of the membrane. Based on these results a TAG-packing model was also developed. It is expected that the availability of MOG forcefield will equip future studies with a framework for molecular dynamics simulations of adiposomes/LDs.

scholarly journals How does temperature affect the dynamics of SARS-CoV-2 M proteins? Insights from Molecular Dynamics Simulations

2021 ◽  
Author(s):  
Soumya Lipsa Rath ◽  
Madhusmita Tripathy ◽  
Nabanita Mandal
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Membrane Lipids ◽  
Membrane System ◽  
Host Cells ◽  
Coarse Grained ◽  
M Protein ◽  
Effect Of Temperature ◽  
M Proteins ◽  
Dynamics Simulations

Enveloped viruses, in general, have several transmembrane proteins and glycoproteins, which assist the virus in entry and attachment onto the host cells. These proteins also play a significant role in determining the shape and size of the newly formed virus particles. The lipid membrane and the embedded proteins affect each other in non-trivial ways during the course of the viral life cycle. Unravelling the nature of the protein-protein and protein-lipid interactions, under various environmental and physiological conditions, could therefore prove to be crucial in development of therapeutics. Here, we study the M protein of SARS-CoV-2 to understand the effect of temperature on the properties of the protein-membrane system. The membrane embedded dimeric M proteins were studied using atomistic and coarse-grained molecular dynamics simulations at temperatures ranging between 10 and 50 ˚C. While temperature induced fluctuations should be monotonic, we observe a steady rise in the protein dynamics up to 40 ˚C, beyond which it surprisingly reverts back to the low temperature behaviour. Detailed investigation reveals disordering of the membrane lipids in the presence of the protein, which induces additional curvature around the transmembrane region. Coarse-grained simulations indicate temperature dependent aggregation of M protein dimers. Our study clearly indicates that the dynamics of membrane lipids and integral M protein of SARS-CoV-2 enables it to better associate and aggregate only at a certain temperature range (i.e., ~30 to 40 ˚C). This can have important implications in the protein aggregation and subsequent viral budding/fission processes.   

Parameterization of Divalent Cations for Coarse-Grained Simulations

2020 ◽  
Author(s):  
Florencia Klein ◽  
Daniela Cáceres-Rojas ◽  
Monica Carrasco ◽  
Juan Carlos Tapia ◽  
Julio Caballero ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Metal Ions ◽  
Molecular Dynamics Simulations ◽  
Divalent Cations ◽  
Computational Cost ◽  
Data Bank ◽  
Coarse Grained ◽  
Interaction Parameters ◽  
Dynamics Simulations ◽  
Dynamical Description

<p>Although molecular dynamics simulations allow for the study of interactions among virtually all biomolecular entities, metal ions still pose significant challenges to achieve an accurate structural and dynamical description of many biological assemblies. This is particularly the case for coarse-grained (CG) models. Although the reduced computational cost of CG methods often makes them the technique of choice for the study of large biomolecular systems, the parameterization of metal ions is still very crude or simply not available for the vast majority of CG- force fields. Here, we show that incorporating statistical data retrieved from the Protein Data Bank (PDB) to set specific Lennard-Jones interactions can produce structurally accurate CG molecular dynamics simulations. Using this simple approach, we provide a set of interaction parameters for Calcium, Magnesium, and Zinc ions, which cover more than 80% of the metal-bound structures reported on the PDB. Simulations performed using the SIRAH force field on several proteins and DNA systems show that using the present approach it is possible to obtain non-bonded interaction parameters that obviate the use of topological constraints. </p>

scholarly journals Variation of Interaction Zone Size For The Target Design of 2D Supramolecular Networks

2021 ◽  
Author(s):  
Łukasz Piotr Baran ◽  
Wojciech Rżysko ◽  
Dariusz Tarasewicz
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Self Assembly ◽  
The Self ◽  
Coarse Grained ◽  
Zone Size ◽  
Interaction Zone ◽  
Supramolecular Networks ◽  
Dynamics Simulations ◽  
Target Design

In this study we have performed extensive coarse-grained molecular dynamics simulations of the self-assembly of tetra-substituted molecules. We have found that such molecules are able to form a variety of...

scholarly journals Molecular dynamics simulations and experimental studies reveal differential permeability of withaferin-A and withanone across the model cell membrane

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Renu Wadhwa ◽  
Neetu Singh Yadav ◽  
Shashank P. Katiyar ◽  
Tomoko Yaguchi ◽  
Chohee Lee ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Cell Membrane ◽  
Molecular Dynamics Simulations ◽  
Experimental Studies ◽  
Bilayer Membrane ◽  
Withaferin A ◽  
Head Group ◽  
Polar Head Group ◽  
Natural Drugs ◽  
Dynamics Simulations

AbstractPoor bioavailability due to the inability to cross the cell membrane is one of the major reasons for the failure of a drug in clinical trials. We have used molecular dynamics simulations to predict the membrane permeability of natural drugs—withanolides (withaferin-A and withanone) that have similar structures but remarkably differ in their cytotoxicity. We found that whereas withaferin-A, could proficiently transverse through the model membrane, withanone showed weak permeability. The free energy profiles for the interaction of withanolides with the model bilayer membrane revealed that whereas the polar head group of the membrane caused high resistance for the passage of withanone, the interior of the membrane behaves similarly for both withanolides. The solvation analysis further revealed that the high solvation of terminal O5 oxygen of withaferin-A was the major driving force for its high permeability; it interacted with the phosphate group of the membrane that led to its smooth passage across the bilayer. The computational predictions were tested by raising and recruiting unique antibodies that react to withaferin-A and withanone. The time-lapsed analyses of control and treated cells demonstrated higher permeation of withaferin-A as compared to withanone. The concurrence between the computation and experimental results thus re-emphasised the use of computational methods for predicting permeability and hence bioavailability of natural drug compounds in the drug development process.

Adsorption-induced co-assembly of hairy and isotropic particles

2020 ◽  
Vol 22 (16) ◽  
pp. 8757-8767
Author(s):  
Tomasz Staszewski ◽  
Małgorzata Borówko
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Coarse Grained ◽  
Dynamics Simulations ◽  
Coarse Grained Molecular Dynamics

We use coarse-grained molecular dynamics simulations to study the behavior of polymer-tethered particles immersed in fluids of isotropic particles.

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