scholarly journals Coarse-grained simulation reveals key features of HIV-1 capsid self-assembly

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
John M. A. Grime ◽  
James F. Dama ◽  
Barbie K. Ganser-Pornillos ◽  
Cora L. Woodward ◽  
Grant J. Jensen ◽  
...  
Keyword(s):  
Self Assembly ◽  
Coarse Grained ◽  
Key Features ◽  
Hiv 1

scholarly journals Coarse-grained simulation reveals key features of HIV-1 capsid self-assembly

2016 ◽  
Author(s):  
John M A Grime ◽  
James F Dama ◽  
Barbie K Ganser-Pornillos ◽  
Cora L Woodward ◽  
Grant J Jensen ◽  
...  
Keyword(s):  
Self Assembly ◽  
Coarse Grained ◽  
Capsid Assembly ◽  
Molecular Crowding ◽  
Local Conditions ◽  
Conformational Variability ◽  
Multi Stage ◽  
Capsid Shell ◽  
Coarse Grained Simulations ◽  
Hiv 1

The maturation of HIV-1 viral particles is essential for viral infectivity. During maturation, many copies of the capsid protein (CA) self-assemble into a capsid shell to enclose the viral RNA. The mechanistic details of the initiation and early stages of capsid assembly remain to be delineated. We present coarse-grained simulations of capsid assembly under various conditions, considering not only capsid lattice self-assembly but also the potential disassembly of capsid upon delivery to the cytoplasm of a target cell. The effects of CA concentration, molecular crowding, and the conformational variability of CA are described, with results indicating that capsid nucleation and growth is a multi-stage process requiring well-defined metastable intermediates. Generation of the mature capsid lattice is sensitive to local conditions, with relatively subtle changes in CA concentration and molecular crowding influencing self-assembly and the ensemble of structural morphologies.

scholarly journals Immature HIV-1 lattice assembly dynamics are regulated by scaffolding from nucleic acid and the plasma membrane

2017 ◽  
Vol 114 (47) ◽  
pp. E10056-E10065 ◽  
Author(s):  
Alexander J. Pak ◽  
John M. A. Grime ◽  
Prabuddha Sengupta ◽  
Antony K. Chen ◽  
Aleksander E. P. Durumeric ◽  
...  
Keyword(s):  
Self Assembly ◽  
Structural Data ◽  
Single Particle Tracking ◽  
Viral Rna ◽  
Coarse Grained ◽  
Amino Terminal ◽  
Gag Polyprotein ◽  
Amino Terminal Domain ◽  
Hiv 1 ◽  
Simple Network

The packaging and budding of Gag polyprotein and viral RNA is a critical step in the HIV-1 life cycle. High-resolution structures of the Gag polyprotein have revealed that the capsid (CA) and spacer peptide 1 (SP1) domains contain important interfaces for Gag self-assembly. However, the molecular details of the multimerization process, especially in the presence of RNA and the cell membrane, have remained unclear. In this work, we investigate the mechanisms that work in concert between the polyproteins, RNA, and membrane to promote immature lattice growth. We develop a coarse-grained (CG) computational model that is derived from subnanometer resolution structural data. Our simulations recapitulate contiguous and hexameric lattice assembly driven only by weak anisotropic attractions at the helical CA–SP1 junction. Importantly, analysis from CG and single-particle tracking photoactivated localization (spt-PALM) trajectories indicates that viral RNA and the membrane are critical constituents that actively promote Gag multimerization through scaffolding, while overexpression of short competitor RNA can suppress assembly. We also find that the CA amino-terminal domain imparts intrinsic curvature to the Gag lattice. As a consequence, immature lattice growth appears to be coupled to the dynamics of spontaneous membrane deformation. Our findings elucidate a simple network of interactions that regulate the early stages of HIV-1 assembly and budding.

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.

Coarse-grained simulation of the self-assembly of lipid vesicles concomitantly with novel block copolymers with multiple tails

Soft Matter ◽  
2021 ◽  
Author(s):  
Alexander Kantardjiev
Keyword(s):  
Molecular Dynamics ◽  
Block Copolymers ◽  
Self Assembly ◽  
Lipid Vesicles ◽  
The Self ◽  
Coarse Grained ◽  
Copolymer Concentration ◽  
Copolymer Structure ◽  
Coarse Grained Molecular Dynamics

We carried out a series of coarse-grained molecular dynamics liposome-copolymer simulations with varying extent of copolymer concentration in an attempt to understand the effect of copolymer structure and concentration on vesicle self-assembly and stability.

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...

Drying-Mediated Hierarchical Self-Assembly of Nanoparticles:  A Dynamical Coarse-Grained Approach

2008 ◽  
Vol 112 (12) ◽  
pp. 4498-4506 ◽  
Author(s):  
Orly Kletenik-Edelman ◽  
Elina Ploshnik ◽  
Asaf Salant ◽  
Roy Shenhar ◽  
Uri Banin ◽  
...  
Keyword(s):  
Self Assembly ◽  
Coarse Grained

scholarly journals Immature HIV-1 Lattice Assembly Dynamics are Regulated by Scaffolding from Nucleic Acid and the Plasma Membrane

2017 ◽  
Author(s):  
Alexander J. Pak ◽  
John M. A. Grime ◽  
Prabuddha Sengupta ◽  
Antony K. Chen ◽  
Aleksander E. P. Durumeric ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Nucleic Acid ◽  
Structural Data ◽  
Single Particle Tracking ◽  
Coarse Grained ◽  
Intermediate Step ◽  
Amino Terminal ◽  
Gag Polyprotein ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACTThe packaging and budding of Gag polyprotein and viral ribonucleic acid (RNA) is a critical step in the human immunodeficiency virus-1 (HIV-1) lifecycle. High-resolution structures of the Gag polyprotein have revealed that the capsid (CA) and spacer peptide 1 (SP1) domains contain important interfaces for Gag self-assembly. However, the molecular details of the multimerization process, especially in the presence of RNA and the cell membrane, have remained unclear. In this work, we investigate the mechanisms that work in concert between the polyproteins, RNA, and membrane to promote immature lattice growth. We develop a coarse-grained (CG) computational model that is derived from sub-nanometer resolution structural data. Our simulations recapitulate contiguous and hexameric lattice assembly driven only by weak anisotropic attractions at the helical CA-SP1 junction. Importantly, analysis from CG and single-particle tracking photoactivated localization (spt-PALM) trajectories indicates that viral RNA and the membrane are critical constituents that actively promote Gag multimerization through scaffolding, while over-expression of short competitor RNA can suppress assembly. We also find that the CA amino-terminal domain imparts intrinsic curvature to the Gag lattice. As a consequence, immature lattice growth appears to be coupled to the dynamics of spontaneous membrane deformation. Our findings elucidate a simple network of interactions that regulate the early stages of HIV-1 assembly and budding.SIGNIFICANCE STATEMENTIn order for human immunodeficiency virus to proliferate, viral proteins and genomic dimers are assembled at host cell membranes and released as immature virions. Disrupting this key intermediate step in viral replication is a potential target for treatment. However, a detailed molecular view of this process remains lacking. Here, we elucidate a network of constitutive interactions that regulate viral assembly dynamics through a combined computational and experimental approach. Specifically, our analysis reveals the active roles of nucleic acid and the membrane as scaffolds that promote the multimerization of Gag polyprotein which proceeds through multi-step and self-correcting nucleation. Our findings also illustrate the functional importance of the N-terminal, C-terminal, and spacer peptide 1 protein domains.

scholarly journals Controlling the length of porphyrin supramolecular polymers via coupled equilibria and dilution-induced supramolecular polymerization

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Elisabeth Weyandt ◽  
Luigi Leanza ◽  
Riccardo Capelli ◽  
Giovanni M. Pavan ◽  
Ghislaine Vantomme ◽  
...  
Keyword(s):  
Complex Systems ◽  
Self Assembly ◽  
Chiral Discrimination ◽  
Coarse Grained ◽  
Supramolecular Polymers ◽  
Supramolecular System ◽  
Precise Control ◽  
Aggregate Morphology ◽  
The Individual ◽  
Supramolecular Polymerization

AbstractMulti-component systems often display convoluted behavior, pathway complexity and coupled equilibria. In recent years, several ways to control complex systems by manipulating the subtle balances of interaction energies between the individual components have been explored and thereby shifting the equilibrium between different aggregate states. Here we show the enantioselective chain-capping and dilution-induced supramolecular polymerization with a Zn2+-porphyrin-based supramolecular system when going from long, highly cooperative supramolecular polymers to short, disordered aggregates by adding a monotopic Mn3+-porphyrin monomer. When mixing the zinc and manganese centered monomers, the Mn3+-porphyrins act as chain-cappers for Zn2+-porphyrin supramolecular polymers, effectively hindering growth of the copolymer and reducing the length. Upon dilution, the interaction between chain-capper and monomers weakens as the equilibria shift and long supramolecular polymers form again. This dynamic modulation of aggregate morphology and length is achieved through enantioselectivity in the aggregation pathways and concentration-sensitive equilibria. All-atom and coarse-grained molecular simulations provide further insights into the mixing of the species and their exchange dynamics. Our combined experimental and theoretical approach allows for precise control of molecular self-assembly and chiral discrimination in complex systems.

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