scholarly journals Polymer-like model to study the dynamics of dynamin filaments on deformable membrane tubes

2019 ◽  
Author(s):  
Jeffrey K. Noel ◽  
Frank Noé ◽  
Oliver Daumke ◽  
Alexander S. Mikhailov
Keyword(s):  
Thermal Fluctuations ◽  
Membrane Curvature ◽  
Coarse Grained ◽  
Chain Model ◽  
Dependent Manner ◽  
Membrane Tube ◽  
Elastic Filament ◽  
Intrinsic Shape ◽  
Deformable Membrane ◽  
Dynamics Simulations

AbstractPeripheral membrane proteins with intrinsic curvature can act both as sensors of membrane curvature and shape modulators of the underlying membranes. A well-studied example of such proteins is the mechano-chemical GTPase dynamin that assembles into helical filaments around membrane tubes and catalyzes their scission in a GTPase-dependent manner. It is known that the dynamin coat alone, without GTP, can constrict membrane tubes to radii of about 10 nanometers, indicating that the intrinsic shape and elasticity of dynamin filaments should play an important role in membrane remodeling. However, molecular and dynamic understanding of the process is lacking. Here, we develop a dynamical polymer-chain model for a helical elastic filament bound on a deformable membrane tube of conserved mass, accounting for thermal fluctuations in the filament and lipid flows in the membrane. The model is based on a locally-cylindrical helix approximation for dynamin. We obtain the elastic parameters of the dynamin filament by molecular dynamics simulations of its tetrameric building block and also from coarse-grained structure-based simulations of a 17-dimer filament. The results show that the stiffness of dynamin is comparable to that of the membrane. We determine equilibrium shapes of the filament and the membrane, and find that mostly the pitch of the filament, not its radius, is sensitive to variations in membrane tension and stiffness. The close correspondence between experimental estimates of the inner tube radius and those predicted by the model suggests that dynamin’s “stalk” region is responsible for its GTP-independent membrane-shaping ability. The model paves the way for future mesoscopic modeling of dynamin with explicit motor function.

scholarly journals Molecular dynamics simulations of membrane deformation induced by the amphiphilic helices of Epsin, Sar1p and Arf1

2017 ◽  
Author(s):  
Zhen-lu Li
Keyword(s):  
Lipid Membranes ◽  
Critical Role ◽  
Membrane Curvature ◽  
Coarse Grained ◽  
Insertion Depth ◽  
Membrane Deformation ◽  
Specific Distribution ◽  
Amphiphilic Helix ◽  
Coarse Grained Simulations ◽  
Dynamics Simulations

AbstractThe N-terminal amphiphilic helices of proteins Epsin, Sar1p and Arf1 play a critical role in initiating membrane deformation. We present here the study of the interactions of these amphiphilic helices with the lipid membranes by combining the all-atom and coarse-grained simulations. In the all-atom simulations, we find that the amphiphilic helices of Epsin and Sar1p have a shallower insertion depth into the membrane compared to the amphiphilic helix of Arf1, but remarkably, the amphiphilic helices of Epsin and Sar1p induce higher asymmetry in the lipid packing between the two monolayers of the membrane. The insertion depth of amphiphilic helix into the membrane is determined not only by the overall hydrophobicity but also by the specific distribution of polar and non-polar residues along the helix. To directly compare their ability of deforming the membrane, we further apply coarse-grained simulations to investigate the membranes deformation under the insertion of multiple helices. Importantly, it is found that the amphiphilic helices of Epsin and Sar1p generate a larger membrane curvature than that of Arf1, in accord with the experimental results qualitatively. These findings enhance our understanding of the molecular mechanism of the protein-driven membrane remodeling.

scholarly journals Chiral twisting in cytoskeletal polymers regulates filament size and orientation

2018 ◽  
Author(s):  
Handuo Shi ◽  
David Quint ◽  
Ajay Gopinathan ◽  
Kerwyn Casey Huang
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Caulobacter Crescentus ◽  
Membrane Binding ◽  
Membrane Curvature ◽  
Cytoskeletal Proteins ◽  
Coarse Grained ◽  
Biophysical Model ◽  
Dynamics Simulations

AbstractWhile cytoskeletal proteins in the actin family are structurally similar, as filaments they act as critical components of diverse cellular processes across all kingdoms of life. In many rod-shaped bacteria, the actin homolog MreB directs cell-wall insertion and maintains cell shape, but it remains unclear how structural changes to MreB affect its physiological function. To bridge this gap, we performed molecular dynamics simulations forCaulobacter crescentusMreB and then utilized a coarse-grained biophysical model to successfully predict MreB filament propertiesin vivo.We discovered that MreB double protofilaments exhibit left-handed twisting that is dependent on the bound nucleotide and membrane binding; the degree of twisting determines the limit length and orientation of MreB filamentsin vivo.Membrane binding of MreB also induces a stable membrane curvature that is physiologically relevant. Together, our data empower the prediction of cytoskeletal filament size from molecular dynamics simulations, providing a paradigm for connecting protein filament structure and mechanics to cellular functions.

scholarly journals Mechanistic basis for motor-driven membrane constriction by dynamin

2020 ◽  
Author(s):  
Oleg Ganichkin ◽  
Renee Vancraenenbroeck ◽  
Gabriel Rosenblum ◽  
Hagen Hofmann ◽  
Alexander S. Mikhailov ◽  
...  
Keyword(s):  
Single Molecule ◽  
Structural Model ◽  
Molecular Motor ◽  
Coarse Grained ◽  
Gtp Hydrolysis ◽  
Single Molecule Fret ◽  
Membrane Tube ◽  
Mechanistic Basis ◽  
Dynamics Simulations ◽  
Gtpase Cycle

AbstractThe mechano-chemical GTPase dynamin assembles on membrane necks of clathrin-coated vesicles into helical oligomers that constrict and eventually cleave the necks in a GTP-dependent way. It remains not clear whether dynamin achieves this via molecular motor activity and, if so, by what mechanism. Here, we used ensemble kinetics, single-molecule FRET and molecular dynamics simulations to characterize dynamin’s GTPase cycle and determine the powerstroke strength. The results were incorporated into a coarse-grained structural model of dynamin filaments on realistic membrane templates. Working asynchronously, dynamin’s motor modules were found to collectively constrict a membrane tube. Force is generated by motor dimers linking adjacent helical turns and constriction is accelerated by their strain-dependent dissociation. Consistent with experiments, less than a second is needed to constrict a membrane tube to the hemi-fission radius. Thus, a membrane remodeling mechanism relying on cooperation of molecular ratchet motors driven by GTP hydrolysis has been revealed.

scholarly journals Curvature induction and sensing of the F-BAR protein Pacsin1 on lipid membranes via molecular dynamics simulations

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Md. Iqbal Mahmood ◽  
Hiroshi Noguchi ◽  
Kei-ichi Okazaki
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Lipid Membranes ◽  
Lipid Membrane ◽  
Complex Structure ◽  
Membrane Curvature ◽  
Coarse Grained ◽  
Lateral Interaction ◽  
Bar Domain ◽  
Dynamics Simulations

Abstract F-Bin/Amphiphysin/Rvs (F-BAR) domain proteins play essential roles in biological processes that involve membrane remodelling, such as endocytosis and exocytosis. It has been shown that such proteins transform the lipid membrane into tubes. Notably, Pacsin1 from the Pacsin/Syndapin subfamily has the ability to transform the membrane into various morphologies: striated tubes, featureless wide and thin tubes, and pearling vesicles. The molecular mechanism of this interesting ability remains elusive. In this study, we performed all-atom (AA) and coarse-grained (CG) molecular dynamics simulations to investigate the curvature induction and sensing mechanisms of Pacsin1 on a membrane. From AA simulations, we show that Pacsin1 has internal structural flexibility. In CG simulations with parameters tuned from the AA simulations, spontaneous assembly of two Pacsin1 dimers through lateral interaction is observed. Based on the complex structure, we show that the regularly assembled Pacsin1 dimers bend a tensionless membrane. We also show that a single Pacsin1 dimer senses the membrane curvature, binding to a buckled membrane with a preferred curvature. These results provide molecular insights into polymorphic membrane remodelling.

scholarly journals Coarse-Grained Modeling and Molecular Dynamics Simulations of Ca2+-Calmodulin

2021 ◽  
Vol 8 ◽  
Author(s):  
Jules Nde ◽  
Pengzhi Zhang ◽  
Jacob C. Ezerski ◽  
Wei Lu ◽  
Kaitlin Knapp ◽  
...  
Keyword(s):  
Force Field ◽  
Calcium Binding ◽  
Structural Changes ◽  
Tight Binding ◽  
Coarse Grained ◽  
Reciprocal Relation ◽  
Dependent Manner ◽  
Coarse Grained Model ◽  
Target Binding ◽  
Dynamics Simulations

Calmodulin (CaM) is a calcium-binding protein that transduces signals to downstream proteins through target binding upon calcium binding in a time-dependent manner. Understanding the target binding process that tunes CaM’s affinity for the calcium ions (Ca2+), or vice versa, may provide insight into how Ca2+-CaM selects its target binding proteins. However, modeling of Ca2+-CaM in molecular simulations is challenging because of the gross structural changes in its central linker regions while the two lobes are relatively rigid due to tight binding of the Ca2+ to the calcium-binding loops where the loop forms a pentagonal bipyramidal coordination geometry with Ca2+. This feature that underlies the reciprocal relation between Ca2+ binding and target binding of CaM, however, has yet to be considered in the structural modeling. Here, we presented a coarse-grained model based on the Associative memory, Water mediated, Structure, and Energy Model (AWSEM) protein force field, to investigate the salient features of CaM. Particularly, we optimized the force field of CaM and that of Ca2+ ions by using its coordination chemistry in the calcium-binding loops to match with experimental observations. We presented a “community model” of CaM that is capable of sampling various conformations of CaM, incorporating various calcium-binding states, and carrying the memory of binding with various targets, which sets the foundation of the reciprocal relation of target binding and Ca2+ binding in future studies.

scholarly journals Cholesterol Induces Uneven Curvature of Asymmetric Lipid Bilayers

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
S. O. Yesylevskyy ◽  
A. P. Demchenko ◽  
S. Kraszewski ◽  
C. Ramseyer
Keyword(s):  
Molecular Dynamics ◽  
Aspect Ratio ◽  
Lipid Bilayers ◽  
Membrane Curvature ◽  
Coarse Grained ◽  
Large Aspect Ratio ◽  
Curved Structures ◽  
Self Consistent ◽  
Dynamics Simulations

A remarkable flexibility is observed in biological membranes, which allows them to form the structures of different curvatures. We addressed the question of intrinsic ability of phospholipid membranes to form highly curved structures and the role of cholesterol in this process. The distribution of cholesterol in the highly curved asymmetric DOPC/DOPS lipid bilayer was investigated by the coarse-grained molecular dynamics simulations in the membrane patches with large aspect ratio. It is shown that cholesterol induces uneven membrane curvature promoting the formation of extended flattened regions of the membrane interleaved by sharp bends. It is shown that the affinity of cholesterol to anionic DOPS or neutral DOPC lipids is curvature dependent. The cholesterol prefers DOPS to DOPC in either planar or highly curved parts of the membrane. In contrast, in the narrow interval of moderate membrane curvatures this preference is inverted. Our data suggest that there is a complex self-consistent interplay between the membrane curvature and cholesterol distribution in the asymmetric lipid bilayers. The suggested new function of cholesterol may have a biological relevance.

scholarly journals Curvature–undulation coupling as a basis for curvature sensing and generation in bilayer membranes

2016 ◽  
Vol 113 (35) ◽  
pp. E5117-E5124 ◽  
Author(s):  
Ryan P. Bradley ◽  
Ravi Radhakrishnan
Keyword(s):  
Objective Function ◽  
Protein Localization ◽  
Membrane Curvature ◽  
Coarse Grained ◽  
Spontaneous Curvature ◽  
Curvature Sensing ◽  
Cooperative Process ◽  
Dynamics Simulations ◽  
A Site ◽  
Dilute Limit

We present coarse-grained molecular dynamics simulations of the epsin N-terminal homology domain interacting with a lipid bilayer and demonstrate a rigorous theoretical formalism and analysis method for computing the induced curvature field in varying concentrations of the protein in the dilute limit. Our theory is based on the description of the height–height undulation spectrum in the presence of a curvature field. We formulated an objective function to compare the acquired undulation spectrum from the simulations to that of the theory. We recover the curvature field parameters by minimizing the objective function even in the limit where the protein-induced membrane curvature is of the same order as the amplitude due to thermal undulations. The coupling between curvature and undulations leads to significant predictions: (i) Under dilute conditions, the proteins can sense a site of spontaneous curvature at distances much larger than their size; (ii) as the density of proteins increases the coupling focuses and stabilizes the curvature field to the site of the proteins; and (iii) the mapping of the protein localization and the induction of a stable curvature is a cooperative process that can be described through a Hill function.

Extensional Response and Equilibrium Kinetics of Torsionally Relaxed dsDNA Under Tension: A Brownian Dynamics Study

2016 ◽  
Vol 12 (3) ◽  
Author(s):  
Ikenna D. Ivenso
Keyword(s):  
Single Molecule ◽  
Brownian Dynamics ◽  
Thermal Fluctuations ◽  
Aqueous Environment ◽  
Chain Model ◽  
Full Extension ◽  
Applied Tension ◽  
Dynamics Simulations ◽  
Kinetics Of ◽  
Insight Into

Deoxyribonucleic acid (DNA) is a long flexible polyelectrolyte that is housed in the aqueous environment within the cell of an organism. When a length of torsionally relaxed (untwisted) DNA is held in tension, such as is the case in many single molecule experiments, the thermal fluctuations arising from the constant bombardment of the DNA by the surrounding fluid molecules induce bending in it, while the applied tension tends to keep it extended. The combined effect of these influences is that DNA is never at its full extension but eventually attains an equilibrium value of end-to-end extension under these influences. An analytical model was developed to estimate the tension-dependent value of this extension. This model, however, does not provide any insight into the dynamics of the extensional response of DNA to applied tension nor the kinetics of DNA at equilibrium under said tension. This paper reports the results of Brownian dynamics simulations using a discrete wormlike-chain model of DNA that provide some insight into these dynamics and kinetics.

scholarly journals How curvature-generating proteins build scaffolds on membrane nanotubes

2016 ◽  
Vol 113 (40) ◽  
pp. 11226-11231 ◽  
Author(s):  
Mijo Simunovic ◽  
Emma Evergren ◽  
Ivan Golushko ◽  
Coline Prévost ◽  
Henri-François Renard ◽  
...  
Keyword(s):  
Lipid Membranes ◽  
Coarse Grained ◽  
Molecular Scaffolds ◽  
Bar Domain ◽  
Membrane Tube ◽  
Bar Domain Proteins ◽  
Specific Localization ◽  
A Cell ◽  
Dynamics Simulations ◽  
Cooperative Assembly

Bin/Amphiphysin/Rvs (BAR) domain proteins control the curvature of lipid membranes in endocytosis, trafficking, cell motility, the formation of complex subcellular structures, and many other cellular phenomena. They form 3D assemblies that act as molecular scaffolds to reshape the membrane and alter its mechanical properties. It is unknown, however, how a protein scaffold forms and how BAR domains interact in these assemblies at protein densities relevant for a cell. In this work, we use various experimental, theoretical, and simulation approaches to explore how BAR proteins organize to form a scaffold on a membrane nanotube. By combining quantitative microscopy with analytical modeling, we demonstrate that a highly curving BAR protein endophilin nucleates its scaffolds at the ends of a membrane tube, contrary to a weaker curving protein centaurin, which binds evenly along the tube’s length. Our work implies that the nature of local protein–membrane interactions can affect the specific localization of proteins on membrane-remodeling sites. Furthermore, we show that amphipathic helices are dispensable in forming protein scaffolds. Finally, we explore a possible molecular structure of a BAR-domain scaffold using coarse-grained molecular dynamics simulations. Together with fluorescence microscopy, the simulations show that proteins need only to cover 30–40% of a tube’s surface to form a rigid assembly. Our work provides mechanical and structural insights into the way BAR proteins may sculpt the membrane as a high-order cooperative assembly in important biological 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>

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