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.

Effective interaction between small unilamellar vesicles as probed by coarse-grained molecular dynamics simulations

2014 ◽  
Vol 86 (2) ◽  
pp. 215-222 ◽  
Author(s):  
Wataru Shinoda ◽  
Michael L. Klein
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Effective Interaction ◽  
Md Simulations ◽  
Coarse Grained ◽  
Repulsive Interaction ◽  
Spontaneous Curvature ◽  
Unilamellar Vesicles ◽  
Small Unilamellar Vesicles ◽  
Dynamics Simulations

Abstract A series of molecular dynamics (MD) simulations has been undertaken to investigate the effective interaction between vesicles including PC (phosphatidylcholine) and PE (phosphatidylethanolamine) lipids using the Shinoda–DeVane–Klein coarse-grained force field. No signatures of fusion were detected during MD simulations employing two apposed unilamellar vesicles, each composed of 1512 lipid molecules. Association free energy of the two stable vesicles depends on the lipid composition. The two PC vesicles exhibit a purely repulsive interaction with each other, whereas two PE vesicles show a free energy gain at the contact. A mixed PC/PE (1:1) vesicle shows a higher flexibility having a lower energy barrier on the deformation, which is caused by lipid sorting within each leaflet of the membranes. With a preformed channel or stalk between proximal membranes, PE molecules contribute to stabilize the stalk. The results suggest that the lipid components forming the membrane with a negative spontaneous curvature contribute to stabilize the stalk between two vesicles in contact.

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 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 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.

Vesicle deformation and division induced by flip-flop of lipid molecules

Soft Matter ◽  
2021 ◽  
Author(s):  
Naohito Urakami ◽  
Yuka Sakuma ◽  
Toshikaze Chiba ◽  
Masayuki Imai
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Single Component ◽  
Coarse Grained ◽  
Spontaneous Curvature ◽  
Unilamellar Vesicles ◽  
Flip Flop ◽  
Small Unilamellar Vesicles ◽  
Dynamics Simulations ◽  
Coarse Grained Molecular Dynamics

We investigated the deformation of small unilamellar vesicles (SUVs) induced by flip-flops of lipids using coarse-grained molecular dynamics simulations. In case of single-component SUVs composed of zero spontaneous curvature lipids...

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 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 Structure and dynamics of the SARS-CoV-2 envelope protein monomer

2021 ◽  
Author(s):  
Alexander Kuzmin ◽  
Philipp Orekhov ◽  
Roman Astashkin ◽  
Valentin Gordeliy ◽  
Ivan Gushchin
Keyword(s):  
Envelope Protein ◽  
Transmembrane Domain ◽  
Membrane Surface ◽  
Protein A ◽  
Membrane Curvature ◽  
Curvature Sensing ◽  
Structure And Dynamics ◽  
E Protein ◽  
Viral Particles ◽  
Dynamics Simulations

AbstractCoronaviruses, especially SARS-CoV-2, present an ongoing threat for human wellbeing. Consequently, elucidation of molecular determinants of their function and interaction with host is an important task. Whereas some of the coronaviral proteins are extensively characterized, others remain understudied. Here, we use molecular dynamics simulations to analyze the structure and dynamics of the SARS-CoV-2 envelope protein (E protein, a viroporin) in the monomeric form. The protein consists of three parts: hydrophobic α-helical transmembrane domain (TMD) and amphiphilic α-helices H2 and H3, which are connected by flexible linkers. We show that TMD is tilted in the membrane, with phenylalanines Phe20, Phe23 and Phe26 facing the lumen. H2 and H3 reside at the membrane surface. Orientation of H2 is not affected by glycosylation, but strongly influenced by palmitoylation pattern of cysteines Cys40, Cys43 and Cys44. On the other hand, glycosylation affects the orientation of H3 and prevents its stacking with H2. We also find that the E protein both generates and senses the membrane curvature, preferably localizing with the cytoplasmic part at the convex regions of the membrane. Curvature sensing may be favorable for assembly of the E protein oligomers, whereas induction of curvature may facilitate budding of the viral particles. The presented results may be helpful for better understanding of the function of coronaviral E protein and viroporins in general, and for overcoming the ongoing SARS-CoV-2 pandemic.

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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