scholarly journals Coarse-grained simulations of bacterial cell wall growth reveal that local coordination alone can be sufficient to maintain rod shape

2015 ◽  
Vol 112 (28) ◽  
pp. E3689-E3698 ◽  
Author(s):  
Lam T. Nguyen ◽  
James C. Gumbart ◽  
Morgan Beeby ◽  
Grant J. Jensen
Keyword(s):  
Cell Wall ◽  
Failure Modes ◽  
Current Theory ◽  
Glycoside Hydrolases ◽  
Coarse Grained ◽  
Cell Integrity ◽  
Local Coordination ◽  
New Material ◽  
Coarse Grained Simulations ◽  
The Individual

Bacteria are surrounded by a peptidoglycan (PG) cell wall that must be remodeled to allow cell growth. While many structural details and properties of PG and the individual enzymes involved are known, how the process is coordinated to maintain cell integrity and rod shape is not understood. We have developed a coarse-grained method to simulate how individual transglycosylases, transpeptidases, and endopeptidases could introduce new material into an existing unilayer PG network. We find that a simple model with no enzyme coordination fails to maintain cell wall integrity and rod shape. We then iteratively analyze failure modes and explore different mechanistic hypotheses about how each problem might be overcome by the macromolecules involved. In contrast to a current theory, which posits that long MreB filaments are needed to coordinate PG insertion sites, we find that local coordination of enzyme activities in individual complexes can be sufficient to maintain cell integrity and rod shape. We also present possible molecular explanations for the existence of monofunctional transpeptidases and glycosidases (glycoside hydrolases), trimeric peptide crosslinks, cell twisting during growth, and synthesis of new strands in pairs.

scholarly journals Coarse-grained simulations of actomyosin rings point to a nodeless model involving both unipolar and bipolar myosins

2018 ◽  
Vol 29 (11) ◽  
pp. 1318-1331 ◽  
Author(s):  
Lam T. Nguyen ◽  
Matthew T. Swulius ◽  
Samya Aich ◽  
Mithilesh Mishra ◽  
Grant J. Jensen
Keyword(s):  
Cell Wall ◽  
Actin Filaments ◽  
Three Dimensional ◽  
Coarse Grained ◽  
Eukaryotic Cells ◽  
Ring Assembly ◽  
Assembly Result ◽  
Microscope Images ◽  
Coarse Grained Simulations ◽  
Electron Cryotomography

Cytokinesis in many eukaryotic cells is orchestrated by a contractile actomyosin ring. While many of the proteins involved are known, the mechanism of constriction remains unclear. Informed by the existing literature and new three-dimensional (3D) molecular details from electron cryotomography, here we develop 3D coarse-grained models of actin filaments, unipolar and bipolar myosins, actin cross-linkers, and membranes and simulate their interactions. Assuming that local force on the membrane results in inward growth of the cell wall, we explored a matrix of possible actomyosin configurations and found that node-based architectures like those presently described for ring assembly result in membrane puckers not seen in electron microscope images of real cells. Instead, the model that best matches data from fluorescence microscopy, electron cryotomography, and biochemical experiments is one in which actin filaments transmit force to the membrane through evenly distributed, membrane-attached, unipolar myosins, with bipolar myosins in the ring driving contraction. While at this point this model is only favored (not proven), the work highlights the power of coarse-grained biophysical simulations to compare complex mechanistic hypotheses.

Grand-Reaction Method for Simulations of Ionization Equilibria and Ion Partitioning in a Broad Range of pH and Ionic Strength

2019 ◽  
Author(s):  
Jonas Landsgesell ◽  
Oleg Rud ◽  
Pascal Hebbeker ◽  
Raju Lunkad ◽  
Peter Košovan ◽  
...  
Keyword(s):  
Mean Field ◽  
Coarse Grained ◽  
Reactive System ◽  
Acid Base ◽  
Buffer Solution ◽  
Reaction Method ◽  
Ionization Equilibria ◽  
Coarse Grained Simulations ◽  
Ph Range ◽  
Weak Polyelectrolytes

We introduce the grand-reaction method for coarse-grained simulations of acid-base equilibria in a system coupled to a reservoir at a given pH and concentration of added salt. It can be viewed as an extension of the constant-pH method and the reaction ensemble, combining explicit simulations of reactions within the system, and grand-canonical exchange of particles with the reservoir. Unlike the previously introduced methods, the grand-reaction method is applicable to acid-base equilibria in the whole pH range because it avoids known artifacts. However, the method is more general, and can be used for simulations of any reactive system coupled to a reservoir of a known composition. To demonstrate the advantages of the grand-reaction method, we simulated a model system: A solution of weak polyelectrolytes in equilibrium with a buffer solution. By carefully accounting for the exchange of all constituents, the method ensures that all chemical potentials are equal in the system and in the multi-component reservoir. Thus, the grand-reaction method is able to predict non-monotonic swelling of weak polyelectrolytes as a function of pH, that has been known from mean-field predictions and from experiments but has never been observed in coarse-grained simulations. Finally, we outline possible extensions and further generalizations of the method, and provide a set of guidelines to enable safe usage of the method by a broad community of users.<br><br>

scholarly journals Receptor Internalization in Yeast Requires the Tor2-Rho1 Signaling Pathway

2003 ◽  
Vol 14 (11) ◽  
pp. 4676-4684 ◽  
Author(s):  
Amy K.A. deHart ◽  
Joshua D. Schnell ◽  
Damian A. Allen ◽  
Ju-Yun Tsai ◽  
Linda Hicke
Keyword(s):  
Cell Wall ◽  
Cell Cycle Progression ◽  
Structural Integrity ◽  
Nutrient Sensing ◽  
Receptor Internalization ◽  
Cell Integrity ◽  
Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Similar Phenotype ◽  
Cell Growth And Differentiation

Efficient internalization of proteins from the cell surface is essential for regulating cell growth and differentiation. In a screen for yeast mutants defective in ligand-stimulated internalization of the α-factor receptor, we identified a mutant allele of TOR2, tor2G2128R. Tor proteins are known to function in translation initiation and nutrient sensing and are required for cell cycle progression through G1. Yeast Tor2 has an additional role in regulating the integrity of the cell wall by activating the Rho1 guanine nucleotide exchange factor Rom2. The endocytic defect in tor2G2128Rcells is due to disruption of this Tor2 unique function. Other proteins important for cell integrity, Rom2 and the cell integrity sensor Wsc1, are also required for efficient endocytosis. A rho1 mutant specifically defective in activation of the glucan synthase Fks1/2 does not internalize α-factor efficiently, and fks1Δ cells exhibit a similar phenotype. Removal of the cell wall does not inhibit internalization, suggesting that the function of Rho1 and Fks1 in endocytosis is not through cell wall synthesis or structural integrity. These findings reveal a novel function for the Tor2-Rho1 pathway in controlling endocytosis in yeast, a function that is mediated in part through the plasma membrane protein Fks1.

scholarly journals Prediction and validation of protein intermediate states from structurally rich ensembles and coarse-grained simulations

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Laura Orellana ◽  
Ozge Yoluk ◽  
Oliver Carrillo ◽  
Modesto Orozco ◽  
Erik Lindahl
Keyword(s):  
Coarse Grained ◽  
Intermediate States ◽  
Coarse Grained Simulations

Effect of oligonucleic acid (ONA) backbone features on assembly of ONA–star polymer conjugates: a coarse-grained molecular simulation study

Soft Matter ◽  
2017 ◽  
Vol 13 (38) ◽  
pp. 6770-6783 ◽  
Author(s):  
Joshua E. Condon ◽  
Arthi Jayaraman
Keyword(s):  
Molecular Simulation ◽  
Simulation Study ◽  
Coarse Grained ◽  
Star Polymer ◽  
Backbone Flexibility ◽  
Polymer Architecture ◽  
Polymer Conjugates ◽  
Coarse Grained Simulations

Using coarse-grained simulations, we study the effect of varying oligonucleic acid (ONA) backbone flexibility, ONA charge and star polymer architecture on structure and thermodynamics of ONA–star polymer conjugates assembly.

scholarly journals Coarse-grained Simulations and AFM Nanoindentation Experiments on a Hepatitis B Virus Capsid

2009 ◽  
Vol 96 (3) ◽  
pp. 423a
Author(s):  
Anton S. Arkhipov ◽  
Wouter Roos ◽  
Gijs Wuite ◽  
Klaus Schulten
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Coarse Grained ◽  
Virus Capsid ◽  
B Virus ◽  
Coarse Grained Simulations
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