scholarly journals A Model of the Open Pore MscL Based on Experimental Data and Restrained Coarse Grained Simulations

2012 ◽  
Vol 102 (3) ◽  
pp. 121a-122a
Author(s):  
Evelyne Deplazes ◽  
Dylan Jayatilaka ◽  
Martti Louhivuori ◽  
Siewert-Jan Marrink ◽  
Ben Corry
Keyword(s):  
Experimental Data ◽  
Coarse Grained ◽  
Coarse Grained Simulations

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

2017 ◽  
Author(s):  
Lam T. Nguyen ◽  
Matthew T. Swulius ◽  
Samya Aich ◽  
Mithilesh Mishra ◽  
Grant J. Jensen
Keyword(s):  
Experimental Data ◽  
Cell Division ◽  
Fluorescence Microscopy ◽  
Actin Filaments ◽  
Coarse Grained ◽  
Eukaryotic Cells ◽  
Ring Assembly ◽  
Assembly Result ◽  
Coarse Grained Simulations ◽  
Electron Cryotomography

AbstractCytokinesis in most 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 existing literature and new 3D molecular details from electron cryotomography, here we develop 3D coarse-grained models of actin filaments, unipolar and bipolar myosins, actin crosslinkers, and membranes and simulate their nteractions. Exploring a matrix of possible actomyosin configurations suggested that node-based architectures ike those presently described for ring assembly result in membrane puckers not seen in EM 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.Significance StatementIn most eukaryotes, a ring of actin and myosin drives cell division, but how the elements of the ring are arranged and constrict remain unclear. Here we use 3D coarse-grained simulations to explore various possibilities. Our simulations suggest that if actomyosin is arranged in nodes (as suggested by a popular model of ring assembly), the membrane distorts in ways not seen experimentally. Instead, actin and myosin are more ikely uniformly distributed around the ring. In the model that best fits experimental data, ring tension is generated by interactions between bipolar myosins and actin, and transmitted to the membrane via unipolar myosins. Technologically the study highlights how coarse-grained simulations can test specific mechanistic hypotheses by comparing their predicted outcomes to experimental results.

scholarly journals A multiscale computational study of the conformation of the full-length intrinsically disordered protein MeCP2

2021 ◽  
Author(s):  
Cecilia Chavez-Garcia ◽  
Jerome Henin ◽  
Mikko Karttunen
Keyword(s):  
Experimental Data ◽  
Computational Study ◽  
Intrinsically Disordered Protein ◽  
Full Length ◽  
Conformational Space ◽  
Coarse Grained ◽  
Conformational Ensemble ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Coarse Grained Simulations

The malfunction of the Methyl CpG binding protein 2 (MeCP2) is associated to the Rett syndrome, one of the most common causes of cognitive impairment in females. MeCP2 is an intrinsically disordered protein (IDP), making its experimental characterization a challenge. There is currently no structure available for the full-length MeCP2 in any of the databases, and only the structure of its MBD domain has been solved. We used this structure to build a full-length model of MeCP2 by completing the rest of the protein via ab initio modelling. Using a combination of all-atom and coarse-grained simulations, we characterized its structure and dynamics as well as the conformational space sampled by the ID and TRD domains in the absence of the rest of the protein. The present work is the first computational study of the full-length protein. Two main conformations were sampled in the coarse-grained simulations: a globular structure similar to the one observed in the all-atom force field and a two-globule conformation. Our all-atom model is in good agreement with the available experimental data, predicting amino acid W104 to be buried, amino acids R111 and R133 to be solvent accessible, and having 4.1% of α-helix content, compared to the 4% found experimentally. Finally, we compared the model predicted by AlphaFold to our Modeller model. The model was not stable in water and underwent further folding. Together, these simulations provide a detailed (if perhaps incomplete) conformational ensemble of the full-length MeCP2, which is compatible with experimental data and can be the basis of further studies, e.g., on mutants of the protein or its interactions with its biological partners.

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 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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