scholarly journals Emergence of chromatin hierarchical loops from protein disorder and nucleosome asymmetry

2020 ◽  
Vol 117 (13) ◽  
pp. 7216-7224 ◽  
Author(s):  
Akshay Sridhar ◽  
Stephen E. Farr ◽  
Guillem Portella ◽  
Tamar Schlick ◽  
Modesto Orozco ◽  
...  
Keyword(s):  
Large Scale ◽  
Coarse Grained ◽  
Multiscale Approach ◽  
Protein Disorder ◽  
Wide Range ◽  
Chromatin Structural ◽  
Degree Of Condensation ◽  
Dynamics Simulations ◽  
Nucleosome Binding

Protein flexibility and disorder is emerging as a crucial modulator of chromatin structure. Histone tail disorder enables transient binding of different molecules to the nucleosomes, thereby promoting heterogeneous and dynamic internucleosome interactions and making possible recruitment of a wide-range of regulatory and remodeling proteins. On the basis of extensive multiscale modeling we reveal the importance of linker histone H1 protein disorder for chromatin hierarchical looping. Our multiscale approach bridges microsecond-long bias-exchange metadynamics molecular dynamics simulations of atomistic 211-bp nucleosomes with coarse-grained Monte Carlo simulations of 100-nucleosome systems. We show that the long C-terminal domain (CTD) of H1—a ubiquitous nucleosome-binding protein—remains disordered when bound to the nucleosome. Notably, such CTD disorder leads to an asymmetric and dynamical nucleosome conformation that promotes chromatin structural flexibility and establishes long-range hierarchical loops. Furthermore, the degree of condensation and flexibility of H1 can be fine-tuned, explaining chromosomal differences of interphase versus metaphase states that correspond to partial and hyperphosphorylated H1, respectively. This important role of H1 protein disorder in large-scale chromatin organization has a wide range of biological implications.

Events in Northern Africa and Middle East: Causes and Consequences

2011 ◽  
pp. 11-25
Author(s):  
I. Labinskaya
Keyword(s):  
Middle East ◽  
North Africa ◽  
Large Scale ◽  
Arab Countries ◽  
Northern Africa ◽  
External Factors ◽  
Wide Range ◽  
The Usa ◽  
Oriental Studies

Political developments in North Africa and the Middle East that have begun in January 2011 are gaining strength and involve an increasing number of Arab countries. The participants of the Roundtable – experts from IMEMO, Institute of Oriental Studies (RAS), Institute of the USA and Canada (RAS) and Mrs. E. Suponina from “Moscow News” newspaper analyzed a wide range of issues associated with these events. Among them are: 1) the reasons for such a large-scale explosion, 2) the nature of the discussed developments (revolutions, riots?) and who are the subjects of the current “Arab drama”, 3) the role of Islam and political Islamism, 4) the role of external factors.

scholarly journals The role of airborne volcanic ash for the surface ocean biogeochemical iron-cycle: a review

2009 ◽  
Vol 6 (4) ◽  
pp. 6441-6489 ◽  
Author(s):  
S. Duggen ◽  
N. Olgun ◽  
P. Croot ◽  
L. Hoffmann ◽  
H. Dietze ◽  
...  
Keyword(s):  
Large Scale ◽  
Volcanic Ash ◽  
Volcanic Eruptions ◽  
Research Field ◽  
Ash Deposition ◽  
Future Directions ◽  
Iron Cycle ◽  
Surface Ocean ◽  
Wide Range

Abstract. Iron is a key micronutrient for phytoplankton growth in the surface ocean. Yet the significance of volcanism for the marine biogeochemical iron-cycle is poorly constrained. Recent studies, however, suggest that offshore deposition of airborne ash from volcanic eruptions is a way to inject significant amounts of bio-available iron into the surface ocean. Volcanic ash may be transported up to several tens of kilometres high into the atmosphere during large-scale eruptions and fine ash may encircle the globe for years, thereby reaching even the remotest and most iron-starved oceanic areas. Scientific ocean drilling demonstrates that volcanic ash layers and dispersed ash particles are frequently found in marine sediments and that therefore volcanic ash deposition and iron-injection into the oceans took place throughout much of the Earth's history. The data from geochemical and biological experiments, natural evidence and satellite techniques now available suggest that volcanic ash is a so far underestimated source for iron in the surface ocean, possibly of similar importance as aeolian dust. Here we summarise the development of and the knowledge in this fairly young research field. The paper covers a wide range of chemical and biological issues and we make recommendations for future directions in these areas. The review paper may thus be helpful to improve our understanding of the role of volcanic ash for the marine biogeochemical iron-cycle, marine primary productivity and the ocean-atmosphere exchange of CO2 and other gases relevant for climate throughout the Earth's history.

scholarly journals Modelling lipid systems in fluid with Lattice Boltzmann Molecular Dynamics simulations and hydrodynamics

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Astrid F. Brandner ◽  
Stepan Timr ◽  
Simone Melchionna ◽  
Philippe Derreumaux ◽  
Marc Baaden ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Lattice Boltzmann ◽  
Coarse Grained ◽  
Implicit Solvent ◽  
Mesoscopic Scale ◽  
Coarse Grained Model ◽  
Dynamics Simulations ◽  
Cellular Compartments ◽  
Biological Entities

Abstract In this work we present the coupling between Dry Martini, an efficient implicit solvent coarse-grained model for lipids, and the Lattice Boltzmann Molecular Dynamics (LBMD) simulation technique in order to include naturally hydrodynamic interactions in implicit solvent simulations of lipid systems. After validating the implementation of the model, we explored several systems where the action of a perturbing fluid plays an important role. Namely, we investigated the role of an external shear flow on the dynamics of a vesicle, the dynamics of substrate release under shear, and inquired the dynamics of proteins and substrates confined inside the core of a vesicle. Our methodology enables future exploration of a large variety of biological entities and processes involving lipid systems at the mesoscopic scale where hydrodynamics plays an essential role, e.g. by modulating the migration of proteins in the proximity of membranes, the dynamics of vesicle-based drug delivery systems, or, more generally, the behaviour of proteins in cellular compartments.

scholarly journals Reaction–diffusion basis of retroviral infectivity

2016 ◽  
Vol 374 (2080) ◽  
pp. 20160148 ◽  
Author(s):  
S. Kashif Sadiq
Keyword(s):  
Chemical Reactions ◽  
Membrane Surface ◽  
Reaction Diffusion ◽  
Coarse Graining ◽  
Coarse Grained ◽  
Multiscale Approach ◽  
The Matrix ◽  
Membrane Bound ◽  
Spatio Temporal ◽  
Dynamics Simulations

Retrovirus particle (virion) infectivity requires diffusion and clustering of multiple transmembrane envelope proteins (Env 3 ) on the virion exterior, yet is triggered by protease-dependent degradation of a partially occluding, membrane-bound Gag polyprotein lattice on the virion interior. The physical mechanism underlying such coupling is unclear and only indirectly accessible via experiment. Modelling stands to provide insight but the required spatio-temporal range far exceeds current accessibility by all-atom or even coarse-grained molecular dynamics simulations. Nor do such approaches account for chemical reactions, while conversely, reaction kinetics approaches handle neither diffusion nor clustering. Here, a recently developed multiscale approach is considered that applies an ultra-coarse-graining scheme to treat entire proteins at near-single particle resolution, but which also couples chemical reactions with diffusion and interactions. A model is developed of Env 3 molecules embedded in a truncated Gag lattice composed of membrane-bound matrix proteins linked to capsid subunits, with freely diffusing protease molecules. Simulations suggest that in the presence of Gag but in the absence of lateral lattice-forming interactions, Env 3 diffuses comparably to Gag-absent Env 3 . Initial immobility of Env 3 is conferred through lateral caging by matrix trimers vertically coupled to the underlying hexameric capsid layer. Gag cleavage by protease vertically decouples the matrix and capsid layers, induces both matrix and Env 3 diffusion, and permits Env 3 clustering. Spreading across the entire membrane surface reduces crowding, in turn, enhancing the effect and promoting infectivity. This article is part of the themed issue ‘Multiscale modelling at the physics–chemistry–biology interface’.

scholarly journals The solubility product extends the buffering concept to heterotypic biomolecular condensates.

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Aniruddha Chattaraj ◽  
Michael L Blinov ◽  
Leslie M Loew
Keyword(s):  
Concentration Dependence ◽  
Solubility Product ◽  
Monomer Concentration ◽  
Coarse Grained ◽  
Wide Range ◽  
Particle Simulations ◽  
Large Clusters ◽  
Free Monomer ◽  
Liquid Liquid Phase Separation

Biomolecular condensates are formed by liquid-liquid phase separation (LLPS) of multivalent molecules. LLPS from a single ('homotypic') constituent is governed by buffering: above a threshold, free monomer concentration is clamped, with all added molecules entering the condensed phase. However, both experiment and theory demonstrate that buffering fails for the concentration dependence of multi-component ('heterotypic') LLPS. Using network-free stochastic modeling, we demonstrate that LLPS can be described by the solubility product constant (Ksp): the product of free monomer concentrations, accounting for the ideal stoichiometries governed by the valencies, displays a threshold above which additional monomers are funneled into large clusters; this reduces to simple buffering for homotypic systems. The Ksp regulates the composition of the dilute phase for a wide range of valencies and stoichiometries. The role of Ksp is further supported by coarse-grained spatial particle simulations. Thus, the solubility product offers a general formulation for the concentration dependence of LLPS.

scholarly journals A Multiscale Coarse-grained Model of the SARS-CoV-2 Virion

2020 ◽  
Author(s):  
Alvin Yu ◽  
Alexander J. Pak ◽  
Peng He ◽  
Viviana Monje-Galvan ◽  
Lorenzo Casalino ◽  
...  
Keyword(s):  
Large Scale ◽  
Molecular Model ◽  
Structural Data ◽  
Coarse Grained ◽  
Atomistic Simulations ◽  
Current Status ◽  
Multiscale Approach ◽  
X Ray Crystallography ◽  
Coarse Grained Model ◽  
Viral Particles

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic. Computer simulations of complete viral particles can provide theoretical insights into large-scale viral processes including assembly, budding, egress, entry, and fusion. Detailed atomistic simulations, however, are constrained to shorter timescales and require billion-atom simulations for these processes. Here, we report the current status and on-going development of a largely “bottom-up” coarse-grained (CG) model of the SARS-CoV-2 virion. Structural data from a combination of cryo-electron microscopy (cryo-EM), x-ray crystallography, and computational predictions were used to build molecular models of structural SARS-CoV-2 proteins, which were then assembled into a complete virion model. We describe how CG molecular interactions can be derived from all-atom simulations, how viral behavior difficult to capture in atomistic simulations can be incorporated into the CG models, and how the CG models can be iteratively improved as new data becomes publicly available. Our initial CG model and the detailed methods presented are intended to serve as a resource for researchers working on COVID-19 who are interested in performing multiscale simulations of the SARS-CoV-2 virion.Significance StatementThis study reports the construction of a molecular model for the SARS-CoV-2 virion and details our multiscale approach towards model refinement. The resulting model and methods can be applied to and enable the simulation of SARS-CoV-2 virions.

scholarly journals Classification of protein–protein association rates based on biophysical informatics

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Kalyani Dhusia ◽  
Yinghao Wu
Keyword(s):  
Large Scale ◽  
Cross Validation ◽  
Protein Complexes ◽  
Dynamic Properties ◽  
Conformational Dynamics ◽  
Classification Model ◽  
Coarse Grained ◽  
Modeling Framework ◽  
Validation Data ◽  
Wide Range

Abstract Background Proteins form various complexes to carry out their versatile functions in cells. The dynamic properties of protein complex formation are mainly characterized by the association rates which measures how fast these complexes can be formed. It was experimentally observed that the association rates span an extremely wide range with over ten orders of magnitudes. Identification of association rates within this spectrum for specific protein complexes is therefore essential for us to understand their functional roles. Results To tackle this problem, we integrate physics-based coarse-grained simulations into a neural-network-based classification model to estimate the range of association rates for protein complexes in a large-scale benchmark set. The cross-validation results show that, when an optimal threshold was selected, we can reach the best performance with specificity, precision, sensitivity and overall accuracy all higher than 70%. The quality of our cross-validation data has also been testified by further statistical analysis. Additionally, given an independent testing set, we can successfully predict the group of association rates for eight protein complexes out of ten. Finally, the analysis of failed cases suggests the future implementation of conformational dynamics into simulation can further improve model. Conclusions In summary, this study demonstrated that a new modeling framework that combines biophysical simulations with bioinformatics approaches is able to identify protein–protein interactions with low association rates from those with higher association rates. This method thereby can serve as a useful addition to a collection of existing experimental approaches that measure biomolecular recognition.

scholarly journals Tubulin tails and their modifications regulate protein diffusion on microtubules

2020 ◽  
Vol 117 (16) ◽  
pp. 8876-8883 ◽  
Author(s):  
Lavi S. Bigman ◽  
Yaakov Levy
Keyword(s):  
Molecular Mechanism ◽  
Electrostatic Interactions ◽  
Intrinsically Disordered Protein ◽  
Coarse Grained ◽  
Protein Diffusion ◽  
Intrinsically Disordered ◽  
Essential Components ◽  
Regulate Protein ◽  
Dynamics Simulations

Microtubules (MTs) are essential components of the eukaryotic cytoskeleton that serve as “highways” for intracellular trafficking. In addition to the well-known active transport of cargo by motor proteins, many MT-binding proteins seem to adopt diffusional motility as a transportation mechanism. However, because of the limited spatial resolution of current experimental techniques, the detailed mechanism of protein diffusion has not been elucidated. In particular, the precise role of tubulin tails and tail modifications in the diffusion process is unclear. Here, using coarse-grained molecular dynamics simulations validated against atomistic simulations, we explore the molecular mechanism of protein diffusion along MTs. We found that electrostatic interactions play a central role in protein diffusion; the disordered tubulin tails enhance affinity but slow down diffusion, and diffusion occurs in discrete steps. While diffusion along wild-type MT is performed in steps of dimeric tubulin, the removal of the tails results in a step of monomeric tubulin. We found that the energy barrier for diffusion is larger when diffusion on MTs is mediated primarily by the MT tails rather than the MT body. In addition, globular proteins (EB1 and PRC1) diffuse more slowly than an intrinsically disordered protein (Tau) on MTs. Finally, we found that polyglutamylation and polyglycylation of tubulin tails lead to slower protein diffusion along MTs, although polyglycylation leads to faster diffusion across MT protofilaments. Taken together, our results explain experimentally observed data and shed light on the roles played by disordered tubulin tails and tail modifications in the molecular mechanism of protein diffusion along MTs.

Understanding the Role of the Corporation in Sustainability Transitions

2019 ◽  
Vol 32 (2) ◽  
pp. 87-97 ◽  
Author(s):  
Magali A. Delmas ◽  
Thomas P. Lyon ◽  
John W. Maxwell
Keyword(s):  
Case Studies ◽  
Large Scale ◽  
Systemic Change ◽  
Coalition Building ◽  
Sustainability Transitions ◽  
Study Approach ◽  
Responsible Investing ◽  
Information Strategies ◽  
Wide Range

The state of the planet calls for large-scale sustainability transitions involving systemic adoption of markedly better environmental and social practices. The objective of this symposium is to better understand the role of corporations in promoting such systemic change. We present four case studies—representing diverse industries and change mechanisms—-to investigate corporate leadership in sustainability transitions. The cases examine a wide range of mechanisms used by corporations to progress toward sustainability, such as political coalition building and information strategies through eco-labels, socially responsible investing, and the public statements of CEOs. In this introduction, we discuss the challenges associated with both achieving and studying systemic change, explain the rationale for a case study approach, describe the findings from the case studies, and draw some general conclusions on the mechanisms by which firms may be able to lead, or at least participate in, systemic change in the different phases of sustainability transitions.

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