scholarly journals Torsional stress can regulate the unwrapping of two outer half superhelical turns of nucleosomal DNA

2021 ◽  
Vol 118 (7) ◽  
pp. e2020452118
Author(s):  
Hisashi Ishida ◽  
Hidetoshi Kono
Keyword(s):  
Large Scale ◽  
Stable State ◽  
Regulatory Proteins ◽  
Torsional Stress ◽  
Major Groove ◽  
Free Energies ◽  
Nucleosomal Dna ◽  
Inherent Nature ◽  
The Stability ◽  
Dynamics Simulations

Torsional stress has a significant impact on the structure and stability of the nucleosome. RNA polymerase imposes torsional stress on the DNA in chromatin and unwraps the DNA from the nucleosome to access the genetic information encoded in the DNA. To understand how the torsional stress affects the stability of the nucleosome, we examined the unwrapping of two half superhelical turns of nucleosomal DNA from either end of the DNA under torsional stress with all-atom molecular dynamics simulations. The free energies for unwrapping the DNA indicate that positive stress that overtwists DNA facilitates a large-scale asymmetric unwrapping of the DNA without a large extension of the DNA. During the unwrapping, one end of the DNA was dissociated from H3 and H2A-H2B, while the other end of the DNA stably remained wrapped. The detailed analysis indicates that this asymmetric dissociation is facilitated by the geometry and bendability of the DNA under positive stress. The geometry stabilized the interaction between the major groove of the twisted DNA and the H3 αN-helix, and the straightened DNA destabilized the interaction with H2A-H2B. Under negative stress, the DNA became more bendable and flexible, which facilitated the binding of the unwrapped DNA to the octamer in a stable state. Consequently, we conclude that the torsional stress has a significant impact on the affinity of the DNA and the octamer through the inherent nature of the DNA and can change the accessibility of regulatory proteins.

scholarly journals Binding of regulatory proteins to nucleosomes is modulated by dynamic histone tails

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yunhui Peng ◽  
Shuxiang Li ◽  
Alexey Onufriev ◽  
David Landsman ◽  
Anna R. Panchenko
Keyword(s):  
Regulatory Proteins ◽  
Binding Modes ◽  
Dna Interactions ◽  
Histone Tail ◽  
Histone Tails ◽  
Post Translational Modifications ◽  
Conformational Ensembles ◽  
Dna Accessibility ◽  
Nucleosomal Dna ◽  
Dynamics Simulations

AbstractLittle is known about the roles of histone tails in modulating nucleosomal DNA accessibility and its recognition by other macromolecules. Here we generate extensive atomic level conformational ensembles of histone tails in the context of the full nucleosome, totaling 65 microseconds of molecular dynamics simulations. We observe rapid conformational transitions between tail bound and unbound states, and characterize kinetic and thermodynamic properties of histone tail-DNA interactions. Different histone types exhibit distinct binding modes to specific DNA regions. Using a comprehensive set of experimental nucleosome complexes, we find that the majority of them target mutually exclusive regions with histone tails on nucleosomal/linker DNA around the super-helical locations ± 1, ± 2, and ± 7, and histone tails H3 and H4 contribute most to this process. These findings are explained within competitive binding and tail displacement models. Finally, we demonstrate the crosstalk between different histone tail post-translational modifications and mutations; those which change charge, suppress tail-DNA interactions and enhance histone tail dynamics and DNA accessibility.

scholarly journals FAILURE MECHANISM ANALYSIS CONSIDERS THE HYDROLOGICAL AND SEISMIC CONDITIONS AT CHASHAN SITE IN CENTRAL TAIWAN

2018 ◽  
Vol XLII-3/W4 ◽  
pp. 159-164
Author(s):  
M. C. Chung ◽  
C. H. Chen ◽  
T. L. Tai ◽  
M. M. Chen
Keyword(s):  
Water Level ◽  
Large Scale ◽  
Stable State ◽  
High Water ◽  
Mechanism Analysis ◽  
Scenario Simulation ◽  
Earthquake Scenarios ◽  
Hydrogeological Investigation ◽  
The Stability ◽  
Central Taiwan

<p><strong>Abstract.</strong> The investigation results of large-scale landslides in the central part of Taiwan from Central Geologic Survey identified a new, largescale landslide in the Chashan Village of Alishan Township, Chiayi County (ID: D160) which has the potential to influence the safety of Chashan Village residents. In coordination with the surface geological survey, Chashan site can be divided into three potential sliding areas (zones A, B and C). The paper uses GeoStudio for evaluating the stability of different hydrological and seismic scenarios. The results of scenario simulation show that: (1) In the normal and high water level scenarios, the safety factor obtained in zone A is greater than 1.0, and the initial judgment belongs to the stable state; (2) In the earthquake scenarios, the A4 potential sliding mass in zone A will be collapsed; (3) Through the scenario simulation, when the water level in zone A rises more than 25 meters or the PGA exceeds 160 gal, it is possible to cause the collapse of A4 potential sliding mass. The result of the study will contribute that the complex phenomenon between the stability of landslides and hydrogeological conditions can be revealed and clarified through the detailed study on the hydrogeological investigation, observation and the numerical simulation.</p>

scholarly journals Role of Long-range Allosteric Communication in Determining the Stability and Disassembly of SARS-COV-2 in Complex with ACE2

2020 ◽  
Author(s):  
Mauro L. Mugnai ◽  
Clark Templeton ◽  
Ron Elber ◽  
D. Thirumalai
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Long Range ◽  
Active Site ◽  
Large Scale ◽  
Conformational Transition ◽  
Network Models ◽  
Allosteric Communication ◽  
The Stability ◽  
Dynamics Simulations

AbstractSevere acute respiratory syndrome (SARS) and novel coronavirus disease (COVID-19) are caused by two closely related beta-coronaviruses, SARS-CoV and SARS-CoV-2, respectively. The envelopes surrounding these viruses are decorated with spike proteins, whose receptor binding domains (RBDs) initiate invasion by binding to the human angiotensin-converting enzyme 2 (ACE2). Subtle changes at the interface with ACE2 seem to be responsible for the enhanced affinity for the receptor of the SARS-CoV-2 RBD compared to SARS-CoV RBD. Here, we use Elastic Network Models (ENMs) to study the response of the viral RBDs and ACE2 upon dissassembly of the complexes. We identify a dominant detachment mode, in which the RBD rotates away from the surface of ACE2, while the receptor undergoes a conformational transition which stretches the active-site cleft. Using the Structural Perturbation Method, we determine the network of residues, referred to as the Allostery Wiring Diagram (AWD), which drives the large-scale motion activated by the detachment of the complex. The AWD for SARS-CoV and SARS-CoV-2 are remarkably similar, showing a network that spans the interface of the complex and reaches the active site of ACE2, thus establishing an allosteric connection between RBD binding and receptor catalytic function. Informed in part by the AWD, we used Molecular Dynamics simulations to probe the effect of interfacial mutations in which SARS-CoV-2 residues are replaced by their SARS-CoV counterparts. We focused on a conserved glycine (G502 in SARS-CoV-2, G488 in SARS-CoV) because it belongs to a region that initiates the dissociation of the complex along the dominant detachment mode, and is prominent in the AWD. Molecular Dynamics simulations of SARS-CoV-2 wild-type and G502P mutant show that the affinity for the human receptor of the mutant is drastically diminished. Our results suggest that in addition to residues that are in direct contact with the interface those involved in long range allosteric communication are also a determinant of the stability of the RBD-ACE2 complex.

The Role of Hydrophobicity in the Stability and pH-Switchability of (RXDX)4 and Coumarin-RXDX Conjugate β-Sheets

2020 ◽  
Author(s):  
Ryan Weber ◽  
Martin McCullagh
Keyword(s):  
Biological Imaging ◽  
Ph Sensing ◽  
Hydrophobic Residue ◽  
Ideal Candidate ◽  
Self Assembling ◽  
Sensing Applications ◽  
Β Sheets ◽  
The Stability ◽  
Dynamics Simulations

<p>pH-switchable, self-assembling materials are of interest in biological imaging and sensing applications. Here we propose that combining the pH-switchability of RXDX (X=Ala, Val, Leu, Ile, Phe) peptides and the optical properties of coumarin creates an ideal candidate for these materials. This suggestion is tested with a thorough set of all-atom molecular dynamics simulations. We first investigate the dependence of pH-switchabiliy on the identity of the hydrophobic residue, X, in the bare (RXDX)<sub>4</sub> systems. Increasing the hydrophobicity stabilizes the fiber which, in turn, reduces the pH-switchabilty of the system. This behavior is found to be somewhat transferable to systems in which a single hydrophobic residue is replaced with a coumarin containing amino acid. In this case, conjugates with X=Ala are found to be unstable and both pHs while conjugates with X=Val, Leu, Ile and Phe are found to form stable β-sheets at least at neutral pH. The (RFDF)<sub>4</sub>-coumarin conjugate is found to have the largest relative entropy value of 0.884 +/- 0.001 between neutral and acidic coumarin ordering distributions. Thus, we posit that coumarin-(RFDF)<sub>4</sub> containing peptide sequences are ideal candidates for pH-sensing bioelectronic materials.</p>

LANDSLIDE RISK MANAGEMENT IN THE COASTAL ZONE OF THE KUIBYSHEV RESERVOIR DUE THE DESIGN OF HIGH-SPEED LINE "MOSCOW-KAZAN"

2017 ◽  
Author(s):  
Nikolai Petrov ◽  
Nikolai Petrov ◽  
Inna Nikonorova ◽  
Inna Nikonorova ◽  
Vladimir Mashin ◽  
...  
Keyword(s):  
High Speed ◽  
Computational Models ◽  
Stable State ◽  
Landslide Risk ◽  
Kuibyshev Reservoir ◽  
Stepped Surface ◽  
The Stability ◽  
Landslide Slope ◽  
The Village

High-speed railway "Moscow-Kazan" by the draft crosses the Volga (Kuibyshev reservoir) in Chuvashia region 500 m below the village of New Kushnikovo. The crossing plot is a right-bank landslide slope with a stepped surface. Its height is 80 m; the slope steepness -15-16o. The authors should assess the risk of landslides and recommend anti-landslide measures to ensure the safety of the future bridge. For this landslide factors have been analyzed, slope stability assessment has been performed and recommendations have been suggested. The role of the following factors have been analyzed: 1) hydrologic - erosion and abrasion reservoir and runoff role; 2) lithologyc (the presence of Urzhum and Northern Dvina horizons of plastically deformable rocks, displacement areas); 3) hydrogeological (the role of perched, ground and interstratal water); 4) geomorphological (presence of the elemental composition of sliding systems and their structure in the relief); 5) exogeodynamic (cycles and stages of landslide systems development, mechanisms and relationship between landslide tiers of different generations and blocks contained in tiers). As a result 6-7 computational models at each of the three engineering-geological sections were made. The stability was evaluated by the method “of the leaning slope”. It is proved that the slope is in a very stable state and requires the following measures: 1) unloading (truncation) of active heads blocks of landslide tiers) and the edge of the plateau, 2) regulation of the surface and groundwater flow, 3) concrete dam, if necessary.

scholarly journals Development and Characterization of Two Types of Surface Displayed Levansucrases for Levan Biosynthesis

Catalysts ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 757
Author(s):  
Huiyi Shang ◽  
Danni Yang ◽  
Dairong Qiao ◽  
Hui Xu ◽  
Yi Cao
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Molecular Weight ◽  
Large Scale ◽  
Surface Display ◽  
Yeast Surface Display ◽  
Fusion Partner ◽  
Whole Cell ◽  
Food Industries ◽  
Yeast Surface ◽  
The Stability

Levan has wide applications in chemical, cosmetic, pharmaceutical and food industries. The free levansucrase is usually used in the biosynthesis of levan, but the poor reusability and low stability of free levansucrase have limited its large-scale use. To address this problem, the surface-displayed levansucrase in Saccharomyces cerevisiae were generated and evaluated in this study. The levansucrase from Zymomonas mobilis was displayed on the cell surface of Saccharomyces cerevisiae EBY100 using a various yeast surface display platform. The N-terminal fusion partner is based on a-agglutinin, and the C-terminal one is Flo1p. The yield of levan produced by these two whole-cell biocatalysts reaches 26 g/L and 34 g/L in 24 h, respectively. Meanwhile, the stability of the surface-displayed levansucrases is significantly enhanced. After six reuses, these two biocatalysts retained over 50% and 60% of their initial activities, respectively. Furthermore, the molecular weight and polydispersity test of the products suggested that the whole-cell biocatalyst of levansucrase displayed by Flo1p has more potentials in the production of levan with low molecular weight which is critical in certain applications. In conclusion, our method not only enable the possibility to reuse the enzyme, but also improves the stability of the enzyme.

scholarly journals INTRACISTRONIC MAPPING OF ELECTROPHORETIC SITES IN DROSOPHILA MELANOGASTER: FIDELITY OF INFORMATION TRANSFER BY GENE CONVERSION

Genetics ◽  
1974 ◽  
Vol 76 (2) ◽  
pp. 289-299
Author(s):  
Margaret McCarron ◽  
William Gelbart ◽  
Arthur Chovnick
Keyword(s):  
Drosophila Melanogaster ◽  
Information Transfer ◽  
Large Scale ◽  
Genetic Basis ◽  
Xanthine Dehydrogenase ◽  
Specific Protein ◽  
Wild Type ◽  
Electrophoretic Variation ◽  
The Stability ◽  
Recombination Experiments

ABSTRACT A convenient method is described for the intracistronic mapping of genetic sites responsible for electrophoretic variation of a specific protein in Drosophila melanogaster. A number of wild-type isoalleles of the rosy locus have been isolated which are associated with the production of electrophoretically distinguishable xanthine dehydrogenases. Large-scale recombination experiments were carried out involving null enzyme mutants induced on electrophoretically distinct wild-type isoalleles, the genetic basis for which is followed as a nonselective marker in the cross. Additionally, a large-scale recombination experiment was carried out involving null enzyme rosy mutants induced on the same wild-type isoallele. Examination of the electrophoretic character of crossover and convertant products recovered from the latter experiment revealed that all exhibited the same parental electrophoretic character. In addition to documenting the stability of the xanthine dehydrogenase electrophoretic character, this observation argues against a special mutagenesis hypothesis to explain conversions resulting from allele recombination studies.

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