scholarly journals Unbiased Atomistic Insight in the Mechanisms and Solvent Role for Globular Protein Dimer Dissociation

2018 ◽  
Author(s):  
Faidon Z. Brotzakis ◽  
Peter G. Bolhuis
Keyword(s):  
Transition State ◽  
Degrees Of Freedom ◽  
Process Analysis ◽  
Salt Bridge ◽  
Underlying Mechanism ◽  
Full Detail ◽  
Hydration Water ◽  
Native Contact ◽  
Reorientation Dynamics

Association and dissociation of proteins are fundamental processes in nature. While this process is simple to understand conceptually, the details of the underlying mechanism and role of the solvent are poorly understood. Here we investigate the mechanism and solvent role for the dissociation of the hydrophilic β-lactoglobulin dimer by employing transition path sampling. Analysis of the sampled path ensembles indicates that dissociation (and association) occurs via a variety of mechanisms: 1) a direct aligned dissociation 2) a hopping and rebinding transition followed by unbinding 3) a sliding transition before unbinding. Reaction coordinate and transition state analysis predicts that, besides native contact and vicinity salt-bridge interactions, solvent degrees of freedom play an important role in the dissociation process. Analysis of the structure and dynamics of the solvent molecules reveals that the dry native interface induces enhanced populations of both disordered hydration water and hydration water with higher tetrahedrality, mainly nearby hydrophobic residues. Bridging waters, hydrogen bonded to both proteins, support contacts, and exhibit a faster decay and reorientation dynamics in the transition state than in the native state interface, which renders the proteins more mobile and assists in rebinding. While not exhaustive, our sampling of rare un-biased reactive molecular dynamics trajectories shows in full detail how proteins can dissociate via complex pathways including (multiple) rebinding events. The atomistic insight obtained assists in further understanding and control of the dynamics of protein-protein interaction including the role of solvent.PACS numbers:

On the Use of Quantum Thermal Bath in Unimolecular Fragmentation Simulations

2019 ◽  
Author(s):  
Riccardo Spezia ◽  
Hichem Dammak
Keyword(s):  
Degrees Of Freedom ◽  
Molecular Simulations ◽  
Zero Point ◽  
Thermal Bath ◽  
Unimolecular Dissociation ◽  
Point Energy ◽  
Rotational Degrees Of Freedom ◽  
The Difference ◽  
Nuclear Effects

<div> <div> <div> <p>In the present work we have investigated the possibility of using the Quantum Thermal Bath (QTB) method in molecular simulations of unimolecular dissociation processes. Notably, QTB is aimed in introducing quantum nuclear effects with a com- putational time which is basically the same as in newtonian simulations. At this end we have considered the model fragmentation of CH4 for which an analytical function is present in the literature. Moreover, based on the same model a microcanonical algorithm which monitor zero-point energy of products, and eventually modifies tra- jectories, was recently proposed. We have thus compared classical and quantum rate constant with these different models. QTB seems to correctly reproduce some quantum features, in particular the difference between classical and quantum activation energies, making it a promising method to study unimolecular fragmentation of much complex systems with molecular simulations. The role of QTB thermostat on rotational degrees of freedom is also analyzed and discussed. </p> </div> </div> </div>

scholarly journals Dzyaloshinskii–Moriya interaction in noncentrosymmetric superlattices

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Woo Seung Ham ◽  
Abdul-Muizz Pradipto ◽  
Kay Yakushiji ◽  
Kwangsu Kim ◽  
Sonny H. Rhim ◽  
...  
Keyword(s):  
Heavy Metal ◽  
Degrees Of Freedom ◽  
Orbit Coupling ◽  
Inversion Symmetry ◽  
Spin Orbit Coupling ◽  
Spin Orbit ◽  
Band Formation ◽  
Research Activities ◽  
Moriya Interaction

AbstractDzyaloshinskii–Moriya interaction (DMI) is considered as one of the most important energies for specific chiral textures such as magnetic skyrmions. The keys of generating DMI are the absence of structural inversion symmetry and exchange energy with spin–orbit coupling. Therefore, a vast majority of research activities about DMI are mainly limited to heavy metal/ferromagnet bilayer systems, only focusing on their interfaces. Here, we report an asymmetric band formation in a superlattices (SL) which arises from inversion symmetry breaking in stacking order of atomic layers, implying the role of bulk-like contribution. Such bulk DMI is more than 300% larger than simple sum of interfacial contribution. Moreover, the asymmetric band is largely affected by strong spin–orbit coupling, showing crucial role of a heavy metal even in the non-interfacial origin of DMI. Our work provides more degrees of freedom to design chiral magnets for spintronics applications.

scholarly journals A Superfluid Perspective on Neutron Star Dynamics

Universe ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. 17
Author(s):  
Nils Andersson
Keyword(s):  
Neutron Star ◽  
Degrees Of Freedom ◽  
Temperature Scale ◽  
Fluid System ◽  
Fluid Core ◽  
State Of Matter ◽  
Entrainment Effect ◽  
Neutron Component ◽  
The Impact

As mature neutron stars are cold (on the relevant temperature scale), one has to carefully consider the state of matter in their interior. The outer kilometre or so is expected to freeze to form an elastic crust of increasingly neutron-rich nuclei, coexisting with a superfluid neutron component, while the star’s fluid core contains a mixed superfluid/superconductor. The dynamics of the star depend heavily on the parameters associated with the different phases. The presence of superfluidity brings new degrees of freedom—in essence we are dealing with a complex multi-fluid system—and additional features: bulk rotation is supported by a dense array of quantised vortices, which introduce dissipation via mutual friction, and the motion of the superfluid is affected by the so-called entrainment effect. This brief survey provides an introduction to—along with a commentary on our current understanding of—these dynamical aspects, paying particular attention to the role of entrainment, and outlines the impact of superfluidity on neutron-star seismology.

scholarly journals Higher spins from exotic dualisations

2021 ◽  
Vol 2021 (3) ◽  
Author(s):  
Nicolas Boulanger ◽  
Victor Lekeu
Keyword(s):  
Infinite Number ◽  
Arbitrary Number ◽  
Degrees Of Freedom ◽  
Young Tableaux ◽  
Spacetime Dimension ◽  
Massless Field ◽  
Free Level ◽  
Higher Spins

Abstract At the free level, a given massless field can be described by an infinite number of different potentials related to each other by dualities. In terms of Young tableaux, dualities replace any number of columns of height hi by columns of height D − 2 − hi, where D is the spacetime dimension: in particular, applying this operation to empty columns gives rise to potentials containing an arbitrary number of groups of D − 2 extra antisymmetric indices. Using the method of parent actions, action principles including these potentials, but also extra fields, can be derived from the usual ones. In this paper, we revisit this off-shell duality and clarify the counting of degrees of freedom and the role of the extra fields. Among others, we consider the examples of the double dual graviton in D = 5 and two cases, one topological and one dynamical, of exotic dualities leading to spin three fields in D = 3.

scholarly journals Kindlin-2 mediates mechanotransduction in bone by regulating expression of Sclerostin in osteocytes

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Lei Qin ◽  
Xuekun Fu ◽  
Jing Ma ◽  
Manxia Lin ◽  
Peijun Zhang ◽  
...  
Keyword(s):  
Bone Loss ◽  
Mechanical Stimulation ◽  
Fluid Shear Stress ◽  
Weight Bearing ◽  
Underlying Mechanism ◽  
Long Bones ◽  
Cell Orientation ◽  
Cytoskeleton Organization

AbstractOsteocytes act as mechanosensors in bone; however, the underlying mechanism remains poorly understood. Here we report that deleting Kindlin-2 in osteocytes causes severe osteopenia and mechanical property defects in weight-bearing long bones, but not in non-weight-bearing calvariae. Kindlin-2 loss in osteocytes impairs skeletal responses to mechanical stimulation in long bones. Control and cKO mice display similar bone loss induced by unloading. However, unlike control mice, cKO mice fail to restore lost bone after reloading. Osteocyte Kindlin-2 deletion impairs focal adhesion (FA) formation, cytoskeleton organization and cell orientation in vitro and in bone. Fluid shear stress dose-dependently increases Kindlin-2 expression and decreases that of Sclerostin by downregulating Smad2/3 in osteocytes; this latter response is abolished by Kindlin-2 ablation. Kindlin-2-deficient osteocytes express abundant Sclerostin, contributing to bone loss in cKO mice. Collectively, we demonstrate an indispensable novel role of Kindlin-2 in maintaining skeletal responses to mechanical stimulation by inhibiting Sclerostin expression during osteocyte mechanotransduction.

scholarly journals Rspo3 regulates the abnormal differentiation of small intestinal epithelial cells in diabetic state

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ti-Dong Shan ◽  
Han Yue ◽  
Xue-Guo Sun ◽  
Yue-Ping Jiang ◽  
Li Chen
Keyword(s):  
Epithelial Cells ◽  
Bioinformatics Analysis ◽  
Intestinal Epithelial Cells ◽  
Underlying Mechanism ◽  
Luciferase Reporter ◽  
Intestinal Epithelial ◽  
Epithelial Stem Cells ◽  
Diabetic State ◽  
Definitive Evidence

Abstract Background The complications caused by diabetes mellitus (DM) are the focus of clinical treatment. However, little is known about diabetic enteropathy (DE) and its potential underlying mechanism. Methods Intestinal epithelial cells (IECs) and intestinal epithelial stem cells (IESCs) were harvested from BKS.Cg-Dock7m+/+Leprdb/JNju (DM) mice, and the expression of R-Spondin 3 (Rspo3) was detected by RT-qPCR, Western blotting, immunohistochemistry, and immunofluorescence. The role of Rspo3 in the abnormal differentiation of IECs during DM was confirmed by knockdown experiments. Through miRNA expression profiling, bioinformatics analysis, and RT-qPCR, we further analyzed the differentiation-related miRNAs in the IECs from mice with DM. Results Abnormal differentiation of IECs was observed in the mice with DM. The expression of Rspo3 was upregulated in the IECs from the mice with DM. This phenomenon was associated with Rspo3 overexpression. Additionally, Rspo3 is a major determinant of Lgr5+ stem cell identity in the diabetic state. Microarray analysis, bioinformatics analysis, and luciferase reporter assays revealed that microRNA (miR)-380-5p directly targeted Rspo3. Moreover, miR-380-5p upregulation was observed to attenuate the abnormal differentiation of IECs by regulating Rspo3 expression. Conclusions Together, our results provide definitive evidence of the essential role of Rspo3 in the differentiation of IECs in DM.

scholarly journals Reduction of 3-Deoxyglucosone by Epigallocatechin Gallate Results Partially from an Addition Reaction: The Possible Mechanism of Decreased 5-Hydroxymethylfurfural in Epigallocatechin Gallate-Treated Black Garlic

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4746
Author(s):  
An-Ting Tu ◽  
Jer-An Lin ◽  
Chieh-Hsiu Lee ◽  
Yi-An Chen ◽  
Jung-Tsung Wu ◽  
...  
Keyword(s):  
Intermediate Product ◽  
Aging Process ◽  
Addition Reaction ◽  
Reaction System ◽  
Epigallocatechin Gallate ◽  
Structural Identification ◽  
Underlying Mechanism ◽  
Harmful Substance ◽  
Relevant Research

5-Hydroxymethylfurfural (5-HMF) is a harmful substance generated during the processing of black garlic. Our previous research demonstrated that impregnation of black garlic with epigallocatechin gallate (EGCG) could reduce the formation of 5-HMF. However, there is still a lack of relevant research on the mechanism and structural identification of EGCG inhibiting the production of 5-HMF. In this study, an intermediate product of 5-HMF, 3-deoxyglucosone (3-DG), was found to be decreased in black garlic during the aging process, and impregnation with EGCG for 24 h further reduced the formation of 3-DG by approximately 60% in black garlic compared with that in the untreated control. The aging-mimicking reaction system of 3-DG + EGCG was employed to determine whether the reduction of 3-DG was the underlying mechanism of decreased 5-HMF formation in EGCG-treated black garlic. The results showed that EGCG accelerated the decrease of 3-DG and further attenuated 5-HMF formation, which may be caused by an additional reaction with 3-DG, as evidenced by LC-MS/MS analysis. In conclusion, this study provides new insights regarding the role of EGCG in blocking 5-HMF formation.

scholarly journals Roles of the C-Terminal Amino Acids of Non-Hexameric Helicases: Insights from Escherichia coli UvrD

2021 ◽  
Vol 22 (3) ◽  
pp. 1018
Author(s):  
Hiroaki Yokota
Keyword(s):  
Escherichia Coli ◽  
Amino Acids ◽  
Amino Acid ◽  
Single Molecule ◽  
Underlying Mechanism ◽  
Amino Acid Sequences ◽  
E Coli ◽  
X Ray Crystallography ◽  
Terminal Amino

Helicases are nucleic acid-unwinding enzymes that are involved in the maintenance of genome integrity. Several parts of the amino acid sequences of helicases are very similar, and these quite well-conserved amino acid sequences are termed “helicase motifs”. Previous studies by X-ray crystallography and single-molecule measurements have suggested a common underlying mechanism for their function. These studies indicate the role of the helicase motifs in unwinding nucleic acids. In contrast, the sequence and length of the C-terminal amino acids of helicases are highly variable. In this paper, I review past and recent studies that proposed helicase mechanisms and studies that investigated the roles of the C-terminal amino acids on helicase and dimerization activities, primarily on the non-hexermeric Escherichia coli (E. coli) UvrD helicase. Then, I center on my recent study of single-molecule direct visualization of a UvrD mutant lacking the C-terminal 40 amino acids (UvrDΔ40C) used in studies proposing the monomer helicase model. The study demonstrated that multiple UvrDΔ40C molecules jointly participated in DNA unwinding, presumably by forming an oligomer. Thus, the single-molecule observation addressed how the C-terminal amino acids affect the number of helicases bound to DNA, oligomerization, and unwinding activity, which can be applied to other helicases.

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