Local Structural Changes Research Articles

Coupling structural evolution and oxygen-redox electrochemistry in layered transition metal oxides.

Lattice oxygen redox offers an unexplored way to access superior electrochemical properties of transition metal oxides (TMOs) for rechargeable batteries. However, the reaction is often accompanied by unfavourable structural transformations and persistent electrochemical degradation, thereby precluding the practical application of this strategy. Here we explore the close interplay between the local structural change and oxygen electrochemistry during short- and long-term battery operation for layered TMOs. The substantially distinct evolution of the oxygen-redox activity and reversibility are demonstrated to stem from the different cation-migration mechanisms during the dynamic de/intercalation process. We show that the π stabilization on the oxygen oxidation initially aids in the reversibility of the oxygen redox and is predominant in the absence of cation migrations; however, the π-interacting oxygen is gradually replaced by σ-interacting oxygen that triggers the formation of O-O dimers and structural destabilization as cycling progresses. More importantly, it is revealed that the distinct cation-migration paths available in the layered TMOs govern the conversion kinetics from π to σ interactions. These findings constitute a step forward in unravelling the correlation between the local structural evolution and the reversibility of oxygen electrochemistry and provide guidance for further development of oxygen-redox layered electrode materials.

Theoretical investigations on the effects of mutations in important residues of NS1B on its RNA-binding using molecular dynamics simulations

NS1B protein plays an important role in countering host antiviral defense and virulence of influenza virus B, considered as the promising target. The first experimental structure of the NS1B protein has recently been determined, was able to bind to double-stranded RNA (dsRNA). However, few studies attempt to investigate the RNA-binding mechanism of the NS1B. In this study, we provide our understanding of the structure-function relationship, dynamics and RNA-binding mechanism of the NS1B protein by performing molecular dynamics simulations combined and MM-GBSA calculations on the NS1B-dsRNA complex. 12 key residues are identified for RNA-binding by forming hydrogen bonds with the. Our results also demonstrate that mutations (R156A, K160A, R208A and K221A) can cause the local structure changes of NS1B CTD and the hydrogen bonds between NS1B CTD and RNA disappearance, which may be the main reasons for the decrease in RNA-binding affinity. These results mentioned will help us understanding the RNA-binding mechanism and could provide some medicinal chemistry insights chances for rational drug design targeting NS1B protein.

Crystal structure of SFPQ-NONO heterodimer

The Drosophila behavior/human splicing (DBHS) protein family is composed of the three members SFPQ, NONO and PSPC1. These proteins share a strong sequence and structural homology within the core-structured domains forming obligate homo- and heterodimers. This feature may lead to the simultaneous existence of six different dimeric complexes that sustain their function in many cellular processes such as pre-mRNA splicing, innate immunity, transcriptional regulation. In order to perform a complete structural analysis of all possible DBHS dimers, we have solved the crystal structure of the missing DBHS heterodimer SFPQ-NONO at 3.0 Å resolution. We identify subtle changes in amino acid composition and local secondary structure of the NOPS region orientation that may modulate affinity between complexes. Interestingly this area is found mutated in aggressive skin cancers and adenocarcinomas.

Vibrational properties of CuInP2S6 across the ferroelectric transition

In order to explore the properties of a two-sublattice ferroelectric, we measured the infrared and Raman scattering response of CuInP2S6 across the ferroelectric and glassy transitions and compared our findings to a symmetry analysis, calculations of phase stability, and lattice dynamics. In addition to uncovering displacive character and a large hysteresis region surrounding the ferroelectric transition temperature T_C, we identify the vibrational modes that stabilize the polar phase and confirm the presence of two ferroelectric variants with opposite polarizations. Below TC, a poorly understood relaxational or glassy transition at Tg is characterized by local structure changes in the form of subtle peak shifting and activation of low frequency out-of-plane Cu- and In-containing modes. The latter are due to changes in the Cu/In coordination environments and associated order-disorder processes. Moreover, Tg takes place in two steps with another large hysteresis region and significant underlying scattering. Combined with imaging of the room temperature phase separation, this effort lays the groundwork for studying CuInP2S6 under external stimuli and in the ultra-thin limit.

The pathogenic R5L mutation disrupts formation of Tau complexes on the microtubule by altering local N-terminal structure

The microtubule-associated protein (MAP) Tau is an intrinsically disordered protein (IDP) primarily expressed in axons, where it functions to regulate microtubule dynamics, modulate motor protein motility, and participate in signaling cascades. Tau misregulation and point mutations are linked to neurodegenerative diseases, including progressive supranuclear palsy (PSP), Pick's disease, and Alzheimer's disease. Many disease-associated mutations in Tau occur in the C-terminal microtubule-binding domain of the protein. Effects of C-terminal mutations in Tau have led to the widely accepted disease-state theory that missense mutations in Tau reduce microtubule-binding affinity or increase Tau propensity to aggregate. Here, we investigate the effect of an N-terminal arginine to leucine mutation at position 5 in Tau (R5L), associated with PSP, on Tau-microtubule interactions using an invitro reconstituted system. Contrary to the canonical disease-state theory, we determine that the R5L mutation does not reduce Tau affinity for the microtubule using total internal reflection fluorescence microscopy. Rather, the R5L mutation decreases the ability of Tau to form larger-order complexes, or Tau patches, at high concentrations of Tau. Using NMR, we show that the R5L mutation results in a local structural change that reduces interactions of the projection domain in the presence of microtubules. Altogether, these results challenge both the current paradigm of how mutations in Tau lead to disease and the role of the projection domain in modulating Tau behavior on the microtubule surface.

Structural effects of disease related mutations in actin binding period 3 of tropomyosin

Tropomyosin (Tpm) is an actin-binding coiled-coil protein, which in muscle regulates contraction in troponin/Ca2+-dependent manner and length of the thin filament at the pointed end. Due to its size and multidomain structure, it is difficult to observe small local structural changes in the coiled coil caused by some disease-related mutations. In this study, we designed 97-residue peptides, Tpm3.1265-155 and Tpm1.164-154, focusing on the period-3 region of two Tpm isoforms. Using these peptides, we evaluated the effects of cardiomyopathy mutations located in this region: I92T and V95A in Tpm1.1, and congenital myopathy mutations R91P and R91C in Tpm3.12.

The spatial dissemination of COVID-19 and associated socio-economic consequences.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has wreaked havoc worldwide with millions of lives claimed, human travel restricted and economic development halted. Leveraging city-level mobility and case data, our analysis shows that the spatial dissemination of COVID-19 can be well explained by a local diffusion process in the mobility network rather than a global diffusion process, indicating the effectiveness of the implemented disease prevention and control measures. Based on the constructed case prediction model, it is estimated that there could be distinct social consequences if the COVID-19 outbreak happened in different areas. During the epidemic control period, human mobility experienced substantial reductions and the mobility network underwent remarkable local and global structural changes toward containing the spread of COVID-19. Our work has important implications for the mitigation of disease and the evaluation of the socio-economic consequences of COVID-19 on society.

Discovery and Characterization of a Cryptic Secondary Binding Site in the Molecular Chaperone HSP70.

Heat Shock Protein 70s (HSP70s) are key molecular chaperones that are overexpressed in many cancers and often associated with metastasis and poor prognosis. It has proven difficult to develop ATP-competitive, drug-like small molecule inhibitors of HSP70s due to the flexible and hydrophilic nature of the HSP70 ATP-binding site and its high affinity for endogenous nucleotides. The aim of this study was to explore the potential for the inhibition of HSP70 through alternative binding sites using fragment-based approaches. A surface plasmon resonance (SPR) fragment screen designed to detect secondary binding sites in HSP70 led to the identification by X-ray crystallography of a cryptic binding site in the nucleotide-binding domain (NBD) of HSP70 adjacent to the ATP-binding site. Fragment binding was confirmed and characterized as ATP-competitive using SPR and ligand-observed NMR methods. Molecular dynamics simulations were applied to understand the interactions with the protein upon ligand binding, and local secondary structure changes consistent with interconversion between the observed crystal structures with and without the cryptic pocket were detected. A virtual high-throughput screen (vHTS) against the cryptic pocket was conducted, and five compounds with diverse chemical scaffolds were confirmed to bind to HSP70 with micromolar affinity by SPR. These results identified and characterized a new targetable site on HSP70. While targeting HSP70 remains challenging, the new site may provide opportunities to develop allosteric ATP-competitive inhibitors with differentiated physicochemical properties from current series.

Morphological development of the human fetal striatum during the second trimester.

The morphological development of the fetal striatum during the second trimester has remained poorly described. We manually segmented the striatum using 7.0-T MR images of the fetal specimens ranging from 14 to 22 gestational weeks. The global development of the striatum was evaluated by volume measurement. The absolute volume (Vabs) of the caudate nucleus (CN) increased linearly with gestational age, while the relative volume (Vrel) showed a quadratic growth. Both Vabs and Vrel of putamen increased linearly. Through shape analysis, the changes of local structure in developing striatum were specifically demonstrated. Except for the CN tail, the lateral and medial parts of the CN grew faster than the middle regions, with a clear rostral-caudal growth gradient as well as a distinct "outside-in" growth gradient. For putamen, the dorsal and ventral regions grew obviously faster than the other regions, with a dorsal-ventral bidirectional developmental pattern. The right CN was larger than the left, whereas there was no significant hemispheric asymmetry in the putamen. By establishing the developmental trajectories, spatial heterochrony, and hemispheric dimorphism of human fetal striatum, these data bring new insight into the fetal striatum development and provide detailed anatomical references for future striatal studies.

Amphoteric behavior of component and microstructure feature on CaO-Al2O3-TiO2 ternary melt by molecular dynamics simulation

Amphoteric oxides, Al2O3 and TiO2, are essential compositions in metallurgical melts and have an important role in regulating slag performance. In this study, the structural characteristics of the CaO-Al2O3-TiO2 ternary melt, such as local structural order and particle coordination changes, are investigated by molecular dynamics simulation. The effects of Al2O3 and TiO2 on the microstructure of various melts and their role differences are analyzed. The results show that the amphoteric behavior of TiO2 dominate with low titanium concentration ranging from 3 mol% to 18 mol%. It promotes the change of Al2O3 from acidic to alkaline. Meanwhile, the value of (NBO/T) increases and the melt’s viscosity decreases. In addition, the amphoteric behavior of TiO2 dominate in the high titanium system, ranging from 52 mol% to 66 mol% of TiO2 concentration. It promotes the conversion of TiO2 to alkaline. Meanwhile, the melt polymerization and viscosity are enhanced. As for the ‘aluminum avoidance principle’, it only applies to low-titanium system and invalid in high-titanium system.

Chemical and Structural Alterations in the Amorphous Structure of Obsidian due to Nanolites.

Obsidian is volcanic glass that results from the rapid cooling of silica-rich melt. Nanoscale crystallites precipitate out of the melt prior to solidification and remain embedded in the amorphous matrix. These crystallites provide information on the flow kinetics and composition of the melt. Due to the sparsity and size of nanolites, studies often focus on supramicron crystallites. This research takes advantage of the conchoidal fracture of obsidian by knapping samples with nanometer-thin edges for transmission electron microscopy characterization. Nanolites in the amorphous matrix are studied using energy-dispersive spectroscopy (EDS) and electron diffraction. Certain alkali and alkaline-earth cations exhibit patterns of depletion near Fe-oxide nanolites. EDS is used to identify nanolites and variations in the composition of the matrix. Parallel beam diffraction and radial distribution function analysis of nearest-neighbor distances determine average bond lengths in the matrix near nanolites, showing that nanolites influence the nearby short-range ordering and atomic character of the matrix. Analysis reveals decreased mean nearest-neighbor distances in the matrix adjacent to nanolites compared to the bulk. Our methods exhibit the required sensitivity to detect variations in the composition and structure near nanolites, and our findings indicate that obsidian nanolites contribute to quantifiable localized changes in the amorphous structure.

Structural characterization of interfaces in silica core-alumina shell microspheres by solid-state NMR spectroscopy

Atomic-scale description of surfaces and interfaces in core-shell aluminosilicate materials is not fully elucidated, partially due to their amorphous character and complex mechanisms that govern their properties. In this paper, new insights into nanostructured core-shell aluminosilicates have been demonstrated, by using different solid-state NMR methods, i.e 29Si, 29Si cross-polarization (CP), 27Al, 27Al triple-quantum (3Q), and 1H–27Al heteronuclear correlation (HETCOR) MAS NMR. For this purpose, nanostructured silica core-alumina shell microspheres, undoped and doped with gadolinium ions respectively, obtained by a chemical synthesis based on the Stöber method for the silica core and electrostatic attraction for developing the alumina shell were studied. As a result, a new alumino-silicate layer formation was proved at the interface between silica core, where aluminum diffuses, on small scale, in the silica network, and alumina shell, where silicon ions migrate, on a larger scale, in the alumina network, leading to a stable core-shell structure. Moreover, this process is accompanied by significant local structural changes in the transition zone, particularly at the aluminum neighborhood, which is quite well understood now, with the power of solid-state NMR spectroscopy.

Role of helical structure and dynamics in oligoadenylate synthetase 1 (OAS1) mismatch tolerance and activation by short dsRNAs

The 2'-5'-oligoadenylate synthetases (OAS) are innate immune sensors of cytosolic double-stranded RNA (dsRNA) that play a critical role in limiting viral infection. How these proteins are able to avoid aberrant activation by cellular RNAs is not fully understood, but adenosine-to-inosine (A-to-I) editing has been proposed to limit accumulation of endogenous RNAs that might otherwise cause stimulation of the OAS/RNase L pathway. Here, we aim to uncover whether and how such sequence modifications can restrict the ability of short, defined dsRNAs to activate the single-domain form of OAS, OAS1. Unexpectedly, we find that all tested inosine-containing dsRNAs have an increased capacity to activate OAS1, whether in a destabilizing (I•U) or standard Watson-Crick-like base pairing (I-C) context. Additional variants with strongly destabilizing A•C mismatches or stabilizing G-C pairs also exhibit increased capacity to activate OAS1, eliminating helical stability as a factor in the relative ability of the dsRNAs to activate OAS1. Using thermal difference spectra and molecular dynamics simulations, we identify both increased helical dynamics and specific local changes in helical structure as important factors in the capacity of short dsRNAs to activate OAS1. These helical features may facilitate more ready adoption of the distorted OAS1-bound conformation or stabilize important structures to predispose the dsRNA for optimal binding and activation of OAS1. These studies thus reveal the molecular basis for the greater capacity of some short dsRNAs to activate OAS1 in a sequence-independent manner.

Study of Local Structural Changes on Air Cooling at the End of Rotor Windings for Variable Speed Pumped Storage Generator-Motor

The shrink fit retaining ring is currently the easiest to install and the most widely used end fixed for structure AC excitation variable speed generator-motor rotor end windings. However, the current research on the effect of high strength sealing on the ventilation and heat dissipation performance of the end is not enough. In this paper, based on the actual structural parameters and periodic symmetry simplification, the three-dimensional coupled calculation model of fluid field and temperature field is established. After solving the fluid and thermal equations, the influence of the length of rotor support block, the height of rotor support block, and the number of rotor support block on the fluid flow and temperature distribution in the rotor end region of generator-motor is studied using the finite volume method. The rheological characteristics of the air in the rotor domain, such as velocity and inter-winding flow, are analyzed. The law of temperature variation with local structure in the computational domain is studied. The variation law of cooling medium performance inside the large variable speed power generator motor is revealed.

The effects of glycine to alanine mutations on the structure of GPO collagen model peptides.

Collagen proteins are the main constituents of the extracellular matrix (ECM), and fulfil a number of wide-ranging functions, including contributions to the mechanical and biological behaviour of the ECM. Due to the heterogeneous nature of collagen in tissue samples it is difficult to fully explain the experimental observation, and hence the study of shorter model peptides is common place. Here, the computational energy landscape framework is employed to study Gly to Ala mutations in a GPO model peptide. The results show good agreement with the experimental observations for the GPO reference and a triply mutated peptide, demonstrating the validity of the approach. The modelling predicts that changes in structure are moderate and localised, with an increased dynamic in the backbone and alterations to the hydrogen bonding pattern. Two mechanisms for adjusting to the mutations are observed, with potential consequences regarding protein binding. Finally, in line with a hypothesis that proline puckering allows controlled flexibility (Chow et al., Sci. Rep., 2018, 8, 13809), alterations in the puckering preferences are observed in the strained residues surrounding the mutational sites.

Structural insights into Lewis acid- and F4TCNQ-doped conjugated polymers by solid-state magnetic resonance spectroscopy.

Molecular doping strategies facilitate orders of magnitude enhancement in the charge carrier mobility of organic semiconductors (OSCs). Understanding the different doping mechanisms and molecular-level constraints on doping efficiency related to the material energy levels is crucial to develop versatile dopants for OSCs. Given the compositional and structural heterogeneities associated with OSC thin films, insight into dopant-polymer interactions by long-range techniques such as X-ray scattering and electron microscopy is exceedingly challenging to obtain. This study employs short-range probes, solid-state (ss)NMR and EPR spectroscopy, to resolve local structures and intermolecular interactions between dopants such as F4TCNQ (2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane), Lewis acid BCF (tris[pentafluorophenyl] borane) and Lewis base conjugated polymer, PCPDTBT (P4) (poly[2,6-(4,4-bis(2-hexadecyl)-4H-cyclopenta[2,1-b;3,4-b']dithiophene)-alt-4,7(2,1,3-benzothiadiazole)]). Analysis of 1H and 13C ssNMR spectra of P4, P4 : F4TCNQ and P4 : BCF blends indicates that the addition of dopants induces local structural changes in the P4 polymer, and causes paramagnetism-induced signal broadening and intensity losses. The hyperfine interactions in P4 : BCF and P4 : F4TCNQ are characterized by two-dimensional pulsed EPR spectroscopy. For P4 : F4TCNQ, 19F ssNMR analysis indicates that the F4TCNQ molecules are distributed and aggregated into different local chemical environments. By comparison, BCF molecules are intermixed with the P4 polymer and interact with traces of water molecules to form BCF-water complexes that serve as Brønsted acid sites, as revealed by 11B ssNMR spectroscopy. These results indicate that the P4-dopant blends exhibit complex morphology with different distributions of dopants, whereby the combined use of ssNMR and EPR provides essential insights into how higher doping efficiency is observed with BCF and a mediocre efficiency is associated with F4TCNQ molecules.

Bulk and surface exsolution produces a variety of Fe-rich and Fe-depleted ellipsoidal nanostructures in La0.6Sr0.4FeO3 thin films.

The past several years have seen a resurgence in the popularity of metal exsolution as an approach to synthesize advanced materials proposed for novel catalytic, magnetic, optical, and electrochemical properties. Whereas most studies to-date have focused on surface exsolution (motivated by catalysis), we instead report on the diversity of nanostructures formed in La0.6Sr0.4FeO3 thin films during sub-surface or so-called 'bulk' exsolution, in addition to surface exsolution. Bulk exsolution is a promising approach to tuning the functionality of materials, yet there is little understanding of the nanostructures exsolved within the bulk and how they compare to those exsolved at gas-solid interfaces. This work combines atomic- and nano-scale imaging and spectroscopy techniques applied using a state-of-the-art aberration-corrected scanning transmission electron microscope (STEM). In doing so, we present a detailed atomic-resolution study of a range of Fe-rich and Fe-depleted nanostructures possible via exsolution, along with qualitative and quantitative chemical analysis of the exsolved nanostructures and oxide phases formed throughout the film. Local structural changes in the perovskite matrix, coinciding with nanostructure exsolution, are also characterized with atomic-resolution STEM imaging. Fe exsolution is shown to create local A-site rich domains of Ruddlesden-Popper phase, and some stages of this phase formation have been demonstrated in this work. In particular, phase boundaries are found to be the primary nucleation sites for bulk and surface exsolution, and the exsolved particles observed here tend to be ellipsoidal with shape factor of 1.4. We report a range of nanostructure types (core-shell, bulk core-shell, adjacent, and independent particles), revealing several possible avenues of future exploration aimed to understand the formation mechanism of each exsolution type and to develop their functionality. This work is thus relevant to materials scientists and engineers motivated to understand and utilize exsolution to synthesize materials with predictable nanostructures.

Tracking local and global structural changes in a protein by cold ion spectroscopy.

Characterization of native structures of proteins in the gas phase remains challenging due to the unpredictable conformational changes the molecules undergo during desolvation and ionization. We spectroscopically studied cryogenically cooled protonated protein ubiquitin and its microhydrated complexes prepared in the gas phase in a range of charge states under different ionization conditions. The UV spectra appear vibrationally resolved for the unfolded protein, but become redshifted and smooth for the native-like structures of ubiquitin. This spectroscopic change results from the H-bonding of the hydroxyl of Tyr to the amide group of Glu-51 in the compact structures; the minimum length of this bond was estimated to be ∼1.7 Å. IR spectroscopy reflects the global structural change by observing redshifts of free NH/OH-stretch vibrational transitions. Evaporative cooling of microhydrated complexes of ubiquitin keeps the protein chilly during ionization, enabling native-like conformers with up to eight protons to survive in the gas phase.

Relaxor–super-paraelectric behaviour and crystal-field–driven spin-phonon coupling in pyrochlore Eu2Ti2O7

The temperature-dependent Raman spectroscopy and dielectric property of pyrochlore Eu2Ti2O7 have been investigated. The appearance of additional phonon modes below 200 K is observed suggesting a local structural change. The anomalous softening of the phonon modes and existence of crystal-field-induced short-range magnetic ordering below 150 K unveiled the possible spin-phonon coupling. The signature behaviour of a dipolar glassy-relaxor state and super-paraelectric nature has been demonstrated. Additional dielectric anomaly at lower temperature, below 40 K, related to spin-spin correlation has also been reported.

X-ray Transient Absorption Studies of Exciton Self-Trapping

We present optical pump/X-ray absorption probe studies to probe changes in electronic distribution and local structure upon formation of a self-trapped exciton. The experiments were carried out on the mixed-valence halide-bridged transition metal linear chain charge density wave material [Pt(en2)][Pt(en2)Cl2]·(ClO4)4. Photoinduced changes in the Pt LIII XANES spectrum were measured on a picosecond time scale following generation of excitons via optical excitation of the intervalence charge transfer transition. Ab initio FEFF9 modeling of the spectra and the associated angular momentum projected density of states was used to interpret the response. We find photoinduced changes reflecting electronic redistribution and local lattice distortions that correspond to strong localization of the self-trapped state.