Concerted Motion Research Articles

AuI(CN)2]-Armed [FeIII2FeII2] Square Complex Showing Unusual Spin-Crossover Behavior Due to a Symmetry-Breaking Phase Transition.

The incorporation of two different cyanide building blocks of [(TpR)FeIII(CN)3]- and [AuI(CN)2]- into one molecule afforded a novel hexanuclear [FeIII2FeII2AuI2] complex (1·2Et2O), in which the cyanide-bridged [FeIII2FeII2] square was further grafted by two [AuI(CN)2]- fragments as long arms in syn orientations. Complex 1·2Et2O undergoes a gradual spin crossover (SCO) ffrom low-spin (LS) to high-spin (HS) state for the Fe(II) centers upon desolvation. Remarkably, its desolvated phase (1) exhibits a reversible but atypical two-step (sharp-gradual) SCO behavior with considerable hysteresis (21 K). Variable-temperature single-crystal X-ray structural studies reveal that the hysteretic spin transition takes place synchronously with the concerted displacive motions of the molecules, representing another rare example including multistep and hysteretic spin transitions due to the synergetic SCO and structural phase transition.

Chiral phonons in microcrystals and nanofibrils of biomolecules

Chiral phonons are concerted mirror-symmetric movements of atomic groups connected by covalent and intermolecular bonds. Such lattice vibrations in crystals of biomolecules should be highly specific to their short- and long-range organizations, but their chiroptical signatures and structure–property relationships remain uncertain. Here we show that terahertz chiroptical spectroscopy enables the registration and attribution of chiral phonons for microscale and nanoscale crystals of amino acids and peptides. Theoretical analysis and computer simulations indicate that sharp mirror-symmetric bands observed for left- and right-handed enantiomers originate from the collective vibrations of biomolecules interconnected by hydrogen bonds into helical chains. The sensitivity of chiral phonons to minute structural changes can be used to identify physical and chemical differences in seemingly identical formulations of dipeptides used in health supplements. The generality of these findings is demonstrated by chiral phonons observed for amyloid nanofibrils of insulin. Their spectral signatures and polarization rotation strongly depend on their maturation stage, which opens a new door for medical applications of terahertz photonics. Chiral phonons—long-range lattice vibrations with rotational motion of atoms—are observed by terahertz chiroptical spectroscopy in biocrystals. Terahertz circular dichroism peaks between 0.2 and 2.0 THz clearly identify the chirality of these phonons in various microcrystalline and nanofibrils of biomolecules.

Role of Ion Distribution and Energy Barriers for Concerted Motion of Subunits in Selectivity Filter Gating of a K+ Channel

Most potassium channels have two main gate locations, hosting an inner gate at the cytosolic entrance and a filter gate in the selectivity filter; the function of these gates is in many channels coupled. To obtain exclusive insights into the molecular mechanisms that determine opening and closing of the filter gate, we use a combination of single-channel recordings and gating analysis in the minimal viral channel KcvNTS. This channel has no inner gate, and its fast closing at negative voltages can therefore be entirely assigned to the filter gate. We find that mutations of S42 in the pore helix severely slow down closing of this filter gate, an effect which is not correlated with hydrogen bond formation by the amino acid at this position. Hence, different from KcsA, which contains the critical E71 in the equivalent position forming a salt bridge, the coupling between selectivity filter and surrounding structures for filter gating must in KcvNTS rely on different modes of interaction. Quantitative analysis of concatemers carrying different numbers of S42T mutations reveals that each subunit contributes the same amount of ∼ 0.4 kcal/mol to the energy barrier for filter closure indicating a concerted action of the subunits. Since the mutations have neither an influence on the unitary current nor on the voltage dependency of the gate, the data stress that the high subunit cooperativity is mediated through conformational changes rather than through changes in the ion occupation in the selectivity filter.

First-principles simulations of Li boracites Li4B7O12Cl and Li5B7O12.5Cl

Lithium boracite crystals have been identified as promising ion conductors for possible use in all-solid-state batteries. With the help of first-principles modeling techniques, we are able to show that these materials have structures with natural interstitial sites which play important roles in Li ion migration processes. The arrangements of these natural interstitial sites follow from group theory analyses of the computed and experimentally analyzed structures. Specifically, the low-temperature $\ensuremath{\alpha}$ phase of ${\mathrm{Li}}_{4}{\mathrm{B}}_{7}{\mathrm{O}}_{12}\mathrm{Cl}$ is computed to have the face-centered rhombohedral $R3c$ structure which is closely related to an ideal face-centered cubic $F\overline{4}3c$ structure with 24 natural interstitial sites per conventional unit cell. Li ion diffusion in this material is found to proceed largely by a concerted motion involving these interstitial sites and two neighboring host lattice sites, consistent with the large measured ionic conductivity of this material. Adding one addition ${\mathrm{Li}}_{2}\mathrm{O}$ cluster per formula unit to ${\mathrm{Li}}_{4}{\mathrm{B}}_{7}{\mathrm{O}}_{12}\mathrm{Cl}$ forms ${\mathrm{Li}}_{5}{\mathrm{B}}_{7}{\mathrm{O}}_{12.5}\mathrm{Cl}$, which crystallizes in the face-centered cubic $F23$ structure, a subgroup of the $F\overline{4}3c$ structure. While these $F23$ crystals have 16 natural interstitial sites per conventional unit cell, their distribution is such that they do not participate in Li ion diffusion mechanisms, as is consistent with the negligible ionic conductivity measured for this material. Phonon spectral analyses of ${\mathrm{Li}}_{4}{\mathrm{B}}_{7}{\mathrm{O}}_{12}\mathrm{Cl}$ in its $R3c$ structure and ${\mathrm{Li}}_{5}{\mathrm{B}}_{7}{\mathrm{O}}_{12.5}\mathrm{Cl}$ in its $F23$ structure show that both crystals are dynamically stable. Chemical stability of these materials is indicated by convex hull analysis of ${\mathrm{Li}}_{4}{\mathrm{B}}_{7}{\mathrm{O}}_{12}\mathrm{Cl}$ and ${\mathrm{Li}}_{5}{\mathrm{B}}_{7}{\mathrm{O}}_{12.5}\mathrm{Cl}$ with respect to their building blocks of LiCl, ${\mathrm{Li}}_{2}\mathrm{O}$, and ${\mathrm{B}}_{2}{\mathrm{O}}_{3}$.

Concerted hinge motions in SARS-CoV-2 spike modulated by glycan-glycan and glycan-lipid interactions

SARS-CoV-2 binds to the host cells through its spike glycoprotein, making it a key target for therapeutic antibodies. The anchoring of the spike to the viral envelope through the stalk domain allows it to function as extended viral antennae for recognition by the host cell surface receptors, and the construction of the complete membrane-bound spike model and description of its dynamics remain the first and most critical steps in understanding the working of this key component of the viral infection machinery.

Opening of KCNQ2 channels does not require concerted movement of all four voltage sensors

In neurons, voltage-gated potassium KCNQ channels (KCNQ2-5) mediate the M-current, one of the major potassium currents throughout the central and peripheral nervous systems. KCNQ channels regulate the resting membrane potential, shape action potentials, and impede repetitive neuronal firing. Inherited mutations in KCNQ2 channel have been linked to the onset of epileptic encephalopathy and other neurodevelopmental disorders. KCNQ2 channels have six transmembrane segments (S1-S6) that form functional tetramers.

“I’m Not a Good Drug Dealer”: Styles of Buprenorphine Diversion in a Multisite Qualitative Study

Background Against the backdrop of the U.S. opioid epidemic, there has been a concerted movement to improve access to buprenorphine maintenance therapy (BMT). In Pennsylvania, where overdose mortality increased 65% between 2015 and 2017, over $75 million has been appropriated toward BMT since 2016. Concurrently, efforts to increase BMT availability while lowering barriers to entry have given way to fears of increased diversion and illegitimate patients. Little is known about the circumstances and motivations that surround buprenorphine diversion, particularly within the context of treatment expansion. Method Drawing on 27 in-depth interviews with individuals who reported sharing or selling buprenorphine in the past year, in this study we consider the relationship between treatment access, treatment experiences, and individuals’ decision to divert buprenorphine, while further comparing motivations for buprenorphine diversion across two Pennsylvania counties with disparate levels of BMT availability. Results We identify four styles of buprenorphine diversion (“ad hoc sellers,” “concerned suppliers,” “social sharers,” “professional dealers”), with different levels of representation by county. Overall, our analysis found the explicit economic exploitation of BMT was rare, while a plurality of participants reported selling unwanted or unneeded buprenorphine only when presented with an opportunity. Conclusions Across our typology, market demand in the form of unmet need for buprenorphine was the major driver of diversion, suggesting that “supply-side interventions” intended to again limit access to BMT may be counterproductive.

Essential Roles of Efferent Duct Multicilia in Male Fertility.

Cilia are microtubule-based hair-like organelles on the cell surface. Cilia have been implicated in various biological processes ranging from mechanosensation to fluid movement. Ciliary dysfunction leads to a plethora of human diseases, known as ciliopathies. Although non-motile primary cilia are ubiquitous, motile multicilia are found in restricted locations of the body, such as the respiratory tract, the oviduct, the efferent duct, and the brain ventricles. Multicilia beat in a whip-like motion to generate fluid flow over the apical surface of an epithelium. The concerted ciliary motion provides the driving force critical for clearing airway mucus and debris, transporting ova from the ovary to the uterus, maintaining sperm in suspension, and circulating cerebrospinal fluid in the brain. In the male reproductive tract, multiciliated cells (MCCs) were first described in the mid-1800s, but their importance in male fertility remained elusive until recently. MCCs exist in the efferent ducts, which are small, highly convoluted tubules that connect the testis to the epididymis and play an essential role in male fertility. In this review, we will introduce multiciliogenesis, discuss mouse models of male infertility with defective multicilia, and summarize our current knowledge on the biological function of multicilia in the male reproductive tract.

Probing Amyloid-DNA Interaction with Nanofluidics.

Nanofluidics is an emerging methodology to investigate single biomacromolecules without functionalization and/or attachment of the molecules to a substrate. In conjunction with fluorescence microscopy, it can be used to investigate structural and dynamical aspects of amyloid-DNA interaction. Here, we summarize the methodology for fabricating lab-on-chip devices in relatively cheap polymer resins and featuring quasi one-dimensional nanochannels with a cross-sectional diameter of tens to a few hundred nanometers. Site-specific staining of amyloid-forming protein Hfq with a fluorescence dye is also described. The methodology is illustrated with two application studies. The first study involves assembling bacterial amyloid proteins such as Hfq on double-stranded DNA and monitoring the folding and compaction of DNA in a condensed state. The second study is about the concerted motion of Hfq on DNA and how this is related to DNA's internal motion. Explicit details of procedures and workflows are given throughout.

Optically Controlled Latching and Launching in Soft Actuators

AbstractSnapping is an abrupt reaction, in which mechanical instability allows the structure to rapidly switch from one stabilized form to another. Snapping is attained through a sudden release of prestored elastic energy. It is perfected by natural species to enhance their preying, locomotion, and reproduction abilities. Recent developments in responsive materials research has allowed the realization of bioinspired snappers and rapidly moving soft robots triggered by external stimuli. However, it remains a grand challenge to reversibly and accurately control the snapping dynamics in terms of, e.g., onset timing and speed of motion. Here, a facile method to obtain light‐fueled snapping‐like launching with precise control over the elastic energy released and the onset timing is reported. The elastic energy is prestored in a light‐responsive liquid crystal elastomer actuator, and the launching event is dictated by releasing the energy through a photothermally induced crystal‐to‐liquid transition of a liquid‐crystalline adhesive latch. The method provides manual control over the amount of prestored energy, motion speed upon multiple launching events, and enables demonstrations such as jumping and catapult motions in soft robots and concerted motions of multiple launchers. The results provide a practical solution for controlled fast motions in soft small‐scale robotics.

Exhibiting environment sensitive optical properties through multiscale modelling: A study of photoactivatable probes

To assess a tumor biomarker like the cyclooxygenase-2 enzyme (COX-2), non-invasive imaging techniques are powerful tools. The (non-) linear optical properties of activatable fluorescent probes which are selectively bound to the biomarker can therefore be exploited. The here presented molecular modelling results based on multi-scale modelling techniques highlight the importance of the conformational versatility and of changes in the electronic interactions of such probes when they are embedded in water or in the COX-2 homodimer enzyme. The ANQ-IMC-6 probe, which combines the binding domain/scaffold of indomethacin (IMC) on COX-2 with the optical properties of acenaphtho[1,2-b]quinoxaline (ANQ), is found to be folded in the solvent and unfolded in the enzyme. A concerted movement of the probe and the protein is seen, while the rotational autocorrelation function exhibits also the intrinsic properties of the probe. Hybrid Quantum Mechanics/Molecular Mechanics (QM/MM) calculations are used to simulate the one-photon and two-photon absorption spectra along with the first hyperpolarizability. The transition has a local character in vacuum, but changes to a charge transfer one in the presence of the microenvironment of the enzyme. This is also visible through a change of the shape of the absorption spectrum, while at the same time the simulated signals of second harmonic generation experiments are strongly enhanced. The results of this work prove that an environment sensitive probe with an anchoring group and an optical active part can be constructed for use in absorption spectroscopy, without the need to revert to fluorescence experiments.

Concerted Motions and Molecular Function: What Physical Chemistry We Can Learn from Light-Driven Ion-Pumping Rhodopsins.

Transmembrane ion gradients are generated and maintained by ion-pumping proteins in cells. Light-driven ion-pumping rhodopsins are retinal-containing proteins found in archaea, bacteria, and eukarya. Photoisomerization of the retinal chromophore induces structural changes in the protein, allowing the transport of ions in a particular direction. Understanding unidirectional ion transport by ion-pumping rhodopsins is an exciting challenge for biophysical chemistry. Concerted changes in ion-binding affinities of the ion-binding sites in proteins are key to unidirectional ion transport, as is the coupling between the chromophore and the protein moiety to drive the concerted motions regulating ion-binding affinities. The commonality of ion-pumping rhodopsin protein structures and the diversity of their ion-pumping functions suggest universal principles governing ion transport, which would be widely applicable to molecular systems. In this Perspective, I review the insights obtained from previous studies on rhodopsins and discuss future perspectives.

The Interrelationships between Metacognition and Modeling Competency: The Moderating Role of the Academic Year

<p style="text-align:justify">Several concerted movements toward mathematical modeling have been seen in the last decade, reflecting the growing global relationship between the role of mathematics in the context of modern science, technology and real life. The literature has mainly covered the theoretical basis of research questions in mathematical modeling and the use of effective research methods in the studies. Driven by the Realistic Mathematics Education (RME) theory and empirical evidence on metacognition and modeling competency, this research aimed at exploring the interrelationships between metacognition and mathematical modeling and academic year level as a moderator via the SEM approach. This study involved 538 students as participants. From this sample, 133 students (24.7%) were from the first academic year, 223 (41.4%) were from the second and 182 (33.8%) were from the third. A correlational research design was employed to answer the research question. Cluster random sampling was used to gather the sample. We employed structural equation modeling (SEM) to test the hypothesized moderation employing IBM SPSS Amos version 18. Our findings confirmed the direct correlation between metacognition and mathematical modeling was statistically significant. Academic year level as a partial moderator significantly moderates the interrelationships between the metacognitive strategies and mathematical modeling competency. The effect of metacognition on mathematical modeling competency was more pronounced in the year two group compared to the year one and three groups.</p>

Universal Properties and Specificities of the β2-Adrenergic Receptor-Gs Protein Complex Activation Mechanism Revealed by All-Atom Molecular Dynamics Simulations.

G protein-coupled receptors (GPCRs) are transmembrane proteins of high pharmacological relevance. It has been proposed that their activity is linked to structurally distinct, dynamically interconverting functional states and the process of activation relies on an interconnecting network of conformational switches in the transmembrane domain. However, it is yet to be uncovered how ligands with different extents of functional effect exert their actions. According to our recent hypothesis, based on indirect observations and the literature data, the transmission of the external stimulus to the intracellular surface is accompanied by the shift of macroscopic polarization in the transmembrane domain, furnished by concerted movements of highly conserved polar motifs and the rearrangement of polar species. In this follow-up study, we have examined the β2-adrenergic receptor (β2AR) to see if our hypothesis drawn from an extensive study of the μ-opioid receptor (MOP) is fundamental and directly transferable to other class A GPCRs. We have found that there are some general similarities between the two receptors, in agreement with previous studies, and there are some receptor-specific differences that could be associated with different signaling pathways.

Structural variability and concerted motions of the T cell receptor - CD3 complex.

We investigate the structural and orientational variability of the membrane-embedded T cell receptor (TCR) - CD3 complex in extensive atomistic molecular dynamics simulations based on the recent cryo-EM structure determined by Dong et al., 2019. We find that the TCR extracellular (EC) domain is highly variable in its orientation by attaining tilt angles relative to the membrane normal that range from 15° to 55°. The tilt angle of the TCR EC domain is both coupled to a rotation of the domain and to characteristic changes throughout the TCR - CD3 complex, in particular in the EC interactions of the Cβ FG loop of the TCR, as well as in the orientation of transmembrane helices. The concerted motions of the membrane-embedded TCR - CD3 complex revealed in our simulations provide atomistic insights on conformational changes of the complex in response to tilt-inducing forces on antigen-bound TCRs.

Concerted conformational dynamics and water movements in the ghrelin G protein-coupled receptor.

There is increasing support for water molecules playing a role in signal propagation through G protein-coupled receptors (GPCRs). However, exploration of the hydration features of GPCRs is still in its infancy. Here, we combined site-specific labeling with unnatural amino acids to molecular dynamics to delineate how local hydration of the ghrelin receptor growth hormone secretagogue receptor (GHSR) is rearranged upon activation. We found that GHSR is characterized by a specific hydration pattern that is selectively remodeled by pharmacologically distinct ligands and by the lipid environment. This process is directly related to the concerted movements of the transmembrane domains of the receptor. These results demonstrate that the conformational dynamics of GHSR are tightly coupled to the movements of internal water molecules, further enhancing our understanding of the molecular bases of GPCR-mediated signaling.

In situ motions of individual inner-hair-cell stereocilia from stapes stimulation in adult mice

In vertebrate hearing organs, mechanical vibrations are converted to ionic currents through mechanoelectrical-transduction (MET) channels. Concerted stereocilia motion produces an ensemble MET current driving the hair-cell receptor potential. Mammalian cochleae are unique in that the tuning of sensory cells is determined by their mechanical environment and the mode of hair-bundle stimulation that their environment creates. However, little is known about the in situ intra-hair-bundle motions of stereocilia relative to one another, or to their environment. In this study, high-speed imaging allowed the stereocilium and cell-body motions of inner hair cells to be monitored in an ex vivo organ of Corti (OoC) mouse preparation. We have found that the OoC rotates about the base of the inner pillar cell, the hair bundle rotates about its base and lags behind the motion of the apical surface of the cell, and the individual stereocilia move semi-independently within a given hair bundle.

Atomistic dynamics of elimination and nucleophilic substitution disentangled for the F- + CH3CH2Cl reaction.

Chemical reaction dynamics are studied to follow and understand the concerted motion of several atoms while they rearrange from reactants to products. With the number of atoms growing, the number of pathways, transition states, and product channels also increases and rapidly presents a challenge to experiment and theory. Here, we disentangle the competition between bimolecular nucleophilic substitution (SN2) and base-induced elimination (E2) in the polyatomic reaction F- + CH3 CH2 Cl. We find quantitative agreement for the energy- and angle-differential reactive scattering cross sections between ion imaging experiments and quasi-classical trajectory simulations on a 21-dimensional potential energy hypersurface. The anti-E2 pathway is most important, but the SN2 pathway becomes more relevant as the collision energy is increased. In both cases the reaction is dominated by direct dynamics. Our study presents atomic level dynamics of a major benchmark reaction in physical organic chemistry, thereby pushing the number of atoms for detailed reaction dynamics studies to a size that allows applications in many areas of complex chemical networks and environments.

Phase transition of two-dimensional ferroelectric and paraelectric Ga2O3 monolayers: A density functional theory and machine learning study

Ga2O3 is a wide-band-gap semiconductor of great interest for applications in electronics and optoelectronics. Two-dimensional (2D) Ga2O3 synthesized from top-down or bottom-up processes can reveal brand new heterogeneous structures and promising applications. In this paper, we study phase transitions among three low-energy stable Ga2O3 monolayer configurations using density functional theory and a newly developed machine-learning Gaussian approximation potential, together with solid-state nudged elastic band calculations. Kinetic minimum energy paths involving direct atomic jump as well as concerted layer motion are investigated. The low phase transition barriers indicate feasible tunability of the phase transition and orientation via strain engineering and external electric fields. Large-scale calculations using the newly trained machine-learning potential on the thermally activated single-atom jumps reveal the clear nucleation and growth processes of different domains. The results provide useful insights to future experimental synthesis and characterization of 2D Ga2O3 monolayers.

Static investigation of the small clusters on the Cu(111) and Au(111) surfaces

The diffusion properties of small clusters Agn, Cun, and Aun on the Cu(111) and Au(111) surfaces were studied using the molecular statics (MS) in order to understand the atomistic processes underlying the motion. In this work, the atomic interaction potential is modeled by a semi-empirical Embedded Atom Method (EAM), while the drag method is used to determine the static activation energy for each diffusion path. The presented results indicate that the dimer can diffuse on the (111) surface via the zig-zag and concerted motion mechanisms. The trimer diffuses according to the concerted motion mechanism. For the tetramer diffusion, the mechanism that consumes the least amount of energy is the zig-zag motion, in which only two atoms are needed for the diffusion process at one time. This allows finding a static activation energy smaller compared to the trimer diffusion.