Static Structures Research Articles

Atomic-Level View of the Functional Transition in Vertebrate Hemoglobins: The Case of Antarctic Fish Hbs.

Tetrameric hemoglobins (Hbs) are prototypal systems for studies aimed at unveiling basic structure–function relationships as well as investigating the molecular/structural basis of adaptation of living organisms to extreme conditions. However, a chronological analysis of decade-long studies conducted on Hbs is illuminating on the difficulties associated with the attempts of gaining functional insights from static structures. Here, we applied molecular dynamics (MD) simulations to explore the functional transition from the T to the R state of the hemoglobin of the Antarctic fish Trematomus bernacchii (HbTb). Our study clearly demonstrates the ability of the MD technique to accurately describe the transition of HbTb from the T to R-like states, as shown by a number of global and local structural indicators. A comparative analysis of the structural states that HbTb assumes in the simulations with those detected in previous MD analyses conducted on HbA (human Hb) highlights interesting analogies (similarity of the transition pathway) and differences (distinct population of intermediate states). In particular, the ability of HbTb to significantly populate intermediate states along the functional pathway explains the observed propensity of this protein to assume these structures in the crystalline state. It also explains some functional data reported on the protein that indicate the occurrence of other functional states in addition to the canonical R and T ones. These findings are in line with the emerging idea that the classical two-state view underlying tetrameric Hb functionality is probably an oversimplification and that other structural states play important roles in these proteins. The ability of MD simulations to accurately describe the functional pathway in tetrameric Hbs suggests that this approach may be effectively applied to unravel the molecular and structural basis of Hbs exhibiting peculiar functional properties as a consequence of the environmental adaptation of the host organism.

Molecular Uniting Set Identified Characteristic (MUSIC) of Organic Optoelectronic Material

Comprehensive SummaryResearchers investigated the organic optoelectronic materials and facilitated their development in organic light‐emitting diodes (OLEDs), chemo‐ and biosensors, organic solar cells, data storage, and anticounterfeiting devices. Atoms make up molecules through chemical bonds, and molecular aggregates are formed through weak intermolecular interactions. The opto‐electronic performance of these materials depends on not only the properties of the well‐designed molecules with specific function groups, but also their aggregate states. The molecular aggregates in the form of nanoparticles can be applied in biological imaging, and films can be applied to photovoltaic and photodeformable devices, in which, the alignment of optoelectronic molecules can be either an ordered crystalline or an amorphous state. Generally, the crystalline materials could be deeply investigated by single crystal/powder X‐ray diffraction analysis, which could provide the accurate information about molecular conformations, interactions and packing characteristics. It afforded a convenient way to investigate the possible relationship between molecular aggregates and opto‐electronic properties. Among various opto‐electronic materials, organic room temperature phosphorescence (RTP) materials exhibit the extremely sensitive luminescence property to molecular aggregates, even the dynamic properties can be detected by the tiny change of molecular aggregates. Thus, we selected the organic RTP emission as the output information of molecular aggregates, and afforded typical examples to find the possible relation between RTP effect and molecular packing. Accordingly, molecular packing can be adjusted by the external force as light, mechanical force, temperature, electric field, and so on, as well as the molecular structures as the building blocks, and the systematic investigation in the dynamic and static aggregation structures is of great value to the design of various optoelectronic materials. This review discusses the relationship among molecular structures, aggregation behaviors and corresponding optoelectronic properties by a comprehensive summary of recent research in our group, and the concept of molecular uniting set identified characteristic (MUSIC) is afforded. What is the most favorite and original chemistry developed in your research group?The concept of “Suitable Isolation Group” for molecular design of organic second‐order nonlinear optical (NLO) materials. Molecular packing is highlighted as the key point to opto‐electronic materials, which are partially summarized in this mini review to present “MUSIC” in the molecular world.How do you supervise your students?Discussions. We do discussions for science, interests and other topics related to research together, through which to solve the encountered problems.What is the most important personality for scientific research?Curiosity, desire to advance, persistence, sense of urgency, and teamspirit.What are your hobbies? What's your favorite book(s)??Listening to music and reading books, and my favorite book is “Tao Te Ching (道德经)”.Could you please give us some advices on improving Chinese Journal of Chemistry?There are many different approaches to improve CJC, perhaps, to attract and publish good papers is the key, especially those from Chinese authors since the chemistry in China develops rapidly.If you have anything else to tell our readers, please feel free to do so?While pursuing new published exciting papers, it is a very good habit to read related old excellent literatures and the classics.

Relationship between feeding development and alterations in orofacial motor skills

Introduction: The orofacial system is an anatomical-functional unit that enables the human being to perform various functions essential for life. It consists of oral structures, static and dynamic structures, and its harmonious functioning is based on the balanced relationship between its parts. Method: A systematic review was carried out to find out the relationship between feeding development and orofacial motor disturbances. As a search strategy, equations were formulated with selected descriptors MESH and DECS (“feeding, infancy”, “orofacial motricity”, “phonoaudiology”, “pediatrics”), the databases consulted were Pubmed, Science Direct, Scopus, Redalyc, Dialnet, Scielo, Proquest, World wide science, Biomed Central, Red Iberoamericana de Innovación y Conocimiento Científico, Semantic Scholar, Revista Javeriana.

Structural study of Li2S-GeS2 glasses: Ge[sbnd]S network and local environment of Li

The static structures of (Li2S)x(GeS2)100-x glasses (x = 0, 20, 30, 40 and 50) were investigated by using a combination of diffraction measurements and simulation techniques. The X-ray diffraction results show that the host GeS network is formed by linkages of GeS4 tetrahedra. The three-dimensional structure models of GeS network were generated by using the X-ray diffraction data and reverse Monte Carlo (RMC) simulation. The RMC models show that the number of edge-sharing GeS4 tetrahedra decreases as Li2S content but its ratio to the number of connections between GeS4 tetrahedra remains substantially constant irrespective of the composition. The Li ion sites in the GeS network structures were determined by molecular dynamics (MD) simulation with reference to the previously reported neutron diffraction data. The MD results show that each Li ion is located in a deformed octahedral site consisting of bridging and non-bridging sulphur atoms.

Decapod-inspired pigment modulation for active building facades

Typical buildings are static structures, unable to adjust to dynamic temperature and daylight fluctuations. Adaptive facades that are responsive to these unsteady solar conditions can substantially reduce operational energy inefficiencies, indoor heating, cooling, and lighting costs, as well as greenhouse-gas emissions. Inspired by marine organisms that disperse pigments within their skin, we propose an adaptive building interface that uses reversible fluid injections to tune optical transmission. Pigmented fluids with tunable morphologies are reversibly injected and withdrawn from confined layers, achieving locally-adjustable shading and interior solar exposure. Multicell arrays tiled across large areas enable differential and dynamic building responses, demonstrated using both experimental and simulated approaches. Fluidic reconfigurations can find optimal states over time to reduce heating, cooling, and lighting energy in our models by over 30% compared to current available electrochromic technologies.

Aspect Oriented Programming: Trends and Applications

The competitive advantage of aspect oriented programming (AOP) is that it improves the maintainability and understandability of software systems by modularizing crosscutting concerns. However, some concerns, such as logging or debugging, may be overlooked and should be entangled and distributed across the code base. AOP is a software development paradigm that enables developers to capture crosscutting concerns in split-aspect modes. Additionally, it is a novel notion that has the potential to improve the quality of software programs by removing the complexity involved with the production of code tangles via the usage of separation of concerns. As a result, it provides more modularity. Throughout its early development, some believed that AOP was easier to build and maintain than other implementations since it was based on an existing one. The statements are predicated on the premise that local improvements are easier to implement. Additionally, without appropriate visualization tools for both static and dynamic structures, cross-cutting challenges may be difficult for developers and researchers to appreciate. In recent years, AspectJ has begun to enable the depiction of crosscutting concerns via the release of IDE plugins. This article explains aspect oriented programming and how it may be used to improve the readability and maintainability of software projects. Additionally, it will evaluate the challenges it presents to application developers and academics.

Chiral separation of rotating robots through obstacle arrays

The interplay between active matter and environmental complexity can be applied to achieve complex functions ranging from rectification, separation, and capture to sorting of active particles. Here, we experimentally realize chiral separation of disk-shaped active rotors by using the interactions between the rotors and the obstacle array. Differently chiral active particles passing through the obstacle array exhibit opposite lateral drifts. The separation efficiency is excellent provided that the obstacle array is of sufficient length. The spin and longitudinal flow of the rotors and the friction between rotors and obstacles jointly determine the lateral drift of the rotors, thus leading to chiral separation. Furthermore, we propose a simple theoretical model, which captures the essential mechanism underlying the chiral separation and properly reproduces the experimental critical collision angle. This scheme could separate objects with static chiral structures, once an external source can power the objects to spin with different angular velocities.

Exploration of Somatostatin Binding Mechanism to Somatostatin Receptor Subtype 4.

Somatostatin (also named as growth hormone-inhibiting hormone or somatotropin release-inhibiting factor) is a regulatory peptide important for the proper functioning of the endocrine system, local inflammatory reactions, mood and motor coordination, and behavioral responses to stress. Somatostatin exerts its effects via binding to G-protein-coupled somatostatin receptors of which the fourth subtype (SSTR4) is a particularly important receptor mediating analgesic, anti-inflammatory, and anti-depressant effects without endocrine actions. Thus, SSTR4 agonists are promising drug candidates. Although the knowledge of the atomic resolution-binding modes of SST would be essential for drug development, experimental elucidation of the structures of SSTR4 and its complexes is still awaiting. In the present study, structures of the somatostatin–SSTR4 complex were produced using an unbiased, blind docking approach. Beyond the static structures, the binding mechanism of SST was also elucidated in the explicit water molecular dynamics (MD) calculations, and key binding modes (external, intermediate, and internal) were distinguished. The most important residues on both receptor and SST sides were identified. An energetic comparison of SST binding to SSTR4 and 2 offered a residue-level explanation of receptor subtype selectivity. The calculated structures show good agreement with available experimental results and indicate that somatostatin binding is realized via prerequisite binding modes and an induced fit mechanism. The identified binding modes and the corresponding key residues provide useful information for future drug design targeting SSTR4.

Experimental study on dynamic and static structure establishment and recovery rate of fresh cement paste by composite thickening agents

The rheological and thixotropic properties, as well as the establishment of dynamic and static structures effectively reflect the workability of the cement paste. In order to investigate the effects of organic and inorganic composite thickening agents on fresh cement paste, the rheological curves, structural recovery rate, storage modulus G′ and loss modulus G″ of cement pastes mixed with limestone powder (LP), re-dispersible polymer powder (RPP) and hydroxypropyl methyl cellulose ether (HPMC) were tested by Anton Paar MCR 102 rotary rheometer. The results showed that LP and RPP reduced the yield stress and enhanced workability, and LP also improved the establishment of static structures. The incorporation of HPMC facilitated the recovery rate of static structure, and obviously improved the deformation resistance of the cement paste by reducing the difference between the G′ and the G″. However, a single thickening agent was hard to balance the rheological parameters of the pastes. While the combination of LP, RPP and HPMC could improve the rate of structure establishment and recovery, and increase the deformation resistance as well as the stability of the paste. The dense filling effect of LP, the film-forming and bridging effect of RPP, and the winding and water retention effects of HPMC together made up the synergistic effect to further improve the stability of the pastes.

Computational Study for Amino Acid Production from Carboxylic Acid via 14C β-decay

To study the chemical origin of life, we investigated the amino acid production probability from radiocarbon (C-14)-containing carboxylic acid via beta-decay using a newly developed Monte Carlo simulator for molecular dynamics calculation. Using the simulation, we calculated the dynamical trajectory of N-14 recoiled via C-14 beta-decay in [3-C-14]propionic acid and evaluated the staying probability of N-14 in the compound, which is the glycinium (a protonated glycine) production probability from [3-C-14]propionic acid. The glycinium production probability was calculated to be 78.7% assuming static compound structures of [3-C-14]propionic acid and a glycinium C-N binding potential energy of 3.93 eV. From calculations with various binding potential parameters, a glycinium production probability of approximately 30% was expected by simulation in case of a loose C-N binding potential energy of 2-eV.

Ionic Conduction Mechanism and Design of Metal-Organic Framework Based Quasi-Solid-State Electrolytes.

We report the theoretical and experimental investigation of two polyoxometalate-based metal–organic frameworks (MOFs), [(MnMo6)2(TFPM)]imine and [(AlMo6)2(TFPM)]imine, as quasi-solid-state electrolytes. Classical molecular dynamics coupled with quantum chemistry and grand canonical Monte Carlo are utilized to model the corresponding diffusion and ionic conduction in the two materials. Using different approximate levels of ion diffusion behavior, the primary ionic conduction mechanism was identified as solvent-assisted hopping (>77%). Detailed static and dynamic solvation structures were obtained to interpret Li+ motion with high spatial and temporal resolution. A rationally designed noninterpenetrating MOF-688(one-fold) material is proposed to achieve 6–8 times better performance (1.6–1.7 mS cm–1) than the current state-of-the-art (0.19–0.35 mS cm–1).

An Alpha Finite Element Method for Linear Static and Buckling Analysis of Textile-Like Sheet Materials

A four node isoparametric shell element (Q4) based on Mindlin/Reissner plate theory and the alpha finite element method (αFEM) was formulated for a nearly exact solution of linear static and buckling analysis of textile-like sheet material. The novel idea of αFEM-Q4 is assumed to be similar to the framework of conventional finite element approaches for Q4, but the gradient of strains is scaled by a factor α ∈ [0, 1]. The numerical examples demonstrate that the αFEM-Q4 can improve the accuracy of FEM solution in static and buckling analysis shell structures of non-woven fabric. However, the αFEM-Q4 cannot provide the nearly exact solution to all elasticity problems. In addition, it also requires a quadrilateral mesh that cannot be fully generated by common geometric algorithms for complicated problem domains.

Allosteric couplings upon binding of RfaH to transcription elongation complexes.

In every domain of life, NusG-like proteins bind to the elongating RNA polymerase (RNAP) to support processive RNA synthesis and to couple transcription to ongoing cellular processes. Structures of factor-bound transcription elongation complexes (TECs) reveal similar contacts to RNAP, consistent with a shared mechanism of action. However, NusG homologs differ in their regulatory roles, modes of recruitment, and effects on RNA synthesis. Some of these differences could be due to conformational changes in RNAP and NusG-like proteins, which cannot be captured in static structures. Here, we employed hydrogen-deuterium exchange mass spectrometry to investigate changes in local and non-local structural dynamics of Escherichia coli NusG and its paralog RfaH, which have opposite effects on expression of xenogenes, upon binding to TEC. We found that NusG and RfaH regions that bind RNAP became solvent-protected in factor-bound TECs, whereas RNAP regions that interact with both factors showed opposite deuterium uptake changes when bound to NusG or RfaH. Additional changes far from the factor-binding site were observed only with RfaH. Our results provide insights into differences in structural dynamics exerted by NusG and RfaH during binding to TEC, which may explain their different functional outcomes and allosteric regulation of transcriptional pausing by RfaH.

Heterogeneous interactions and polymer entropy decide organization and dynamics of chromatin domains

Chromatin is known to be organized into multiple domains of varying sizes and compaction. While these domains are often imagined as static structures, they are highly dynamic and show cell-to-cell variability. Since processes such as gene regulation and DNA replication occur in the context of these domains, it is important to understand their organization, fluctuation, and dynamics. To simulate chromatin domains, one requires knowledge of interaction strengths among chromatin segments. Here, we derive interaction-strength parameters from experimentally known contact maps and use them to predict chromatin organization and dynamics. Taking two domains on the human chromosome as examples, we investigate its three-dimensional organization, size/shape fluctuations, and dynamics of different segments within a domain, accounting for hydrodynamic effects. Considering different cell types, we quantify changes in interaction strengths and chromatin shape fluctuations in different epigenetic states. Perturbing the interaction strengths systematically, we further investigate how epigenetic-like changes can alter the spatio-temporal nature of the domains. Our results show that heterogeneous weak interactions are crucial in determining the organization of the domains. Computing effective stiffness and relaxation times, we investigate how perturbations in interactions affect the solid- and liquid-like nature of chromatin domains. Quantifying dynamics of chromatin segments within a domain, we show how the competition between polymer entropy and interaction energy influence the timescales of loop formation and maintenance of stable loops.

Effect of Ligands and Transducers on the Neurotensin Receptor 1 Conformational Ensemble.

Using a discrete, intracellular 19F nuclear magnetic resonance (NMR) probe on transmembrane helix 6 of the neurotensin receptor 1 (NTS1), we aim to understand how ligands and transducers modulate the receptor's structural ensemble in a solution. For apo NTS1, 19F NMR spectra reveal an ensemble of at least three conformational substates (one inactive and two active-like) in equilibrium that exchange on the millisecond to second timescale. Dynamic NMR experiments reveal that these substates follow a linear three-site exchange process that is both thermodynamically and kinetically remodeled by orthosteric ligands. As previously observed in other G protein-coupled receptors (GPCRs), the full agonist is insufficient to completely stabilize the active-like state. The inactive substate is abolished upon coupling to β-arrestin-1 (βArr1) or the C-terminal helix of Gαq, which comprises ≳60% of the GPCR/G protein interface surface area. Whereas βArr1 exclusively selects for pre-existing active-like substates, the Gαq peptide induces a new substate. Both transducer molecules promote substantial line broadening of active-like states, suggesting contributions from additional microsecond to millisecond exchange processes. Together, our study suggests that (i) the NTS1 allosteric activation mechanism may be alternatively dominated by induced fit or conformational selection depending on the coupled transducer, and (ii) the available static structures do not represent the entire conformational ensemble observed in a solution.

A static and dynamic copula-based ARIMA-fGARCH approach to determinants of carbon dioxide emissions in Argentina.

This paper attempts to model both static and dynamic dependence structures and measure impacts of energy consumptions (both renewable (EC) and non-renewable (REN) energies), economic globalization (GLO), and economic growth (GDP) on carbon dioxide (CO2) emissions in Argentina over the period 1970-2020. For analyses purpose, the current research deploys the novel static and dynamic copula-based ARIMA-fGARCH with different submodels. The static bivariate copula results show that the growth rates of the pairs EC-CO2 and GDP-CO2 are asymmetrically positive co-movements and have high left tail (extreme) dependencies, implying that the increase in non-renewable energy and economic growth can critically contribute to the environmental degradation, and the decrease in the consumption of non-renewable energy at a high level will consequently reduce the CO2 emissions at the same level. Based on several copula-based dependence measures, we document that between the two factors, the non-renewable energy has a stronger impact than the economic growth regarding the CO2 emissions. On the other hand, the growth rates of both economic globalization and renewable energy symmetrically negatively co-move with the growth rates of the CO2 emissions, but they have no extreme dependencies, indicating that these factors contribute to Argentina's environmental quality, in which the factor of renewable energy has a greater impact. Furthermore, the dynamic copula outcomes show that the (tail) dependencies of CO2 emissions on the non-renewable energy and economic growth are time-varying, while the pairs REN-CO2 and GLO-CO2 possess only dynamic dependencies, but no dynamic tail dependencies. Moreover, through the dynamic copula-based dependence, the environmental Kuznets curve (EKC) hypothesis can be estimated and illustrated explicitly. In addition, we leverage multivariate vine copulas for modelling dependence structures of the five variables simultaneously, which can reveal rich information regarding conditional associations among the relevant variables. Some policy implications are also provided to mitigate CO2 emissions.

Bringing chemical structures to life with augmented reality, machine learning, and quantum chemistry.

Visualizing 3D molecular structures is crucial to understanding and predicting their chemical behavior. However, static 2D hand-drawn skeletal structures remain the preferred method of chemical communication. Here, we combine cutting-edge technologies in augmented reality (AR), machine learning, and computational chemistry to develop MolAR, an open-source mobile application for visualizing molecules in AR directly from their hand-drawn chemical structures. Users can also visualize any molecule or protein directly from its name or protein data bank ID and compute chemical properties in real time via quantum chemistry cloud computing. MolAR provides an easily accessible platform for the scientific community to visualize and interact with 3D molecular structures in an immersive and engaging way.

Phonon transport properties of particulate physical gels.

Particulate physical gels are sparse, low-density amorphous materials in which clusters of glasses are connected to form a heterogeneous network structure. This structure is characterized by two length scales, ξs and ξG: ξs measures the length of heterogeneities in the network structure and ξG is the size of glassy clusters. Accordingly, the vibrational states (eigenmodes) of such a material also exhibit a multiscale nature with two characteristic frequencies, ω* and ωG, which are associated with ξs and ξG, respectively: (i) phonon-like vibrations in the homogeneous medium at ω<ω*, (ii) phonon-like vibrations in the heterogeneous medium at ω*<ω<ωG, and (iii) disordered vibrations in the glassy clusters at ω > ωG. Here, we demonstrate that the multiscale characteristics seen in the static structures and vibrational states also extend to the phonon transport properties. Phonon transport exhibits two distinct crossovers at frequencies ω* and ωG (or at wavenumbers of ∼ξs -1 and ∼ξG -1). In particular, both transverse and longitudinal phonons cross over between Rayleigh scattering at ω<ω* and diffusive damping at ω>ω*. Remarkably, the Ioffe-Regel limit is located at the very low frequency of ω*. Thus, phonon transport is localized above ω*, even where phonon-like vibrational states persist. This markedly strong scattering behavior is caused by the sparse, porous structure of the gel.

Quantification of the heterogeneous effect of static and dynamic perivascular structures on patient-specific local aortic wall mechanics using inverse finite element modeling and DENSE MRI

Recent studies have highlighted the relevance of perivascular interactions on aortic wall mechanics. Most of the approaches assume static perivascular structures; however, the beating heart dynamically displaces the neighboring aorta. We develop a model to account for the effect of periaortic interactions due to static and dynamic structures by prescribing a moving elastic foundation boundary condition (EFBC) embedded into an inverse finite element algorithm using in vivo displacements from 2D displacement encoding with stimulated echoes (DENSE) MRI as target data. We applied this method at three different locations of interest, the distal aortic arch (DAA), descending thoracic aorta (DTA), and infrarenal abdominal aorta (IAA) for a total of 27 cases in healthy humans. The model reproduces the target diastole-to-systole deformation and bulk displacement of the aortic wall with median displacement errors below 0.5mm. The EFBC showed good agreement with the location of anatomical features and was consistent among individuals of similar characteristics. Results show that an energy source acting on the adventitia is required to reproduce the displacements measured at the vicinity of the heart, but not at the abdomen. The average adventitial load as a percentage of the luminal pulse-pressure was found to increase with age and to decrease along the descending aorta, from 61% at the DAA to 37% at the DTA, and 30% at the IAA. This approach offers a patient-specific method to estimate in vivo adventitial loads and aortic wall stiffness, which can bring a better understanding of normal and pathological in vivo aortic function.

Unexpected Dynamic Binding May Rescue the Binding Affinity of Rivaroxaban in a Mutant of Coagulation Factor X.

A novel coagulation factor X (FX) Tyr319Cys mutation (Y99C as chymotrypsin numbering) was identified in a patient with severe bleeding. Unlike the earlier reported Y99A mutant, this mutant can bind and cleave its specific chromogenetic substrate at a normal level, suggesting an intact binding pocket. Here, using molecular dynamics simulations and MM-PBSA calculations on a FX-rivaroxaban (RIV) complex, we confirmed a much stronger binding of RIV in Y99C than in Y99A on a molecular level, which is actually the average result of multiple binding poses in dynamics. Detailed structural analyses also indicated the moderate flexibility of the 99-loop and the importance of the flexible side chain of Trp215 in the different binding poses. This case again emphasizes that binding of ligands may not only be a dynamic process but also a dynamic state, which is often neglected in drug design and screening based on static X-ray structures. In addition, the computational results somewhat confirmed our hypothesis on the activated Tyr319Cys FX (Y99C FXa) with an impaired procoagulant function to bind inhibitors of FXa and to be developed into a potential reversal agent for novel oral anticoagulants (NOAC).