Computational Structural Analysis Research Articles

Rare variant burden analysis from exomes of three consanguineous families reveals LILRB1 and PRSS3 as potential key proteins in inflammatory bowel disease pathogenesis.

Inflammatory bowel disease (IBD) is a chronic autoimmune disorder characterized by severe inflammation and mucosal destruction of the intestine. The specific, complex molecular processes underlying IBD pathogenesis are not well understood. Therefore, this study is aimed at identifying and uncovering the role of key genetic factors in IBD. The whole exome sequences (WESs) of three consanguineous Saudi families having many siblings with IBD were analyzed to discover the causal genetic defect. Then, we used a combination of artificial intelligence approaches, such as functional enrichment analysis using immune pathways and a set of computational functional validation tools for gene expression, immune cell expression analyses, phenotype aggregation, and the system biology of innate immunity, to highlight potential IBD genes that play an important role in its pathobiology. Our findings have shown a causal group of extremely rare variants in the LILRB1 (Q53L, Y99N, W351G, D365A, and Q376H) and PRSS3 (F4L and V25I) genes in IBD-affected siblings. Findings from amino acids in conserved domains, tertiary-level structural deviations, and stability analysis have confirmed that these variants have a negative impact on structural features in the corresponding proteins. Intensive computational structural analysis shows that both genes have very high expression in the gastrointestinal tract and immune organs and are involved in a variety of innate immune system pathways. Since the innate immune system detects microbial infections, any defect in this system could lead to immune functional impairment contributing to IBD. The present study proposes a novel strategy for unraveling the complex genetic architecture of IBD by integrating WES data of familial cases, with computational analysis.

Computational analysis of structure manufactured by means of the steel framing system. Case study: industrial warehouse

A study is carried out between the traditional system of industrial warehouse construction, which is characterized using hot-rolled steel profiles, in comparison with the Steel Framing system, which uses low-thickness cold-formed steel profiles. Although the low-thickness profiles used in Steel Framing may generate mistrust, these profiles work by shape and not by mass. Steel Framing being a modern system, in our region it is not easy to find industrial warehouse constructed with low-thickness cold-formed steel profiles for the main and secondary elements, so this study not only focuses on the constructive aspects, but also contributes to understand the physical response of the Steel Framing system to different loads. Between the two mentioned systems, the seismic-resistant design of the industrial structure is also included to first check if it is possible to use the Steel Framing system in medium industrial warehouse, located in highly seismic areas, such as the coastal region of Ecuador. It has been proven that the Steel Framing system is resistant to high winds, earthquakes and other loads that are established in national and international regulations, and we proved that taking advantage of the effective properties of cold-formed profiles increases their resistance The results of drifts demonstrate the seismic resistance of the system, with the value of 0.00107 being the maximum value of inelastic drift obtained in the X direction, which represents only 5.37% of the value allowed in the standard.

Structural and Pathogenic Impacts of ABCA4 Variants in Retinal Degenerations-An In-Silico Study.

The retina-specific ATP-binding cassette transporter protein ABCA4 is responsible for properly continuing the visual cycle by removing toxic retinoid byproducts of phototransduction. Functional impairment caused by ABCA4 sequence variations is the leading cause of autosomal recessive inherited retinal disorders, including Stargardt disease, retinitis pigmentosa, and cone-rod dystrophy. To date, more than 3000 ABCA4 genetic variants have been identified, approximately 40 percent of which have not been able to be classified for pathogenicity assessments. This study examined 30 missense ABCA4 variants using AlphaFold2 protein modeling and computational structure analysis for pathogenicity prediction. All variants classified as pathogenic (n = 10) were found to have deleterious structural consequences. Eight of the ten benign variants were structurally neutral, while the remaining two resulted in mild structural changes. This study's results provided multiple lines of computational pathogenicity evidence for eight ABCA4 variants of uncertain clinical significance. Overall, in silico analyses of ABCA4 can provide a valuable tool for understanding the molecular mechanisms of retinal degeneration and their pathogenic impact.

Automatic multi-leaf nonperiodic block-by-block pattern generation and computational analysis of historical masonry structures

In this paper, an automatic block-by-block pattern generator is proposed for multi-leaf nonperiodic masonries. The outcome is then directly employed in block-based computational analysis of full-scale historical masonry structures. Given the 3D volume of the structure (obtainable also from point clouds) and the 3D block definition of a sample, both in terms of voxels, the volume of the structure is automatically filled with blocks by keeping the blocks statistics of the sample, as well as accounting for through-thickness blocks and structural details, such as lintels and edges. A meaningful benchmark is used to assess the efficiency of the filling algorithm, as well as its capability to generate statistically-consistent patterns. The benchmark is then employed in full-scale computational analyses by using an available block-based model. Various multi-leaf patterns are considered and critically compared in structural analysis, highlighting the influence of through-thickness blocks and intralayer mechanical properties on the overall structural response.

Aerospace grade acoustic metamaterial design, modeling, and experimental validation

Vertical Take-Off and Landing Urban Aerial Mobility vehicle propulsion systems use rotors and blades to achieve lift, which results in heightened noise at the blade passing frequency. These frequencies must be attenuated to reduce cabin discomfort and comply with noise exposure limits. The design must absorb 350 Hz noise, be fire retardant to comply with aviation standards, and be maximally one inch thick. This paper outlines the design, computational simulation, and experimental validation of a novel aerospace-grade acoustic metamaterial. It contributes to the field of computational analysis of new metamaterial structures and experimental validation using prototype Helmholtz unit cells. Achieving maximum sound absorption with the aerospace requirements of minimal mass and fire safety led to the consideration of Nomex honeycomb Helmholtz resonator acoustic panels. Their sub-wavelength attenuation, tunability, lightweight and fire resistance make them an optimal fit for this application. A novel phenomenon was observed in experimental impedance tube testing where multiple Nomex honeycomb cells acted as one resonator cavity. This discovery allowed for samples of only one inch in thickness (cell depth) to achieve 83% sound absorption at 348 Hz. Experimental values match well with the calculated analytical solution using the Helmholtz equation and simulated sound absorption in COMSOL MultiPhysics. The acoustic metamaterial achieves tunable noise attenuation with minimal thickness, weight, and fire suppression using a novel design.

Computational analysis of geometric structures and edge‐termination effects of boron‐nitride and edge‐termination boron‐nitride nanoribbons

AbstractIn this work, we examined geometry, electronic structure, and edged termination effect of boron‐nitride nanoribbons (BNNRs) by employing localized Gaussian‐type orbital, periodic‐boundary condition, density functional theory (LGTO‐PBC‐DFT) calculations. Armchair (ABNNR) and zigzag (ZBNNR)‐type BNNRs are obtained and then bond lengths variation in two types of BNNRs are analyzed. We find that the B‐N bond length variation of ZBNNR is less diverse than that of ABNNR, and decreases with an increase in the ribbon width, monotonically. For those in ABNNR, it appears as an oscillatory convergence as a function of the ribbon width. The energy gap of edged termination ABNNR and ZBNNRs are also calculated using OH and SH as electron donating groups and CN‐, and Cl‐ as electron‐withdrawing groups. The introduction of SH‐ and Cl‐terminator significantly reduce the energy gap to the semiconducting region for ZBNNR, but for ABNNR. These calculated results may be exploited for nano‐electronic applications. To examine the surface behavior of the BNNRs, we also calculated their Raman shifts with the edge termination effects.

Experimental and computational analysis of polymeric lattice structure for efficient building materials

• A novel building envelop based on spatial distribution of material to form the periodic lattice architecture. • For a given relative density of the lattice, the unit-cell size governs the mode of heat transfer. • The unit-cell orientation plays a significant role in defining the thermal performance of the lattice based structures. • Conductive mode of hear transfer dominates the thermal transmittance of the polymer lattices. A continuous increase in energy prices and the growing concern about global warming has created an urge to increase the energy efficiency of residential buildings. In this paper, the reduction of heat loss by incorporating porosity in a monolithic material was studied. To this aim, various sizes of the polymer-based lattice panels were developed using a triangular unit cell. A new technique based on moulding was used to develop commercial size (1 m 2 ) panels which were not possible with normal 3D printers. A novel, experimental results-based, scaling law was used to predict the thermal performances of these polymer lattice-based panels. Besides, the thermal performance of these lattice-based panels was also investigated using an in-house built calorimeter box and a commercial guard hot box chamber by exposing them to a temperature difference of around 30°C. It was observed that the scaling up of the unit cell size to manufacture commercial-size panels did not affect its U-value; even though the heat transfer through the lattice cell is heavily dependent on the unit cell size. It was also observed that the hydraulic diameter of the polymer-lattice structures of value less than 8mm leads only to a conductive mode of heat transfer. The effect of testing parameters such as sensor location and the temperature gradient across lattice on the U-value of the polymer lattice was also characterised and made recommendations for achieving the higher thermal resistance of the lattice panels to make them suitable for the energy-saving in building applications.

Computational analysis on flow induced stress and acoustic vibration in a proposed silencer design for a three-cylinder in-line four-stroke spark ignition engine

Computational analysis of flowing exhaust gases inside a non-perforated silencer chamber of a commercially available three-cylinder inline four-stroke spark-ignition engine and in a modified perforated design was conducted and their respective levels of performance were predicted. Study on the existing and proposed silencer designs was carried out by way of computational fluid dynamics (CFD) analysis, structural analysis and modal analysis. Modal analysis has been performed in order to compute up to six fundamental frequencies on the aforementioned structure for analysing the response spectra for obtaining the natural frequencies at different modes of excitation. A reduction of 23.8% and 23.6% in the maximum values of static pressure and total pressure, respectively, has been observed for the proposed perforated model against the existing non-perforated silencer. The maximum acoustic power level and the maximum surface acoustic power level were found to be 9.5% and 7.3% respectively, less for the proposed design.

Computational molecular structure analysis, electronic properties of sudan dye doped thioureabarium chloride crystals for nlo Applications

Pure thiourea barium chloride (TBC) crystals were grown by slow evaporation from aqueous solution and slow cooling (0.1oC/ day). The growth was carried out for 21 days by keeping the bath at a temperature of 39oC. Optimal molecular structures are explored by DFT / B3LYP method with 6-31G (d, p) based synthesis. Hyper conjugative interactions, charge delocalization and intra molecular hydrogen bonding have been analyzed using natural bond orbital (NBO) analysis. Moreover lower in the HOMO and LUMO energy gap explains the eventual charge transfer interactions taking place within the molecule, which influences the biological activity of the compound and also energy serves as a measure of the excitability of a compound, the smaller the energy gap, the more easily the compound will be excited. Electronic structures were discussed and the displacement of the electron density was determined. Second – order perturbation theory analysis of the intra molecular bonds of Methyl Orange doped TBC were derived.

Computational Structural Analysis for Torsional Stiffness Test of Intermediate Shaft Assembly

Computational Structural Analysis for Torsional Stiffness Test of Intermediate Shaft Assembly

A stochastic approach for upgrading Cultural Heritage framed concrete buildings by cable-ties to prevent progressive collapse under seismic sequences

Old industrial reinforced concrete (RC) structures included to built Cultural Heritage are subjected sometimes to obligatory removal of some structural element-members, e.g. columns. In such cases, a modification of the structural response and a redistribution of internal actions can result to a requirement for upgrading the remaining structure after the removal of the degraded elements in order to avoid a progressive collapse. The present study deals with such a case, which concerns the stochastic computational analysis of historic framed RC structures under the removal of some columns and the so-induced requirement of a strengthening by ties (tension only elements). The unilateral behaviour of these cable-ties, which can undertake only tension, is strictly considered. The response under seismic sequences of the remaining historic RC structure strengthened by ties is computed considering uncertain-but-bounded input parameters.

Synthesis, crystal structure, and chromotropism properties of Dihalo N-2-ethanolpicolylamine copper(II)

Two copper (II) mononuclear complexes with the general formula [Cu(HL)X2], which L = N-2-ethanolpicolylamine and X = Cl, Br, were synthesized and characterized by elemental analysis infrared, electronic absorption spectroscopy techniques, and conductivity method. The distorted square pyramidal geometry of [Cu(HL)Cl2] was confirmed by the density functional theory level (DFT) calculation and X-ray crystallography. The complexes are soluble in polar solvents and are chromotropic. It was found both complexes have a similar identity in aqueous solution due to dissociation of halides and hydration. Their chromotropism behavior, including solvato-, thermos- and halochromism, was investigated using visible absorption spectroscopy. The original green complex displayed a reversible color change to blue in alkaline and almost colorless in acidic solutions. The pH effect on the visible absorption spectrum of the complex was studied that functions as pH-induced “off–on-off” switches triggered by the deprotonation of ligand in an alkaline aqueous solution and protonation along with loss of the ligand HL in an acidic medium. The complex also exhibited thermochromism and solvatochromism due to solvation and structural change. Further computational analysis of the electronic structure of the complex in different solvents was executed to gain a deeper insight into the properties associated with molecular orbitals. Its electronic spectrum was analyzed, and bands were assigned through the time-dependent density functional theory level (TDDFT) calculation, together with DFT-based molecular modeling

A bias of Asparagine to Lysine mutations in SARS-CoV-2 outside the receptor binding domain affects protein flexibility.

COVID-19 pandemic has been threatening public health and economic development worldwide for over two years. Compared with the original SARS-CoV-2 strain reported in 2019, the Omicron variant (B.1.1.529.1) is more transmissible. This variant has 34 mutations in its Spike protein, 15 of which are present in the Receptor Binding Domain (RBD), facilitating viral internalization via binding to the angiotensin-converting enzyme 2 (ACE2) receptor on endothelial cells as well as promoting increased immune evasion capacity. Herein we compared SARS-CoV-2 proteins (including ORF3a, ORF7, ORF8, Nucleoprotein (N), membrane protein (M) and Spike (S) proteins) from multiple ancestral strains. We included the currently designated original Variant of Concern (VOC) Omicron, its subsequent emerged variants BA.1, BA2, BA3, BA.4, BA.5, the two currently emerging variants BQ.1 and BBX.1, and compared these with the previously circulating VOCs Alpha, Beta, Gamma, and Delta, to better understand the nature and potential impact of Omicron specific mutations. Only in Omicron and its subvariants, a bias toward an Asparagine to Lysine (N to K) mutation was evident within the Spike protein, including regions outside the RBD domain, while none of the regions outside the Spike protein domain were characterized by this mutational bias. Computational structural analysis revealed that three of these specific mutations located in the central core region, contribute to a preference for the alteration of conformations of the Spike protein. Several mutations in the RBD which have circulated across most Omicron subvariants were also analysed, and these showed more potential for immune escape. This study emphasizes the importance of understanding how specific N to K mutations outside of the RBD region affect SARS-CoV-2 conformational changes and the need for neutralizing antibodies for Omicron to target a subset of conformationally dependent B cell epitopes.

MPEX High Heat Flux Plasma Dump Design, Manufacture, and Articles Test

The Material Plasma Exposure eXperiment (MPEX) device is a steady-state linear plasma device currently in the final design phase at the Oak Ridge National Laboratory. This device will reach ion fluences up to <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$10^{31}\,\,\text{m}^{-2}$ </tex-math></inline-formula> and will be used to expose neutron-irradiated materials to divertor-relevant plasmas and to study the effects of plasma-material interactions. These studies will elucidate the complex effects of plasmas with divertor candidate materials capable of withstanding high heat flux and high fluences for next-generation fusion devices. Bidirectional plasma will be generated using a high-power (200 kW) helicon source. Plasma will be confined by superconducting magnets. The last plasma-facing component on the upstream side of the MPEX device is the dump, which has been designed to intercept plasma and energetic particles. The dump will have a total heat load of 9.2 kW. A copper alloy (Glidcop AL-15) was selected for use in the water-cooled flange design because of its high thermal conductivity, its retaining strength at elevated temperatures, and its ability to be used in the high-temperature braze joints used in this application. Titanium-zirconium-molybdenum (TZM) tiles are brazed to the Glidcop AL-15 flange using high-temperature braze alloy. External water-cooling channels are used on the dump flange to prevent water leakage inside the vacuum space. This article discusses the details of the high heat flux dump design, including the computational fluid dynamics (CFD) and structural analyses performed to validate the design to meet the operational requirements of the MPEX device.

Diagnostics of the RC Roofing Structure of the 100-Year-Old Municipal Theatre Facility.

Reinforced concrete has been a widely used material for the construction of buildings for many decades. However, with the passage of time, the material characteristics and connection of structural elements gradually degrade. Development in measurement technology makes it possible to efficiently obtain data on the current state of the structure and material characteristics using non-destructive methods, with limited or no destructive testing. The paper presents the analysis of the condition of the reinforced concrete roof of a 100-year-old theatre building in terms of its further use after planned modernisation. The tests carried out in situ as well as the computational analysis of structure are described. Based on the test results, the current load-bearing capacity was assessed and the limit state conditions were checked. Limitations on the accuracy of the non-destructive test results in relation to the destructive test results were formulated. Options for the strengthening reinforced concrete beams with regard to structural and technological considerations were analysed.

Investigating Oxidative Addition Mechanisms of Allylic Electrophiles with Low-Valent Ni/Co Catalysts Using Electroanalytical and Data Science Techniques.

The catalysis by a π-allyl-Co/Ni complex has drawn significant attention recently due to its distinct reactivity in reductive Co/Ni-catalyzed allylation reactions. Despite significant success in reaction development, the critical oxidative addition mechanism to form the π-allyl-Co/Ni complex remains unclear. Herein, we present a study to investigate this process with four catalysis-relevant complexes: Co(MeBPy)Br2, Co(MePhen)Br2, Ni(MeBPy)Br2, and Ni(MePhen)Br2. Enabled by an electroanalytical platform, Co(I)/Ni(I) species were found responsible for the oxidative addition of allyl acetate. Kinetic features of different substrates were characterized through linear free-energy relationship (Hammett-type) studies, statistical modeling, and a DFT computational study. In this process, a coordination-ionization-type transition state was proposed, sharing a similar feature with Pd(0)-mediated oxidative addition in Tsuji-Trost reactions. Computational and ligand structural analysis studies support this mechanism, which should provide key information for next-generation catalyst development.

Computational and Crystallographic Analysis of Binding Structures of Inhibitory Compounds for HIV-1 RNase H Activity.

Chemotherapy of human immunodeficiency virus type-1 (HIV-1) has significantly developed over the last three decades. The emergence of drug-resistant variants is, however, still a severe problem. The RNase H activity of HIV-1 reverse transcriptase is an attractive target for a new class of antiviral drugs because there is no approved inhibitor. The nitro-furan-carbonyl and nitro-thiophene-carbonyl groups are potent scaffolds for the HIV-1 RNase H inhibitor. In this work, the binding structures of six inhibitory compounds were obtained by X-ray crystal analysis in a complex with a recombinant protein of HIV-1 RNase H domain. Every inhibitory compound was found to be bound to the catalytic site with the furan- or thiophene-ring coordinated to two divalent metal ions at the binding pocket. All the atoms in nitro, furan, carbonyl, and two metals were aligned in the nitro-furan derivatives. The straight line connecting nitro and carboxyl groups was parallel to the plane made by two metal ions and a furan O atom. The binding modes of the nitro-thiophene derivatives were slightly different from those of the nitro-furan ones. The nitro and carbonyl groups deviated from the plane made by two metals and a thiophene S atom. Molecular dynamics simulations suggested that the furan O or thiophene S atom and carbonyl O atom were firmly coordinated to the metal ions. The simulations made the planar nitro-furan moiety well aligned to the line connecting the two metal ions. In contrast, the nitro-thiophene derivatives were displaced from the initial positions after the simulations. The computational findings will be a sound basis for developing potent inhibitors for HIV-1 RNase H activity.

Resolution of Identity in Gas-Phase Dissociations of Mono- and Diprotonated DNA Trinucleotide Codons by 15N-Labeling and Computational Structure Analysis.

Dissociations of DNA trinucleotide codons as gas-phase singly and doubly protonated ions were studied by tandem mass spectrometry using 15N-labeling to resolve identity in the nucleobase loss and backbone cleavages. The monocations showed different distributions of nucleobase loss from the 5'-, middle, and 3'-positions depending on the nucleobase, favoring cytosine over guanine, adenine, and thymine in an ensemble-averaged 62:27:11:<1 ratio. The distribution for the loss of the 5'-, middle, and 3'-nucleobase was 49:18:33, favoring the 5'-nucleobase, but also depending on its nature. The formation of sequence w2+ ions was unambiguously established for all codon mono- and dications. Structures of low-Gibbs-energy protomers and conformers of dAAA+, dGGG+, dCCC+, dTTT+, dACA+, and dATC+ were established by Born-Oppenheimer molecular dynamics and density functional theory calculations. Monocations containing guanine favored classical structures protonated at guanine N7. Structures containing adenine and cytosine produced classical nucleobase-protonated isomers as well as zwitterions in which two protonated bases were combined with a phosphate anion. Protonation at thymine was disfavored. Low threshold energies for nucleobase loss allowed extensive proton migration to occur prior to dissociation. Loss of the nucleobase from monocations was assisted by neighboring group participation in nucleophilic addition or proton abstraction, as well as allosteric proton migrations remote from the reaction center. The optimized structures of diprotonated isomers for dAAA2+ and dACA2+ revealed combinations of classical and zwitterionic structures. The threshold and transition-state energies for nucleobase-ion loss from dications were low, resulting in facile dissociations involving cytosine, guanine, and adenine.

Computational Analysis of Structure - Activity Relationships in Highly Active Homogeneous Ruthenium-based Water Oxidation Catalysts.

Linear free energy scaling relationships (LFESRs) and regression analysis may predict the catalytic performance of heterogeneous and recently, homogenous water oxidation catalysts (WOCs). This study analyses twelve homogeneous Ru-based catalysts - some, the most active catalysts studied: the Ru(tpy-R)(QC) and Ru(tpy-R)(4-pic)2 catalysts, where tpy is 2,2:6,2-terpyridine, QC is 8-quinolinecarboxylate and 4-pic is 4-picoline. Typical relationships studied among heterogenous and solid-state catalysts cannot be broadly applied to homogeneous catalysts. This subset of structurally similar catalysts with impressive catalytic activity deserves closer computational and statistical analysis of energetics correlating with measured catalytic activity. We report general methods of LFESR analysis yield insufficiently robust relationships between descriptor variables. However, volcano plot-based analysis grounded in Sabatier's principle reveals ranges of ideal relative energies of the RuIV=O and RuIV-OH intermediates and optimal changes in free energies of water nucleophilic attack on RuV=O. A narrow range of RuIV-OH to RuV=O redox potentials corresponding with the highest catalytic activities suggests facile access to the catalytically competent high-valent RuV=O state, often inaccessible from RuIV=O. Our work introduces experimental oxygen evolution rates into approaches of LFESR and Sabatier principle-based analysis, identifying a narrow yet fertile energetic landscape to bountiful oxygen-evolution activity, leading future rational design.

Synthesis, characterization, and thermal and computational investigations of the l-histidine bis(fluoride) crystal

Nonlinear optical materials have been investigated recently due to their potential technological applications in information storage and communications. In this context, semi-organic crystals can effectively combine the desired nonlinear optical properties of amino acids with the promising mechanical and thermal properties of inorganic materials. In this work, we have synthesized and characterized a semi-organic crystal of the amino acid l-histidine and hydrofluoric acid and investigated the chemical interactions between the organic and inorganic moieties. The crystal of l-histidine bis(fluoride) has been produced by slow solvent evaporation and characterized by X-ray diffraction (XRD) crystallography and thermogravimetric and differential thermal analyses. The XRD conducted using the Rietveld method shows that the unit cell is orthorhombic with the P21212 space group and contains four l-histidine bis(fluoride) units. Both differential thermal analysis and temperature-dependent XRD show that the crystals are thermally stable up to 191°C and do not undergo phase transition. The computational Hirshfeld surface analysis of the crystal structure reveals the main intermolecular interactions. Density functional theory has been employed to calculate the ionic interaction energy and electrostatic potential maps and confirm the spontaneity of ionic association at 191°C. The combined experimental and computational results show that the thermal stability of the semi-organic l-histidine bis(fluoride) crystal makes it suitable for nonlinear optical applications in optical sensing and communication systems.Graphical abstract