Stacking Contacts Research Articles

Photophysics and Excited State Dynamics of Cyclometalated [M(Phbpy)(CN)] (M = Ni, Pd, Pt) Complexes: A Theoretical and Experimental Study.

Cyclometalated complexes [M(Phbpy)(CN)] (HPhbpy = 6-phenyl-2,2'-bipyridine) of the group 10 metals (Ni, Pd, and Pt) bearing a carbanionic -C∧N∧N pincer ligand were synthesized and studied in a combined experimental and computational DFT approach. All three complexes were crystallographically characterized showing closely packed dimers with head-to-tail stacking and short metal-metal contacts in the solid state. The computational models for geometries, excited states, and electronic transitions addressed both monomeric (Ni-mono, Pd-mono, and Pt-mono) and dimeric (Ni-dim, Pd-dim, and Pt-dim) entities. Photophysical properties and excited state dynamics of all title complexes were investigated in solution and in the solid at 298 and 77 K. [Ni(Phbpy)(CN)] and [Pd(Phbpy)(CN)] are virtually nonemissive in solution at 298 K, whereas [Pt(Phbpy)(CN)] shows phosphorescence in CH2Cl2 (DCM) solution (λem = 562 nm) stemming from a mixed 3MLCT/ILCT (metal-to-ligand charge transfer/intraligand charge transfer) state. At 77 K in a glassy frozen DCM:MeOH matrix, [Pd(Phbpy)(CN)] shows a remarkable emission (λem = 571 nm) with a photoluminescence quantum yield reaching almost unity, whereas [Ni(Phbpy)(CN)] is again nonemissive. Calculations on the monomeric models M-mono show that low-lying metal-centered states (MC, i.e., d-d* configuration) with dissociative character quench the photoluminescence. In the solid state, the complexes [M(Phbpy)(CN)] show defined photoluminescence bands (λem = 561 nm for Pd and 701 nm for Pt). Calculations on the dimeric models M-dim shows that the axial M···M interactions alter the photophysical properties of Pd-dim and Pt-dim toward MMLCT (metal-metal-to-ligand charge transfer) excited states with Pd-dim showing temperature-dependent emission lifetimes, suggesting thermally activated delayed fluorescence, whereas Pt-dim displayed phosphorescence with excimeric character. The metal-metal interactions were analyzed in detail with the quantum theory of atoms in molecules approach.

Protein-Ligand Interactions in the STING Binding Site Probed by Rationally Designed Single-Point Mutations: Experiment and Theory.

STING protein (stimulator of interferon genes) plays an important role in the innate immune system. A number of potent compounds regulating its activity have been reported, mostly derivatives of cyclic dinucleotides (CDNs), natural STING agonists. Here, we aim to provide complementary information to large-scale "ligand-profiling" studies by probing the importance of STING-CDN protein-ligand interactions on the protein side. We examined in detail six typical CDNs each in complex with 13 rationally devised mutations in STING: S162A, S162T, Y167F, G230A, R232K, R232H, A233L, A233I, R238K, T263A, T263S, R293Q, and G230A/R293Q. The mutations switch on and off various types of protein-ligand interactions: π-π stacking, hydrogen bonding, ionic pairing, and nonpolar contacts. We correlated experimental data obtained by differential scanning fluorimetry, X-ray crystallography, and isothermal titration calorimetry with theoretical calculations. This enabled us to provide a mechanistic interpretation of the differences in the binding of representative CDNs to STING. We observed that the G230A mutation increased the thermal stability of the protein-ligand complex, indicating an increased level of ligand binding, whereas R238K and Y167F led to a complete loss of stabilization (ligand binding). The effects of the other mutations depended on the type of ligand (CDN) and varied, to some extent. A very good correlation (R2 = 0.6) between the experimental binding affinities and interaction energies computed by quantum chemical methods enabled us to explain the effect of the studied mutations in detail and evaluate specific interactions quantitatively. Our work may inspire development of high-affinity ligands against the common STING haplotypes by targeting the key (sometimes non-intuitive) protein-ligand interactions.

Synthesis, X-ray Structure, Hirshfeld Analysis of Biologically Active Mn(II) Pincer Complexes Based on s-Triazine Ligands

Herein, the synthesis and antimicrobial activities of [Mn(MorphBPT)(H2O)2NO3]NO3; (1) and [Mn(PipBPT)(H2O)2NO3]NO3; (2) complexes of the pincer-type tridentate ligands MorphBPT; 4-(4,6-di(1H-pyrazol-1-yl)-1,3,5-triazin-2-yl)morpholine and PipBPT; 2-(piperidin-1-yl)-4,6-di(1H-pyrazol-1-yl)-1,3,5-triazine are presented. Both complexes have slightly distorted octahedral coordination geometry. Their molecular packing depends on O–H···O, C–H···O hydrogen bonds and anion–π stacking contacts. Hirshfeld analysis was used to quantify the different contacts. Both complexes exhibited better anti-fungal activity than the standard Fluconazole and comparable antibacterial activity to Gentamycin against Staphylococcus aureus and Escherichia coli microbes. Moreover, complexes 1 and 2 are biologically more active than the free ligands against these microbes.

σ-Hole interactions in small-molecule compounds containing divalent sulfur groups R1-S-R2.

Hydrogen bonds, aromatic stacking contacts and σ-hole interactions are all noncovalent interactions commonly observed in biological systems. Structural data derived from the Protein Data Bank showed that methionine residues can interact with oxygen atoms through directional S...O contacts in the protein core. In the present work, the Cambridge Structural Database (CSD) was used in conjunction with ab initio calculations to explore the σ-hole interaction properties of small-molecule compounds containing divalent sulfur. CSD surveys showed that 7095 structures contained R1-S-R2 groups that interact with electronegative atoms like N, O, S and Cl. Frequencies of occurrence and geometries of the interaction were dependent on the nature of R1 and R2, and the hybridization of carbon atoms in C,C-S, and C,S-S fragments. The most common interactions in terms of frequency of occurrence were C,C-S...O, C,C-S...N and C,C-S...S with predominance of Csp2. The strength of the chalcogen interaction increased when enhancing the electron-withdrawing character of the substituents. The most positive electrostatic potentials (VS,max; illustrating positive σ-holes) calculated on R1-S-R2 groups were located on the S atom, in the S-R1 and S-R2 extensions, and increased with electron-withdrawing R1 and R2 substituents like the interaction strength did. As with geometric data derived from the CSD, interaction geometries calculated for some model systems and representative CSD compounds suggested that the interactions were directed in the extensions of S-R1 and S-R2 bonds. The values of complexation energies supported attractive interactions between σ-hole bond donors and acceptors, enhanced by dispersion. The interactions of R1-S-R2 with large VS,max and nucleophiles with large negative VS,min coherently provided more negative energies. According to NBO analysis, chalcogen interactions consisted of charge transfer from a nucleophile lone pair to an S-R1 or S-R2 antibonding orbital. The directional σ-hole interactions at R1-S-R2 can be useful in crystal engineering and the area of supramolecular biochemistry.

Microstructural Characterization of Multilayer Metal Stack on InGaAs/InP Contact

Al/InGaAs, Al/Ti/InGaAs, and Al/Ni/InGaAs contacts were prepared by conducting rapid thermal annealing at different temperatures, and the interfacial reaction was characterized using x-ray diffraction, atomic force microscopy, and transmission electron microscopy. The specific contact resistivity of the metal film contacts on n-InGaAs was determined using a circular transmission line measurement. The Al/Ni/InGaAs, Al/Ti/InGaAs, and Al/InGaAs stack contacts remained stable even after the samples were subjected to annealing at 400°C. When the annealing temperature increased to 600°C, Al began melting and clustering due to the formation of Al(Ga) to form Al/InGaAs. An AlNi phase was formed at the interfaces of an Al/Ni/InGaAs contact when it was annealed above 400°C, thus causing the specific resistance and roughness to increase dramatically. Each element of the Al/Ti/InGaAs contact began diffusing when it was annealed beyond 400°C, and an Al3Ti phase was formed above 500°C. The formation of Al3Ti led to the increase in the specific resistance and roughness. Moreover, the as-deposited Al/Ni/InGaAs, Al/Ti/InGaAs and Al/InGaAs samples had specific resistances of 1.11 × 10−5 Ω cm2, 5.11 × 10−5 Ω cm2, and 1.14 × 10−4 Ω cm2, respectively. These results reveal that to develop the Al/Ti/InGaAs and Al/Ni/InGaAs stacks on InGaAs with a low parasitic resistance, the processing temperature should be lower than 400°C.

Syntheses, structure, Hirshfeld analysis and antimicrobial activity of four new Co(II) complexes with s-triazine-based pincer ligand

The [Co(BPMT)(H2O)2Cl]Cl; (1), [Co(BPMT)(H2O)3](ClO4)2·H2O; (2), [Co(BPMT)(NO3)2]; (3) and [Co(BPMT)(H2O)3](NO3)2·H2O; (4) pincer complexes of 2,4-bis(3,5-dimethyl-1H-pyrazol-1-yl)-6-methoxy-1,3,5-triazine, (BPMT) ligand were synthesized by self-assembly technique in methanol as solvent. In all complexes, the BPMT acting as a tridentate N-donor pincer ligand. The Co(II) is hexa-coordinated in complexes 1, 2 and 4 with distorted octahedral coordination geometry while 3 has a rare hepta-coordinated Co(II) comprised a CoN3O4 coordination sphere with two bidentate nitrate ions as ligand. In 1, the most important contacts are the Cl…H (16.5%) and O…H (9.8%) interactions. For complexes 2–4, the O…H and C…O (anion-π stacking) contacts are the most important. The percentages of O…H contacts are 40.2, 39.2–37.2 and 36.4% in complexes 2–4, respectively while the percentages of C…O (anion-π stacking) contacts are 2.8, 3.2–3.7 and 2.5%, respectively. The natural charge populations of the cobalt central metal ion (Co(II)) are decreased to 0.891, 0.948, 0.950–0.953 and 0.951 e due to the interactions with the ligand groups coordinating it. The antimicrobial activity of complexes 1–3 were evaluated and compared with some commercial antibiotics. Complex 1 has better antimicrobial activity against all microbes compared to complexes 2 and 3. Also, 1 and 2 performed better than Amoxicillin, Tetracycline and Ampicillin antibiotics against E. coli and C. albicans.

Occurrence and stability of lone pair-π and OH-π interactions between water and nucleobases in functional RNAs.

We identified over 1000 instances of water-nucleobase stacking contacts in a variety of RNA molecules from a non-redundant set of crystal structures with resolution ≤3.0 Å. Such contacts may be of either the lone pair-π (lp–π) or the OH–π type, in nature. The distribution of the distances of the water oxygen from the nucleobase plane peaks at 3.5 Å for A, G and C, and approximately at 3.1–3.2 Å for U. Quantum mechanics (QM) calculations confirm, as expected, that the optimal energy is reached at a shorter distance for the lp–π interaction as compared to the OH–π one (3.0 versus 3.5 Å). The preference of each nucleobase for either type of interaction closely correlates with its electrostatic potential map. Furthermore, QM calculations show that for all the nucleobases a favorable interaction, of either the lp–π or the OH–π type, can be established at virtually any position of the water molecule above the nucleobase skeleton, which is consistent with the uniform projection of the OW atoms over the nucleobases ring we observed in the experimental occurrences. Finally, molecular dynamics simulations of a model system for the characterization of water-nucleobase stacking contacts confirm the stability of these interactions also under dynamic conditions.

RNA-Puzzles Round IV: 3D structure predictions of four ribozymes and two aptamers.

RNA-Puzzles is a collective endeavor dedicated to the advancement and improvement of RNA 3D structure prediction. With agreement from crystallographers, the RNA structures are predicted by various groups before the publication of the crystal structures. We now report the prediction of 3D structures for six RNA sequences: four nucleolytic ribozymes and two riboswitches. Systematic protocols for comparing models and crystal structures are described and analyzed. In these six puzzles, we discuss (i) the comparison between the automated web servers and human experts; (ii) the prediction of coaxial stacking; (iii) the prediction of structural details and ligand binding; (iv) the development of novel prediction methods; and (v) the potential improvements to be made. We show that correct prediction of coaxial stacking and tertiary contacts is essential for the prediction of RNA architecture, while ligand binding modes can only be predicted with low resolution and simultaneous prediction of RNA structure with accurate ligand binding still remains out of reach. All the predicted models are available for the future development of force field parameters and the improvement of comparison and assessment tools.

Generalized stacked contact process with variable host fitness

AbstractThe stacked contact process is a three-state spin system that describes the co-evolution of a population of hosts together with their symbionts. In a nutshell, the hosts evolve according to a contact process while the symbionts evolve according to a contact process on the dynamic subset of the lattice occupied by the host population, indicating that the symbiont can only live within a host. This paper is concerned with a generalization of this system in which the symbionts may affect the fitness of the hosts by either decreasing (pathogen) or increasing (mutualist) their birth rate. Standard coupling arguments are first used to compare the process with other interacting particle systems and deduce the long-term behavior of the host–symbiont system in several parameter regions. The spatial model is also compared with its mean-field approximation as studied in detail by Foxall (2019). Our main result focuses on the case where unassociated hosts have a supercritical birth rate whereas hosts associated to a pathogen have a subcritical birth rate. In this case, the mean-field model predicts coexistence of the hosts and their pathogens provided the infection rate is large enough. For the spatial model, however, only the hosts survive on the one-dimensional integer lattice.

Antiproliferative evaluation and supramolecular association involving electrostatically enhanced π-π interaction in isostructural coordination solids of Mn(II), Co(II) and Zn(II) chlorobenzoates: Experimental and theoretical studies

Three new isostructural coordination solids viz. [Co(3-CNpy)2(2-ClBz)2(H2O)2] (1), [Mn(3-CNpy)2(2-ClBz)2(H2O)2] (2) and [Zn(3-CNpy)2(2-ClBz)2(H2O)2] (3) (3-CNpy = 3-cyanopyridine, 2-ClBz = 2-chlorobenzoate) have been synthesized from purely aqueous media and characterized by X-ray crystal structure analysis, FT-IR, electronic spectra and TGA. Several non-covalent hydrogen bonding interactions of the types OH⋯O, CH⋯O, CH⋯N, CH⋯Cl and π-π stacking contacts build up the supramolecular networks in the crystal structures. Electrostatically enhanced π-π interactions are observed in 1–3 between the phenyl rings of 2-ClBz and pyridine ring of 3-CNpy of the monomeric units of the complexes. We have used the molecular DFT calculations to evaluate energetically the strength of these contacts and also to analyze the effect of the metal on the interaction energies. The energetic features of the H-bonding and π-stacking interactions for 1–3 reveal that the H-bonded assembly is more favorable than the π-stacked contacts. The electrostatically enhanced energy of the π-stacking interactions is stronger than that usually observed for π-stacking interactions involving arenes. The cytostatic potential of all complexes have been studied in Dalton’s lymphoma (DL) cell line by MTT assay, apoptosis assay and further corroborated with molecular docking simulation. The complexes exhibit cytotoxicity (∼25–30%) through apoptotic cell death with negligible cytotoxicity (∼5–10%) in normal PBMC cells. In silico-docking techniques have been performed with apoptosis regulator protein BCL-2 for the identification of critical amino acids and their possible binding affinity with the synthesized complexes. The pharmacophore features based on structure activity relationship (SAR) of the complexes have been identified and the study reveal that the features viz., hydrophobic, aromatic, positive ionizable, negative ionizable, H-bond donor and acceptor and halogen bond donor properties play important role for the biological activities of the complexes.

Assessing the operating temperature of multi-junction solar cells with novel rear side layer stack and local electrical contacts

Sub-bandgap sunlight provides a source of heat generation in solar cells that is detrimental to performance, especially in space applications where heat dissipation is limited. In this work we assess the impact that an advanced rear-side contact scheme for multi-junction solar cells has on the cell temperature. Our results show that this scheme reduces the optical power absorption below the bandgap of germanium by 81% compared to a standard, full metallization design. Measurements of the electrical and thermal power fluxes performed in vacuum demonstrate that this lower near-infrared light absorption results in 8% less heat dissipated in the cell with the novel rear-side contact scheme when operating at 25 °C. Modelling of the operating temperature for both cells when fully encapsulated with glass indicates that this effect will also result in a reduction of the operating temperature of 9 °C for the novel design.

Picosecond laser welding of glasses with a large gap by a rapid oscillating scan.

A welding method that utilizes a picosecond laser with a small-scale rapid oscillating scan is presented in this Letter to achieve the welding of glasses with natural stacking contact (gap≈10 μm). The rapid oscillating scan of the laser not only creates enough molten material to fill the gap, but also releases the internal thermal pressure during the welding process. The contraction created by condensation of the welding area can reduce the gap to less than 3μm, which provides necessary conditions for realizing continuous welding. By using this method, a maximum joint strength up to 64MPa can be achieved without any defects. The detail mechanism of laser welding with a rapid oscillating scan was revealed in this Letter. This research lays a good foundation for the laser welding of large-gap glass in practical engineering applications.

Synthesis, Crystal Structure and Non-covalent Interactions Analysis of Novel N-substituted Thiosemicarbazone

(E)-1-(4-Fluorobenzylidene)-4-(4-ethylphenyl)thiosemicarbazone was synthesized via the reaction of 4-(4-ethylphenyl)thiosemicarbazide and 4-fluorobenzaldehyde. The title compound was characterized by FTIR, 1H and 13C NMR, mass spectrometry and elemental analysis techniques. Structural property of the title compound was displayed by the X-ray single crystal diffraction. The title compound crystallized in triclinic space group $P\overline 1$ with a=0.6494(4) nm, b=0.7971(5) nm, c=1.5492(10) nm, α=83.690(11)°, β=84.185(10)°, γ=84.348(11)°, molecular formula C16H16FN3S, Mr=301.39, V=0.7868(9) nm3, Z=2, Dc=1.272 g/cm3, F(000)=316, μ=0.213 mm−1, S=1.02, R=0.0513, and ωR[I>2σ(I)]=0.1662. The intermolecular interactions in the crystal structure were explained using the Hirshfeld surface and their associated two-dimensional fingerprint plots. The title compound showed C—H⋯S(1−x, −y, −z) and N—H⋯S(1−x, −y, −z) intermolecular interactions, and formed the supramolecular self-assemblies through $$\overline G $$ and $${\rm{R}}_2^2(8)$$ ring motifs. Shape index and curvedness were performed to further understand some unique weak interactions, for instance, the weak π…π stacking contacts in molecular structure with different characteristic regions. Besides, the reduced density gradient(RDG) function provided a real-space function for discussing non-covalent interactions within molecule, such as hydrogen bonds, weak vdW interactions and attractive or repulsive effects.

Statistical analysis and heuristic identification of unexpected interactions from the neurokinase‐inhibitor interactome in trigeminal neuralgia pharmacological intervention

AbstractThe cell signaling pathways of human trigeminal neuralgia (TN) are orchestrated by a variety of protein kinase‐elicited phosphorylation events. However, a majority of TN‐related neurokinases have not yet been revealed and still remain largely unexplored. Here, a systematic kinase‐inhibitor interactome for 601 small‐molecule inhibitors across 51 human neurokinases is created via a high‐throughput molecular docking procedure; the inhibitors are reversible, ATP competitive, and commercially available, while the kinases are enriched by gene ontology (GO) to be semantically relevant with TN and have cocrystallized structures with their cognate ligands. Heuristic clustering and statistical analysis identify 35 hit inhibitors from the interactome profile, which are potential to target TN‐related kinases. The intermolecular interactions of four promising inhibitors with the array of 51 TN‐related kinases are investigated in detail at molecular level using dynamics simulation and energetics analysis. Consequently, a total of nine protein kinases are inferred as high‐affinity cotargets of these potent inhibitors, in which fours have already been established as sophisticated targets for TN therapy, while others are still unclear about their therapeutic implications underlying the disease. Some candidates are selected as representatives to perform kinase assay. It is found that some putative kinase targets can be inhibited effectively by noncognate inhibitors; the activity values are comparable with or even better than known cognate inhibitors. Structural examination of a potent kinase‐inhibitor complex identifies a number of noncovalent interactions such as hydrogen bonds, cation‐π stacking, and hydrophobic contacts at the tightly packed complex interface, conferring both stability and specificity to the complex recognition and interaction.

Electrical characterization of HVPE GaN containing different concentrations of carbon dopants

A comprehensive study of the electrical characteristics in Schottky diodes made of GaN:C grown by hydride vapour phase epitaxy (HVPE) technology has been reported. The Schottky junctions were made of an Ni/Au (25/200 nm) metal stack and ohmic contacts were fabricated by Ti/Al/Ni/Au (30/90/20/100 nm) e-beam deposition of the metal thin-films followed by rapid thermal annealing. A good quality of the fabricated Schottky diodes has been proved by considering the transient shape using a pulsed technique of barrier evaluation under linearly increasing voltage (BELIV). The concentrations of equilibrium carriers of 1 × 1011 cm−3 and of 2 × 1010 cm−3 have been evaluated for relatively low and high carbon density doped samples, respectively, using photo-capacitance characteristics dependent on excitation intensity. The effective mobility of carriers of μeff = 610 cm2/Vs has been estimated by considering the serial resistance variations dependent on excitation density, through analysis of delay times that appeared in the formation of peaks within BELIV transients. Optical deep level transient spectroscopy has shown that thermal emission from the rather shallow centres prevails. The centres, ascribed to vacancies as well as to carbon on Ga sites, have been identified. It has been demonstrated that Schottky junctions made of heavy carbon doped (NC ≥ 1018 cm−3) HVPE GaN material are able to withstand voltages of ≥300 V.

Structure-Based Stepwise Screening of PPARγ Antagonists as Potential Competitors with NCOA1 Coactivator Peptide for PPARγ CIS Site

The small-molecule modulators (agonists and antagonists) of peroxisome proliferator-activated receptor-γ (PPARγ) have been widely used to treat metabolic, cardiovascular and inflammatory diseases such as Type-2 diabetes and heart failure. Existing PPARγ modulators are all developed to target the ligand-binding site (LBS) in PPARγ ligand-binding domain (LBD) interior, where is spatially separated from the coactivator-interacting site (CIS) on PPARγ LBD surface and can thus only indirectly mediate the binding of NCOA1 coactivator peptide to CIS site. Here, we propose a new therapeutic strategy termed as Type-III PPARγ antagonists, which competitively disrupt the NCOA1 peptide binding by directly targeting PPARγ CIS site. Such antagonists are also known as inverse agonists that can partially or fully repress the basal transcriptional activity of PPARγ. A structure-based stepwise screening is performed against a purchasable biogenic compound library to identify CIS-specific binding competitors. The screening integrates empirical manual exclusion, druglikeness/pharmacokinetic evaluation, chemical similarity analysis and high-throughput molecular docking to rank the relative binding capability for compound candidate lists. The competitive potency of eight promising hits against a truncated version (core binding sequence) of full-length NCOA1 peptide (685ERHKILHRLLQEGSPS700) is tested using fluorescence competition assays. Consequently, two out of the eight tested compounds are determined as potential competitors with NCOA1 peptide for PPARγ CIS site, with CC50 values of 13 ± 1.8 and 54 ± 6.7 μM, respectively. Structural analysis reveals that the two competitor ligands are anchored at the central hole of CIS site through their substituted phenyl moieties, while forming a variety of hydrogen bonds, cation-π stacking and hydrophobic contacts with the regions surrounding the hole, conferring both stability and specificity to the CIS–competitor recognition and interaction.

A dibenzofuran derivative: 2-(pentyloxy)dibenzo[b,d]furan.

The title compound, C17H18O2, crystallizes in two-dimensional sheets, in which the 2-(pentyloxy)dibenzo[b,d]furan molecules are arranged in a head-to-head and tail-to-tail fashion that enables hydrophobic interactions between fully extended 2-pentoxy chains and π-π stacking between dibenzofuran rings in adjacent rings. Nearest intermolecular π-π stacking contacts are 3.3731 (12) Å. The molecule is nearly planar with an r.m.s. deviation of 0.0803 Å from the mean plane defined by the nineteen non-hydrogen atoms.

Integration of virtual screening and susceptibility test to discover active-site subpocket-specific biogenic inhibitors of Helicobacter pylori shikimate dehydrogenase.

Shikimate dehydrogenase (HpSDH) (EC 1.1.1.25) is a key enzyme in the shikimate pathway of Helicobacter pylori (H. pylori), which catalyzes the NADPH-dependent reversible reduction of 3-dehydroshikimate to shikimate. Targeting HpSDH has been recognized as an attractive therapeutic strategy against H. pylori infection. Here, the catalytic active site in the crystal structure of HpSDH in complex with its substrate NADPH and product shikimate was examined in detail; the site can be divided into three spatially separated subpockets that separately correspond to the binding regions of shikimate, NADPH dihydronicotinamide moiety, and NADPH adenine moiety. Subsequently, a cascading protocol that integrated virtual screening and antibacterial test was performed against a biogenic compound library to identify biologically active, subpocket-specific inhibitors. Consequently, five, eight, and six promising compounds for, respectively, subpockets 1, 2, and 3 were selected from the top-100 docking-ranked hits, from which 11 compounds were determined to have high or moderate antibacterial potencies against two reference H. pylori strains, with MIC range between 8 and 93μg/mL. It is found that the HpSDH active site prefers to accommodate amphipathic and polar inhibitors that consist of an aromatic core as well as a number of oxygen-rich polar/charged substituents such as hydroxyl, carbonyl, and carboxyl groups. Subpockets 1- and 2-specific inhibitors exhibit a generally higher activity than subpocket 3-specific inhibitors. Molecular dynamics simulations revealed an intense nonbonded network of hydrogen bonds, π-π stacking, and van der Waals contacts at the tightly packed complex interfaces of active-site subpockets with their cognate inhibitors, conferring strong stability and specificity to these complex systems. Binding energetic analysis demonstrated that the identified potent inhibitors can target their cognate subpockets with an effective selectivity over noncognate ones.

Electron-Selective Epitaxial/Amorphous Germanium Stack Contact for Organic-Crystalline Silicon Hybrid Solar Cells

ABSTRACT: Carrier transport properties can be improved through suppressing the charge carrier recombination and decreasing the contact resistance using the proper carrier-selective contact. In this work, an epitaxial/amorphous germanium (epi/a-Ge) stack thin film is introduced into the rear surface of organic-inorganic hybrid (OIH) solar cells as an efficient electron-selective contact. This novel electron-selective stack contact simultaneously contributes low recombinative and resistive losses through a three-material system composed of n-type silicon (n-Si), epitaxial silicon germanium (epi-SiGe), and amorphous germanium (a-Ge), which promotes the tailoring of band structures, the passivation of surface dangle bond defects and the formation of Ohmic contact. The results result in obvious improvement in the open-circuit voltage (Voc) (from 549.5 mV to 643.0 mV) and fill factor (FF) (from 70.5% to 75.4%), corresponding to the increase in the power conversion efficiency (PCE) of OIH solar cells (from 10.3%...

A coevolution-guided model for the rotor of the bacterial flagellar motor

The Salmonella typhimurium trans-membrane FliF MS ring templates assembly of the rotary bacterial flagellar motor, which also contains a cytoplasmic C-ring. A full-frame fusion of FliF with the rotor protein FliG assembles rings in non-motile expression hosts. 3D electron microscopy reconstructions of these FliFFliG rings show three high electron-density sub-volumes. 3D-classification revealed heterogeneity of the assigned cytoplasmic volume consistent with FliG lability. We used residue coevolution to construct homodimer building blocks for ring assembly, with X-ray crystal structures from other species and injectisome analogs. The coevolution signal validates folds and, importantly, indicates strong homodimer contacts for three ring building motifs (RBMs), initially identified in injectisome structures. It also indicates that the cofolded domains of the FliG N-terminal domain (FliG_N) with embedded α-helical FliF carboxy-terminal tail homo-oligomerize. The FliG middle and C-terminal domains (FliG_MC) have a weak signal for homo-dimerization but have coevolved to conserve their stacking contact. The homodimers and their ring models fit well into the 3D reconstruction. We hypothesize that a stable FliF periplasmic hub provides a platform for FliG ring self-assembly, but the FliG_MC ring has only limited stability without the C-ring. We also present a mechanical model for torque transmission in the FliFFliG ring.