Molecular Calculations Research Articles

Synthesis of Novel Derivatives of 4,6-Diarylpyrimidines and Dihydro-Pyrimidin-4-one and In silico Screening of Their Anticancer Activity

: Derivatives of pyrimidinone, dihydropyrimidinone, and 2,4-diaryl-substituted pyrimidines were synthesized by cyclocondensation of α-aminoamidines with various sat-urated carbonyl derivatives and their analogs. The therapeutic potential of the newly syn-thesized derivatives for cancer treatment was evaluated using molecular docking calcula-tions. The molecular docking results indicate that some of the synthesized diaryl deriva-tives of pyrimidine exhibit high binding affinity towards PIK3γ. Aim and Objective: 4,6-Diaryl-substituted pyrimidines have shown high inhibitory poten-cy against phosphoinositide 3-kinases (PI3Ks), which are important targets in oncology. Inhibition of PI3Ks could potentially be a viable therapy for human cancers. Materials and Methods: The synthesis of pyrimidinone and dihydropyrimidinone deriva-tives as well as a series of 2,4-diaryl-substituted pyrimidines were described. These com-pounds were synthesized by cyclocondensation of α-aminoamidines with various saturated carbonyl derivatives and their analogs. Results: Derivatives of pyrimidinone, dihydropyrimidinone, and 2,4-diaryl-substituted py-rimidines were synthesized by combining α-aminoamidines with various saturated car-bonyl derivatives and their analogs. By adjusting the large substituents in the 2-position, we gained the ability to modify the therapeutic properties of the resulting compounds. The potential of the newly synthesized derivatives for cancer treatment was assessed using mo-lecular docking calculations. The results of the docking calculations suggest that some of the synthesized diaryl derivatives of pyrimidine have a strong binding affinity towards PIK3γ, making them promising candidates for the development of new anticancer medica-tions. Conclusion: We synthesized some pyrimidinones, dihydropyrimidinones, and 2,4-diaryl-substituted pyrimidines by combining α-aminoamidines with various saturated carbonyl derivatives and similar compounds. Molecular docking results suggest that certain diaryl derivatives of pyrimidine have a strong binding affinity for PIK3γ. Moreover, diphenyl de-rivatives of pyrimidine exhibited dual inhibitory activity against PI3K and tubulin, show-ing promise for the development of next-generation microtubule-targeting agents for use in combination therapies.

A Molecular Engineering Approach to Conformationally Regulated Conductance Dualism in a Molecular Junction

AbstractOne key aspect for the development of functional molecular electronic devices is the ability to precisely tune and reversibly switch the conductance of individual molecules in electrode‐molecule‐electrode junctions in response to external stimuli. In this work, we present a new approach to access molecular switches by deliberately controlling the flexibility in the molecular backbone. We here describe two new conductance switches based on bis(triarylamines) that rely on the reversible toggling between two conformers, each associated with vastly different conductances. By molecular design, we were able to realize an on/off ratio Ghigh/Glow of ~103, which is one of the largest values reported to date. Flicker noise analysis and molecular transport calculations indicate that on/off switching relies on a change of the conduction pathway and vast differences in molecule‐electrode coupling. We thereby provide a new scaffold for further development of molecular conductance switches that are both efficient and easily refined.

Discovery of novel VEGFR2 inhibitors against non-small cell lung cancer based on fingerprint-enhanced graph attention convolutional network

Despite the proven inhibitory effects of drugs targeting vascular endothelial growth factor receptor 2 (VEGFR2) on solid tumors, including non-small cell lung cancer (NSCLC), the development of anti-NSCLC drugs solely targeting VEGFR2 still faces risks such as off-target effects and limited efficacy. This study aims to develop a novel fingerprint-enhanced graph attention convolutional network (FnGATGCN) model for predicting the activity of anti-NSCLC drugs. Employing a multimodal fusion strategy, the model integrates a feature extraction layer that comprises molecular graph feature extraction and molecular fingerprint feature extraction. The performance evaluation results indicate that the model exhibits high accuracy and stability in predicting activity. Moreover, we explored the relationship between molecular features and biological activity through visualization analysis, thus improving the interpretability of the approach. Utilizing this model, we screened the ZINC database and conducted high-precision molecular docking, leading to the identification of 11 potential active molecules. Subsequently, molecular dynamics simulations and free energy calculations were performed. The results demonstrate that all 11 aforementioned molecules can stably bind to VEGFR2 under dynamic conditions. Among the short-listed compounds, the top six exhibited satisfactory inhibitory activity against VEGFR2 and A549 cells. Especially, compound Z-3 displayed VEGFR2 inhibitory with IC50 values of 0.88 μM, and anti-proliferative activity against A549 cells with IC50 values of 4.23 ± 0.45 μM. This approach combines the advantages of target-based and phenotype-based screening, facilitating the rapid and efficient identification of candidate compounds with dual activity against VEGFR2 and A549 cell lines. It provides new insights and methods for the development of anti-NSCLC drugs. Furthermore, further biological activity tests revealed that Z1-Z3 and Z6 manifested relatively strong antiproliferative activities against NCI-H23 and NCI-H460, and relatively low toxicity towards GES-1. The hit compounds were promising candidates for the further development of novel VEGFR2 inhibitors against NSCLC.

Examining the Impact of 3D Multi-Arm Small Molecules on PM6 : Y6 Blend Reveals the Key Requirements for Their Electronic Properties.

While the emergence of PM6 : Y6 active layer re-energized the organic photovoltaic community, excessive aggregation of Y6 molecules induced by their strong intermolecular interactions has limited the performance of PM6 : Y6-based organic solar cells (OSCs). Adding 3D multi-arm small-molecule acceptors is an effective strategy to inhibit such aggregation. However, to maximize OSC efficiency, these molecules should also contribute to the electronic processes. Here, by taking a benzotriazole-based 3D four-arm small molecule (i.e., SF-BTA1) as representative example, we combine molecular dynamics simulations and density functional theory calculations to examine the molecular-scale impact of 3D multi-arm small molecules on morphological characteristics (especially at the nanoscale) and electronic properties of PM6 : Y6 blends. By considering the intermolecular packing distances, density, and patterns among PM6, Y6, and SF-BTA1 components, exciton transfer rates from SF-BTA1 to Y6 or PM6, charge transfer rates from Y6 or PM6 to SF-BTA1, electron/hole transfer rates among adjacent Y6/PM6 pairs, and radiative and non-radiative recombination processes, we draw a comprehensive picture that describes how 3D multi-arm small molecules improve morphological and electronic properties of PM6 : Y6 blends and thus the OSC efficiency. Furthermore, successful rationalization of these aspects allows us to point out key requirements regarding the electronic properties of 3D multi-arm small molecules.

Computational and In vitro Elucidation of Indolenine-barbituric Acid Zwitterions as Potential Chemotherapeutical Agents

Introduction: The continuous pursuit of novel chemotherapeutical agents with improved efficacy and reduced adverse effects remains a critical area of research despite advancements in chemotherapy. We have previously synthesized indolenine and barbituric acid zwitterion scaffolds 1–10 sustainably; however, their precise chemotherapeutical properties are still lacking. Methods: In this present work, we conducted in silico ADMET analyses, molecular docking calculations, DNA binding studies, and cytotoxicity assays on these zwitterions. Results and Discussion: Among the 10 zwitterions, zwitterion 3 bearing a methoxy group demonstrated the highest drug-likeness score, low toxicity, as well as no violation of Lipinski’s rule of five and Veber’s rule. Both molecular docking calculations and DNA binding studies suggested that the minor groove of DNA is the most probable molecular target of 3 among the others (i.e., topoisomerase and tubulin). In addition, zwitterion 3 exhibited selective cytotoxicity against a wide array of human cancer cell lines without noticeable effect against the normal human colon fibroblast CCD- 18Co. Conclusion: Overall, these preliminary findings from our combined computational and experimental strategy suggested that 3 remains promising for further elaboration as a chemotherapeutic agent.

Lapachol, a natural food component, interacts with human serum albumin: Insights of its impact on the pharmacokinetics of clinically used drugs

Lapachol (LAP), a natural 1,4-naphthoquinone used in popular medicine of South American, is an antioxidant and antimicrobial compound used as a food additive; however, its interactive profile with the main protein carrier of compounds in the human bloodstream (human serum albumin, HSA) was not still characterized. Additionally, the impact of LAP in binding clinically drugs to albumin is still unknown. Thus, the present work describes the interaction HSA:LAP using different biophysical techniques, i.e., 1H saturation-transfer difference nuclear magnetic resonance (1H STD-NMR), isothermal titration calorimetry (ITC), steady-state and time-resolved fluorescence measurements combined with molecular docking calculations. LAP interacts with subdomain region IIA (site I), mainly driven by enthalpy effects, while subdomain region IB (site III) was identified as the second binding site, mainly driven by entropy effects. The binding is spontaneous, strong (binding constant average, Kaverage ≈ 4.45 × 105 M−1), and there is a positive cooperativity in the presence of ibuprofen, with the LAP structure fully buried into the protein cavities. Overall, LAP might impact the residence time (pharmacokinetic profile) of drugs that bind to subdomains regions IIA and IB of albumin, e.g., warfarin, phenylbutazone, diflunisal, naproxen, camptothecin, doxorubicin, daunorubicin, suramin, and tyrosine kinase inhibitors.

Computational Studies and Antimicrobial Activity of 1-(benzo[d]oxazol-2- yl)-3,5-diphenylformazan Derivatives.

Due to the biological importance of the benzoxazole derivatives, some 1- (benzo[d]oxazol-2-yl)-3,5-diphenyl-formazans 4a-f were synthesized and screened for in-silico studies and in-vitro antibacterial activity. The benzo[d]oxazole-2-thiol (1) was prepared by reacting with 2-aminophenol and carbon disulfide in the presence of alcoholic potassium hydroxide. Then 2-hydrazinylbenzo[d] oxazole (2) was synthesized from the reaction of compound 1 with hydrazine hydrate in the presence of alcohol. Compound 2 was reacted with aromatic aldehydes to give Schiff base, 2-(2- benzylidene-hydrazinyl)benzo[d]oxazole derivatives 3a-f. The title compounds, formazan derivatives 4a-f, were prepared by a reaction of benzene diazonium chloride. All compounds were confirmed by their physical data, FTIR, 1H-NMR, and 13CNMR spectral data. All the prepared title compounds were screened for in-silico studies and in-vitro antibacterial activity on various microbial strains. Molecular docking against the 4URO receptor demonstrated that molecule 4c showed a maximum dock score of (-) 8.0 kcal/mol. MD simulation data reflected the stable ligand-receptor interaction. As per MM/PBSA analysis, the maximum free binding energy of (-) 58.831 kJ/mol was exhibited by 4c. DFT calculation data confirmed that most of the molecules were soft molecules with electrophilic nature. The synthesized molecules were validated using molecular docking, MD simulation, MMPBSA analysis, and DFT calculation. Among all the molecules, 4c showed maximum activity. The activity profile of the synthesized molecules against tested micro-organisms was found to be 4c>4b>4a>4e>4f>4d.

Biochar for sustainable agriculture: Improved soil carbon storage and reduced emissions on cropland

Climate change, driven by excessive greenhouse gas (GHG) emissions from agricultural land, poses a serious threat to ecological security. It is now understood that significant differences exist in the responses of soil GHG emissions and soil carbon (C) sequestration to the application of different C-based materials (i.e., straw, organic manure (OM), and biochar). Therefore, elucidating the mechanisms by which differences in the properties of these materials affect soil GHG emissions is essential to comprehensively investigate the mechanisms through which variations in material properties influence soil GHG emissions. Herein, we conducted a field experiment to evaluate the responses of soil GHG emissions to cropland application of different C-based materials and employed molecular modeling calculations to explore the mechanisms by which differences in the properties of these materials affect soil GHG emissions. The results showed that biochar demonstrated superior resistance to biochemical decomposition and soil GHG adsorption capacity, leading to a significant reduction in soil GHG emissions due to its excellent physicochemical properties. The active surface properties of straw and OM enhanced their interaction with decomposing enzymes and accelerated their biochemical decomposition. Wheat-maize rotation with biochar application reduced CO2 emissions by 1089.8 kg CO2eq ha-1 and increased soil organic carbon by 141.8% compared to the control after one year. Collectively, these results contribute to the optimization of cropland application strategies for crop residues to balance soil C sequestration and soil GHG emissions, and to ensure sustainable agriculture and ecological security.

Recent Advancements in Bioelectronic Medicine: A Review.

Bioelectronic medicine is a multidisciplinary field that combines molecular medicine, neurology, engineering, and computer science to design devices for diagnosing and treating diseases. The advancements in bioelectronic medicine can improve the precision and personalization of illness treatment. Bioelectronic medicine can produce, suppress, and measure electrical activity in excitable tissue. Bioelectronic devices modify specific neural circuits using electrons rather than pharmaceuticals and uses of bioelectronic processes to regulate the biological processes underlining various diseases. This promotes the potential to address the underlying causes of illnesses, reduce adverse effects, and lower costs compared to conventional medication. The current review presents different important aspects of bioelectronic medicines with recent advancements. The area of bioelectronic medicine has a lot of potential for treating diseases, enabling non-invasive therapeutic intervention by regulating brain impulses. Bioelectronic medicine uses electricity to control biological processes, treat illnesses, or regain lost capability. These new classes of medicines are designed by the technological developments in the detection and regulation of electrical signaling methods in the nervous system. Peripheral nervous system regulates a wide range of processes in chronic diseases; it involves implanting small devices onto specific peripheral nerves, which read and regulate the brain signaling patterns to achieve therapeutic effects specific to the signal capacity of a particular organ. The potential for bioelectronic medicine field is vast, as it investigates for treatment of various diseases, including rheumatoid arthritis, diabetes, hypertension, paralysis, chronic illnesses, blindness, etc.

Exploration of marine natural compounds as promising MDM2 inhibitors for treating triple-negative breast cancer: insights from molecular docking, ADME/T studies, molecular dynamics simulation and MM-PBSA binding free energy calculations

Triple-negative breast cancer (TNBC), the most aggressive form of breast cancer, presents a significant mortality risk owing to its elevated potential for metastasis. The overexpression of Murine Double Minute 2 homolog (MDM2) protein, a key suppressor of tumour suppressor p53, in TNBC amplifies its growth, advancement, and invasiveness. Thus, inhibiting MDM2 protein emerges as a compelling strategy to enhance the efficacy of TNBC treatment. We aimed to identify novel potential MDM2 inhibitors from natural marine compounds, known for their distinctive chemical structures and heightened anticancer activities, utilizing molecular docking, ADME/T analysis, molecular dynamics (MD) simulations, MM-PBSA calculations, and in silico PASS predictions. A marine compound library was constructed for initial screening purpose and the molecular docking analysis revealed that two marine compounds, namely 10,11-dihydrosodwanone B and sodwanone T, exhibited significantly higher binding affinity (− 9.6 kcal/mol and − 9.1 kcal/mol, respectively) compared to the established inhibitor nutlin-3a (− 8.4 kcal/mol). ADME/T investigations were conducted to ensure the drug-likeness properties and safety of these compounds. Additionally, in silico PASS tool predicted that both compounds possess a heightened potential for anticancer activities. Molecular dynamics simulations (100 ns) and MM-PBSA calculations indicated that sodwanone T formed a relatively more stable complex and had a higher binding-free energy with MDM2, respectively. In conclusion, this research suggests sodwanone T as a promising candidate for further testing and development as an MDM2 inhibitor for potential therapeutic applications against TNBC. Nevertheless, substantial experimental and clinical investigations are necessary to enhance its applicability in clinical settings.Graphical abstract

Hypothermia Exposes Hidden Epitopes in Influenza A Hemagglutinin and Potentiates the Binding of Neutralizing Antibodies

AbstractInfluenza viruses are an important cause of human morbidity and mortality. Influenza uses hemagglutinin, a trimeric surface protein whose monomers are composed of a head and a stalk domain, for immune evasion and cell entry. As the head domain is under constant antigenic drift, eliciting neutralizing antibodies through vaccination against its evolutionarily more conserved stalk domain is a key goal in the treatment of this infection. It is unknown how temperature affects the formation of hemagglutinin‐antibody complexes, particularly with respect to temperatures relevant for the human respiratory tract. Using molecular dynamics simulations and free energy calculations, we determined that bending of hemagglutinin's head domains, an initial step in the process of cell attachment, is present at hypothermia (36 °C), but not at higher temperatures. These conformational changes lead not only to exposure of new epitopes in its stalk domains, but also to enhanced binding of a neutralizing antibody.

Flavin-Mediated Reductive Deiodination: Conformational Events and Reactivity Pattern in the Active Site of Human Iodotyrosine Deiodinase.

Human iodotyrosine deiodinase (hIYD) catalyzes the reductive deiodination of iodotyrosine using a flavin mononucleotide cofactor to maintain the iodine concentration in the body. Mutations in the hIYD gene are linked to human hypothyroidism, emphasizing its role in thyroid function regulation. The present work employs microsecond-scale molecular dynamics simulations and quantum chemical calculations to elucidate the conformational dynamics and reactivity in the active site at various stages of hIYD enzymatic cycle. The flavin is found to employ a unique butterfly motion of its isoalloxazine ring accompanied by a novel active-and-resting state of its ribose 2'-OH group at different stages of the enzymatic cycle. The flavin dynamics are found to control substrate binding affinity, the active site lid closure, and NADPH recognition. The predicted hIYD model shows enhanced stabilization of NADPH due to additional interactions with the N-terminal and intermediate domains. The enzyme uses a group of basic residues (R100, R101, R104, K182, and R279) to stabilize flavin in different stages of catalysis, suggesting potential mutations to control enzyme activity. The reactivity descriptors and stereoelectronic analysis predict the N5 nitrogen of flavin as a proton source during the reductive deiodination, while the anisotropic charge distribution on the halogen atom has negligible structural and electronic effects. The present findings provide key insights into the molecular basis of hIYD activity and lay the groundwork for future research aimed at therapeutic interventions and industrial applications.

Theoretical study of the synergistic effect between glyceryl monooleate lubricant and carboxymethylcellulose in reducing the coefficient of friction of water-based drilling fluids.

Drilling fluids must reduce the coefficient of friction between the drilling equipment and the drilled rock or well casing. Friction forces become particularly relevant in drilling with a high angle gain, in which cases oil-based fluids are generally used. The latter are highly lubricating, but harmful to the environment. For environmental and economic reasons, there is great interest in the development of new additives that enable the use of water-based drilling fluids in all phases of well drilling. Preliminary experimental results show that there is a synergistic effect between glyceryl monooleate (GMO), normally used as lubricant additive, and carboxymethyl cellulose (CMC), a polysaccharide normally used in water-based drilling fluids as a rheological modifier, resulting in extremely low friction coefficients. This work aimed to clarify, through theoretical calculations, the interaction between CMC and GMO, as well as their role in reducing the coefficient of friction between the drilling equipment and the drilled rock when added to water-based fluids. Calculations based on density functional theory (DFT) were used to predict which, CMC or GMO, preferentially binds to the metal surface. The interactions between the polysaccharide and the surfactant were studied through a combination of classical molecular dynamics and DFT calculations. Finally, dynamic calculations were carried out involving fragments of the polysaccharide, the surfactant and hematite (Fe2O3) representing the metal surface, since in the experimental conditions the metal surface will be covered by a primary oxide layer. The results pointed to the preferential binding of CMC to hematite. Regarding the interaction between polymer and surfactant, it was found that the polar part of the GMO interacts with the CMC through hydrogen bonds while the nonpolar carbon chain remains close to the polymer due to hydrophobic interactions. Molecular dynamics calculations showed that GMO increases the binding energy of CMC to hematite and also that this increase in the binding energy is highly influenced by electrostatic interactions.

The presence of NSAIDs may affect the binding capacity of serum albumin to the natural products hymecromone and umbelliferone

The natural products 7-hydroxycoumarin (7HC) and 7-hydroxy-4-methylcoumarin (7H4MC), known as umbelliferone and hymecromone, respectively, are one of the simplest structural examples from coumarin's family, showing several biological activities. Bovine serum albumin (BSA) is the main model protein used in laboratory experiments to characterize the biophysical capacity of potential drugs to be carried until the target in the bloodstream. Thus, the interaction BSA:7HC and BSA:7H4MC was biophysically characterized by circular dichroism (CD), steady-state, and time-resolved fluorescence techniques combined with molecular docking calculations via cross-docking approach to better correlate with the biological medium. There is a ground-state association BSA:7HC/7H4MC, and the presence of the methyl group in the coumarin core did not change the binding affinity and trend to BSA significantly. However, comparing the obtained data with those reported to benzo-α-pyrone there is evidence that the incorporation of the hydroxyl group in the aromatic ring A of the coumarin core improves the binding affinity to albumin around 10-folds and changes the binding site from subdomain IIA to IIIA or IB. In addition, the presence of other drugs, e.g., naproxen or ketoprofen, might interfere with the binding capacity of 7HC and 7H4MC, resulting in perturbations on the residence time of some clinically used drugs in the bloodstream.

Exploring phytoconstituent for confronting the symptoms of polycystic ovarian syndrome: molecular dynamics simulation, quantum studies, free energy calculations and network analysis approaches

Women of the current citizenry are majorly afflicted with gonadal hormonal fluctuations and stress, which play a predominant role in the occurrence and prevalence of PCOS. Synthetic medications under use influence in varietal adverse reactions, hence incorporation of herbs remains a critical part of the therapy. The present study includes selection of phytoconstituents from herbs related to uterine activity and subjection to in silico approach. The constituents were incorporated into a flow of molecular docking, ADMET analysis, toxicity, biological activity prediction, DFT studies, Molecular dynamics, free energy calculations, and network analysis. Three proteins namely Human androgen receptor (2AM9), Human progesterone (1E3K), and Estrogen receptor (1X7R) were selected and used throughout the study. From docking studies, Sarsasapogenin (SAR), β-sitosterol (BES), and Stigmasterol (STI) showed good binding energy interactions with all three proteins, and they also possess ideal drug-likeliness properties with acceptable toxicity profiles. Further analysis by Density functional theory proves they possess considerable intermolecular charge transfer. The insights from Molecular dynamics studies and free energy calculation explain, that Sarsasapogenin (SAR) among the three has strong stability and intermolecular interactions with the findings through network analysis justifying the selection of three proteins. Hence, on the compilation of results, Sarsasapogenin from Asparagus racemosus is determined to be potent and active with all three receptors together that majorly influence in the pathophysiology of the disorder. Further experimental evaluation of SAR in pre-clinical and clinical models would help emphasize the biological activity of the constituent in the management of PCOS.

Hydrogen Gas Sensing Performance of Iron Oxide‐Decorated Carbon Nanotubes: The Influence of Iron Oxide Species and Concentration

In this study, a solvothermal method was used to synthesize a composite of iron oxide nanostructures on carbon nanotubes (CNTs), which was applied as a resistive sensor for hydrogen gas (H2) detection. The nanocomposite was produced with three different iron oxide concentrations (Fe1@CNT, Fe2@CNT, and Fe3@CNT) to investigate the effect of iron species on CNTs and their interaction with hydrogen. Electron microscopy revealed that increasing iron oxide content led to the deterioration of the CNT walls. Raman and FTIR spectra confirmed the predominant presence of α‐Fe2O3 (hematite) on the CNTs, while XPS analysis verified the presence of multiple iron oxides species. High‐resolution XPS of the Fe 2p region indicated the existence of Fe3O4 (magnetite), Fe2O3 (hematite), and FeO (iron(II) oxide) associated with the CNTs. The sample with the lowest iron oxide concentration (Fe1@CNT) showed a 45% sensor response to hydrogen in a dry air atmosphere and the longest recovery time, suggesting a stronger interaction between hydrogen and the nanocomposite. Molecular dynamics simulations and density functional theory calculations further revealed that the presence of iron oxide on the CNT surface significantly altered its electronic properties, particularly by introducing more electronic states near the Fermi level, which enhanced electronic exchange between H2 and the carbon nanotube containing iron oxide.

Unraveling the mechanisms of anammox coupled process with thiosulfate-driven denitrification: Community succession and substrate competition

Thiosulfate-driven denitrification coupled with anammox (TDDA) has garnered interest for its efficient and innovative nitrogen removal capabilities. However, the intricate dynamics of the internal microbial community and the specific characteristics of anaerobic ammonium oxidizing bacteria (AnAOB) remain incompletely understood. This study combines experimental methods with density functional theory (DFT) calculations to address these gaps. The TDDA reactor was successfully started-up with an optimal S2O32--S/NO3−-N ratio of 0.6, achieving a nitrogen removal efficiency of 89.6%. Throughout this process, the relative abundance of Candidatus Kuenenia decreased by 10.2%, while the relative abundance of Candidatus Brocadia increased by 9.6%. The elevated concentration of NO₃--N inhibited Candidatus Kuenenia, and simultaneously stimulated the secretion of extracellular polymers, affecting Fe uptake by Candidatus Kuenenia. To further elucidate substrate competition, molecular docking simulations and DFT calculations were employed. The binding energy, compared with the electrostatic potential energy of the protein pocket, clearly demonstrated that Nir in AnAOB has a higher affinity for the substrate (EAnAOB = −163.2 kJ/mol vs. ESOB = -77.7 kJ/mol). By integrating molecular dynamics insights, this study overcomes experimental limitations and deepens the understanding of the mechanisms within the TDDA system.

Precise Modification of Organic Cations to Enhance the Moisture Stability and Luminescence Efficiency of Mn-Based Halides.

Eco-friendly organic-inorganic hybrid metal halides (OIMHs) are widely recognized as promising candidates for next-generation semiconductor materials. However, achieving inherent moisture stability in OIMHs remains a significant challenge due to the highly hygroscopic nature of the halide structures. In response, a strategy to precisely modify the organic cation (18-ACE: 4,13-diaza-18-crown 6-ether) was developed by introducing hydrophobic benzyl groups into 18-ACE, forming a protective layer that enhances the moisture stability of the OIMHs. Specifically, benzyl groups were incorporated into 18-ACE to create 18-ACE-Bn, which was then used as an organic component to construct zero-dimensional Mn-based (18-ACE)MnBr4 and (18-ACE-Bn)MnBr4·H2O, exhibiting photoluminescence quantum yields (PLQYs) of 68.18% and 97.17%, respectively. Notably, (18-ACE-Bn)MnBr4·H2O demonstrates exceptional moisture stability compared to (18-ACE)MnBr4, retaining 97% of its initial PLQY even after 180 days of exposure to 70% relative humidity. Molecular dynamics and density functional theory calculations indicate that this superior stability is attributed to the terminal benzyl groups embedded within the inorganic framework, forming a compact structure with abundant weak interactions. Leveraging the unique spectral characteristics of (18-ACE-Bn)MnBr4·H2O, a high-performance WLED with a wide color gamut of 125.2% NTSC (National Television Standard Committee) was developed, highlighting its potential for backlight display applications.

GPU Acceleration of the Boys Function Evaluation in Computational Quantum Chemistry

ABSTRACTThe Boys function, a mathematical integral function, plays a pivotal role and is frequently evaluated in ab initio molecular orbital computations. The main contribution of this paper is to accelerate the bulk evaluation of the Boys function through the effective utilization of GPUs. The proposed GPU implementation addresses GPU‐specific programming issues such as warp divergence and coalesced/stride access to global memory, and we employ the optimal numerical evaluation method from four methods based on input values to ensure efficient computation with sufficient accuracy. Moreover, to consider actual computation of molecular integrals, we have implemented and evaluated the proposed method in two scenarios: single evaluation, which computes a single value of the Boys function for a single input, and incremental evaluation, which computes multiple values of the Boys function incrementally. The execution time of the proposed GPU implementation was evaluated for both scenarios using an NVIDIA A100 Tensor Core GPU. As a result, the GPU‐accelerated bulk evaluation has achieved a throughput of computing the values of the Boys function times per second for the single evaluation and times per second for the incremental evaluation, respectively. Our parallelized CPU and GPU implementation is available at https://github.com/sstsuji/Boys‐function‐GPU‐library.

A revised view of the role of CaMKII in learning and memory.

The Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII) plays a fundamental role in learning and possibly also in memory. However, current mechanistic models require fundamental revision. CaMKII autophosphorylation at Thr286 (pThr286) does not provide the molecular basis for long-term memory, as long believed. Instead, pThr286 mediates the signal processing required for induction of several distinct forms of synaptic plasticity, including Hebbian long-term potentiation and depression and non-Hebbian behavioral timescale synaptic plasticity. We discuss (i) the molecular computations by which CaMKII supports these diverse plasticity mechanisms, (ii) alternative CaMKII mechanisms that may contribute to the maintenance phase of LTP and (iii) the relationship of these mechanisms to behavioral learning and memory.