Formation Of Hydrogen Bonds Research Articles

Potential Water Collection From Air by Chloride Perovskites.

Directly capturing water from the air has become a compelling strategy to secure water resources. Yet, challenges persist with sorption-based hygroscopic materials, such as inadequate water adsorption efficiency, material degradation post-adsorption, and the need for energy input during water collection. This study introduces an alternative category of sorbent materials potentially for atmospheric water harvesting-metal chloride perovskites-that exhibit spontaneous water vapor adsorption and liquid water collection. This water uptake capability stems from the uncoordinated polar ions that form hydrogen bonds with water molecules, while the cubic lattice imparts a solid framework ensuring structural stability and inhibiting hydrolysis. The methylammonium lead chloride perovskite pellets exhibit efficient water collection performance, with a record absorption rate of 0.841 L m-2 h-1 and a total water collection of 3.675 L m-2 within a 7-h cycle. This initiative attempts to provide a new material class candidate for the potential application of passive atmospheric water harvesting.

Exploring novel Apalutamide analogues as potential therapeutics for prostate cancer: design, molecular docking investigations and molecular dynamics simulation

Introduction: Prostate cancer (PC) ranks as the second most frequent type of cancer in men and is the fourth largest cause of mortality worldwide. Androgenic hormones such as testosterone and dihydrotestosterone are crucial for the development and progression of the prostate gland. Androgenic hormones bind to androgen receptors (AR) and trigger the synthesis of many genes that stimulate the growth of prostate cells, initiating PC growth. Apalutamide (APL) is a non-steroidal antiandrogen drug used to treat PC; however, it also causes a variety of toxicities and resistance during the treatment.Methods: The purpose of this study was to computationally identify new and safer analogues of APL, focusing on improved pharmacokinetic properties and reduced toxicity. Drug likeness (DL) and drug score (DS) were also calculated. Docking studies on the designed analogues were conducted to predict their binding affinities and compare their orientations with the ligands in the original crystal structure. Molecular dynamics (MD) simulation of docked ligands was done using Schrödinger suite.Results: We generated a total of 1,415 analogues for different groups of APL using the bioisosteric approach. We selected 80 bioisosteres based on pharmacokinetic profiles, DL and DS score predictions, and found that the designed APL bioisosteres were optimal to good compared to APL. Analogues APL19, APL35, APL43, APL76, and APL80, formed hydrogen bonds with protein (PDB ID: 5T8E) which is similar hydrogen bonding to the standard (APL). The MD simulation result confirmed that APL43 and APL80 complexes were stable during the 100 nS run.Discussion: The results suggest that the APL analogues, particularly APL43 and APL80, are predicted to be potential antiandrogen drugs for the treatment of prostate cancer.

Polyelectrolyte mixture enables electrowetting liquid lens with large optical power tuning range

Electrowetting liquid lenses have aroused considerable interest among researchers in a variety of industrial applications and wetting sciences. However, conventional electrowetting liquid lenses face significant limitations in their optical power tuning range due to contact angle saturation. To address this issue, our research introduces a polyelectrolyte mixture (PM) composed of ammonium polyphosphate and potassium chloride, which enables a broad optical power tuning range for electrowetting liquid lenses. Through a comprehensive analysis involving viscosity, Raman spectrum, and contact angle measurements, we offer additional insights into the interdisciplinary mechanism of the PM in enhancing the electrowetting effect. Our investigation elucidates how the conformation of the polyelectrolyte and the formation of hydrogen bonds at varying concentrations can impact the electrowetting gain. By optimizing the electrowetting concentration of the PM (12.5 wt. % ammonium polyphosphate and 7.5 wt. % potassium chloride), we achieve a liquid lens with an extensive tuning range (−37.97 to +18.71 D) at 0–45 V, featuring a substantial aperture (6.4 mm) and a low threshold voltage (10 V). This PM formulation effectively mitigates contact angle saturation, thereby offering promising applications and paving the way for the development of liquid lenses with a significantly enhanced optical power tuning capacity.

Development of New N-{4-[(7-Chloro-5-methylpyrrolo[2,1-f] [1,2,4]triazin-4-yl)oxy]-3-fluorophenyl}benzenesulfonamide Analogues: Exploring Anticancer Potential through MerTK Inhibition

AbstractMer proto-oncogene tyrosine-protein kinase (MerTK), a part of the TAM (TYRO3, AXL, and MerTK) family, is directly correlated with metastasis and various types of cancers. The inhibition of this receptor is a promising strategy for more-effective chemotherapy. Considering the pharmacophoric features of the active domain of MerTK and the structural characteristics of the investigational drug BMS794833, we designed five new N-{4-[(7-chloro-5-methylpyrrolo[2,1-f][1,2,4]triazin-4-yl)oxy]-3-fluorophenyl}benzenesulfonamide analogues. In cytotoxicity studies, one of the analogues displayed a significantly higher cytotoxicity than cisplatin. It showed IC50 values of 2.09, 1.96, and 3.08 μM against A549, MCF-7, and MDA-MB-231 cancer cell lines, respectively. In drug metabolism and pharmacokinetic studies, it was the most stable analogue and displayed a moderate MerTK inhibitory potential. Molecular-docking studies were performed to corroborate the MerTK inhibition, and the same analogue achieved the most significant docking score (–12.33 kcal/mol). Docking interactions demonstrated that the imine and amine group of the 3-chloropyridine moiety of BMS794833 formed hydrogen bonds with the main chain of the ATP pocket residue Met674, while the oxygen atoms of the 4-oxo-1,4-dihydropyridine-3-carboxamide moiety established hydrogen bonds with the Lys619 and Asp741 amino acid residues of the allosteric pocket of MerTK protein. These promising results provide evidence that the N-{4-[(7-chloro-5-methylpyrrolo[2,1-f][1,2,4]triazin-4-yl)oxy]-3-fluorophenyl}benzenesulfonamide pharmacophore can give potential insights into the development of new MerTK inhibitors.

BACE1 inhibitors from the fruits of Alpinia oxyphylla have efficacy to treat T2DM-related cognitive disorder

The fruits of Alpinia oxyphylla (Alpiniae Oxyphyllae Fructus, AOF) are one of the “Four Famous South Medicines” in China. In this study, beta-site amyloid protein precursor cleaving enzyme 1 (BACE1) was applied to explore the active components in AOF responsible for type 2 diabetes mellitus (T2DM)-related cognitive disorder. As a result, 24 compounds including three unreported ones (1, 3, 4) were isolated from AOF. Compound 1 is an unusual carbon‑carbon linked diarylheptanoid dimer, and compound 4 is the first case of 3,4-seco-eudesmane sesquiterpenoid with a 5/6-bicyclic skeleton. Four diarylheptanoids (3, 5–7), one flavonoid (9) and two sesquiterpenoids (14 and 20) showed BACE1 inhibitory activity, of which the most active 6 was revealed to be a non-competitive and anti-competitive mixed inhibitor. Docking simulation suggested that OH-4′ of 6 played important roles in maintaining activity by forming hydrogen bonds with Ser36 and Ile126 residues. Compounds 3, 5, 9 and 20 displayed neuroprotective effects against amyloid β (Aβ)-induced damage in BV2 cells. Mechanism study revealed that compounds 5 and 20 downregulated the expression of BACE1 and upregulated the expression of Lamp2 to exert effects. Thus, the characteristic diarylheptanoids and sesquiterpenoids in AOF had the efficacy to alleviate T2DM-related cognitive disorder by inhibiting BACE1 activity and reversing Aβ-induced neuronal damage.

Highly Hydrophilic TiO2 Nanoparticles as Stabilizers of Pickering Emulsions with Photosensitive Lipophilic Compounds: Synthesis and Application.

Pickering emulsions are a very promising system for encapsulating and photoprotecting active ingredients. The highest photoprotection efficiency can be achieved when bare TiO2 nanoparticles are used as stabilizers. However, the main problem when using highly hydrophilic TiO2 nanoparticles is their inability to adsorb at the oil-water interface. Here, we developed emulsions stabilized by bare, highly hydrophilic TiO2 nanoparticles for the encapsulation and photoprotection of active lipophilic compounds. Emulsion stabilization occurs due to the formation of hydrogen bonds between hydroxyl groups on the particle surface and the carbonyl groups of the oil molecules. The stability and rheological properties of emulsions are explained by the properties of the initial hydrosols. The resulting Pickering emulsions demonstrated effective UV protection of α-lipoic acid. Our results pave the way for the formulation of Pickering emulsions with a widely used cosmetic oil and show for the first time the possibility of photoprotection of a lipophilic active substance using unmodified TiO2 nanoparticles.

Enhanced cation interaction in perovskites for efficient tandem solar cells with silicon.

To achieve the full potential of monolithic perovskite/silicon tandem solar cells, crystal defects and film inhomogeneities in the perovskite top cell must be minimized. We discuss the use of methylenediammonium dichloride as an additive to the perovskite precursor solution, resulting in the incorporation of in situ-formed tetrahydrotriazinium (THTZ-H+) into the perovskite lattice upon film crystallization. The cyclic nature of the THTZ-H+ cation enables a strong interaction with the lead octahedra of the perovskite lattice through the formation of hydrogen bonds with iodide in multiple directions. This structure improves the device power conversion efficiency (PCE) and phase stability of 1.68 electron volts perovskites under prolonged light and heat exposure under 1-sun illumination at 85°C. Monolithic perovskite/silicon tandems incorporating THTZ-H+ in the perovskite photo absorber reached a 33.7% independently certified PCE for a device area of 1 square centimeter.

Competitive Effects of Anions on Protein Solvation by Aqueous Ionic Liquids.

The present study utilizes molecular dynamics simulations to examine how different anions compete for protein solvation in aqueous solutions of ionic liquids (ILs). Ubiquitin is used as model protein and studied in IL mixtures sharing the same cation, 1-ethyl-3-methylimidazolium (EMIM), and two different anions in the same solution, from combinations of dicyanamide (DCA), chloride (Cl), nitrate (NO3), and tetrafluoroborate (BF4). Our findings reveal that specific interactions between anions and the protein are paramount in IL solvation, but that combinations of anions are not additive. For example, DCA exhibits a remarkable ability to form hydrogen bonds with the protein, resulting in a significantly stronger preferential binding to the protein than other anions. However, the combination of DCA with NO3, which also forms hydrogen bonds with the protein, results in a smaller preferential solvation of the protein than the combination of DCA with chloride ions, which are weaker binders. Thus, combining anions with varying affinities for the protein surface modulates the overall ion accumulation through nonadditive mechanisms, highlighting the importance of the understanding of competition for specific interaction sites, cooperative binding, bulk-solution affinity, and overall charge compensations, on the overall solvation capacity of the solution. Such knowledge may allow for the design of novel IL-based processes in biotechnology and material science, where fine-tuning protein solvation is crucial for optimizing performance and functionality.

The evaluation of the interaction of baicalein (5,6,7-trihydroxyflavone) with human IgG and a glioblastoma multiforme (GBM) cell line

Baicalein, a nutritional phenolic bioactive small molecule present in the roots of Scutellaria baicalensis and Scutellaria lateriflora, shows promising therapeutic effects against a wide range of cancer cells. However, its potential binding with blood carrier proteins and its anticancer mechanisms have not been well investigated. In this study, the interaction between baicalein and immunoglobulin G (IgG) was analyzed by analyzing intrinsic fluorescence, ellipticity changes, as well as molecular docking. The anticancer effects of baicalein against a glioblastoma multiforme (GBM) cell line, U87MG, and one normal immortalized human astrocytes were assessed by MTT, real-time PCR, caspase assay, and western blot. It was shown that fluorescence quenching mechanism of human IgG by baicalein was based on a static quenching, where one binding site was responsible for the formation of baicalein-IgG complex derived by the formation of hydrogen bonds and van der Waals forces. Molecular docking study indicated that tyrosine residues (Tyr 91 and Tyr 98) were mostly involved in the binding site of baicalein to IgG. The cellular assay demonstrated that baicalein induced U87MG cell line death with an IC50 concentration of 73.19 µM, whereas normal astrocytes depicted over 82.94 % portion of viability at 100 µM baicalein. The Bax mRNA overexpression, Bcl-2 mRNA downexpression, as well as the elevation of caspase-9 and caspase-3 activities confirmed that baicalein could effectively trigger the apoptosis of U87MG cells. Moreover, it was explored that baicalein downregulated the expression of the Axl/STAT3 signaling pathway in the U87MG cells, which is responsible for cellular proliferation and growth. In conclusion, these data may provide useful information regarding the pharmaceutical application of baicalein.

Enhanced adsorption of Congo red dye by CS/PEG/ZnO composite hydrogel: Synthesis, characterization, and performance evaluation

Hydrogels are 3D interconnected network polymer chains that are hydrophilic, swell in water and imbibe a significant amount of water. When hydrogel absorb water, dye molecules transfer to their surface, aiding adsorption. Adsorption is efficient, cheap, and versatile technique to remove dye from aqueous media. In this study, high-performance adsorbents from chitosan/polyethylene glycol (CS/PEG) hydrogel cross-linked with intermolecular H-bonds and chitosan/polyethylene glycol/ZnO (CS/PEG/ZnO) composite hydrogel cross-linked with Zn2+ were developed by an instantaneous gelation method. The prepared composite hydrogels were characterized by Fourier transform infrared (FTIR) spectroscopy, Scanning electron microscopy (SEM), X-ray diffraction (XRD), thermo-gravimetric analysis (TGA), transmission electron microscopy (TEM) and Zeta-sizer. The developed composite hydrogels effectively adsorbed Congo red (CR) dye from aqueous media. CR adsorption efficiency using adsorbent dosage, contact time, pH and temperature factors were conducted by batch adsorption experiments. The obtained results for CR adsorption equilibrium were compatible with the Langmuir model with maximum adsorption capacity (qmax) of 212.76 mg/g for CS/PEG and 256.41 mg/g for CS/PEG/ZnO composite hydrogel. The qmax was measured at pH 3 and 25 min and kinetic study confirmed that pseudo 2nd order kinetic model was best followed. Thermodynamic study indicated that the nature of the adsorption phenomena was physical, endothermic and spontaneous. The high adsorption efficiency is mainly ascribed to the protonation of –NH2 groups present in CS/PEG and CS/PEG/ZnO composite hydrogels which enhanced its electropositivity. Hydrogen bond formation and electrostatic attraction among adsorbent and dye govern the adsorption mechanism. It can be concluded that CS/PEG hydrogel and CS/PEG/ZnO composite hydrogels could be considered as efficient, beneficial and potential adsorbents for environmental remediation.

Screening of novel disease genes of sepsis-induced myocardial Disfunction by RNA sequencing and bioinformatics analysis

BackgroundThere is still a lack of effective treatment for sepsis-induced myocardial dysfunction (SIMD), while the pathogenesis of SIMD still remains largely unexplained. MethodsRNA sequencing results (GSE267388 and GSE79962) were used for cross-species integrative analysis. Bioinformatic analyses were used to delve into function, tissue- and cell- specificity, and interactions of genes. External datasets and qRT-PCR experiments were used for validation. L1000 FWD was used to predict targeted drugs, and 3D structure files were used for molecular docking. ResultsBased on bioinformatic analyses, ten differentially expressed genes were selected as genes of interest, seven of which were verified to be significantly differential expression. Bucladesine was considered as a potential targeted drug for SIMD, which banded to seven target proteins primarily by forming hydrogen bonds. ConclusionIt was considered that Cebpd, Timp1, Pnp, Osmr, Tgm2, Cp, and Asb2 were novel disease genes, while bucladesine was a potential therapeutic drug, of SIMD.

Impact of surface-active ionic solutions on the structure and function of laccase from trametes versicolor: Insights from molecular dynamics simulations

Many protein-ionic liquid investigations have examined laccase interactions. Laccases are a class of poly-copper oxidoreductases that retain significant biotechnological relevance owing to their notable oxidative capabilities and their application in the elimination of synthetic dyes, phenolic compounds, insecticides, and various other substances. This study investigates the impact of surface active ionic liquids (SAILs), namely, decyltrimethylammonium bromide [N10111][Br] and 1-decyl-3-methylimidazolium chloride [C10mim][Cl] as cationic surfactant ionic liquids and cholinium decanoate [Chl][Dec], an anionic surfactant ionic liquid, on the structure and function of laccase from the fungus Trametes versicolor (TvL) by the molecular dynamics (MD) simulation method. In summary, this study showed that laccase solvent-accessible surface area increased in the ionic liquid [Chl][Dec] while it decreased in the other two ionic liquids. Interestingly, [Chl][Dec] ionic liquid components formed hydrogen bonds with laccase, while [N10111][Br] and [C10mim][Cl] components were unable to form hydrogen bonds with laccase. The quantity of hydrogen bonds formed between water molecules and the enzyme was also diminished in the presence of [Chl][Dec] in comparison to the other two ionic liquids. especially at a concentration of 250 mM. In 250 mM concentrations of [N10111][Br] and [C10mim][Cl], clusters of long-chain cations are likely to form near the copper T1 site. However, even at low [Chl][Dec] concentrations, long [Dec]- chains were observed to penetrate the enzyme near the copper T1 site, and at 250 mM [Chl][Dec], a large cluster of anions occupied the opening of the active site. The results of the analysis also show that the interaction between the [Dec]- anion and the enzyme is stronger than the interaction between [N10111]+ and [C10mim]+ with laccase; in addition, the [Dec]- anion, compared to [Br]- and [Cl]- has a much greater tendency to bind with the enzyme residues.

Significantly enhanced high-temperature energy storage performance for polymer composite films with gradient distribution of organic fillers

Film capacitors as one of the most important electronic devices are heading in large capacity, heightened integration and excellent extreme-condition tolerance, which faces the challenges in maintaining outstanding performance under harsh conditions of high temperature and large electric field. Nonetheless, polymer capacitive films, which are renowned for their exceptional thermal stability, experience an escalation in conduction losses at elevated temperatures, resulting in degradation of energy storage performance. This study presents the gradient distribution of organic fillers content in all-organic polymer capacitive films utilizing electrospinning technique, the significantly improved high-temperature energy storage performance has been achieved. Glucose (GLC), a weak polar molecule rich in hydroxyl groups, is blended with the most promising polyetherimide (PEI). Experimental and theoretical calculations confirm that the formed hydrogen bond between GLC and PEI acts as a trapping site for capturing carriers and suppressing conduction losses. Furthermore, the spatial distribution of organic fillers was designed on the basis of direct mixing. The results demonstrate that the gradient composite film introduces interlayer interfacial polarization, while the dielectric mismatch between adjacent layers increases the height of potential barriers for the charge carriers across the interfaces, thereby achieving a synergistic enhancement of dielectric response and insulation strength. The maximum discharge energy density of 6.52 J/cm3 with an efficiency of 85.6 % has been achieved at 150℃ for the modified capacitive films. This work establishes a decoupling relationship between permittivity and electric breakdown strength, offering insights for the advancement of polymer films with outstanding energy storage capabilities in extreme environments.

Identification of a novel RHCE*Ce (829G > A) allele associated with absence of C and e antigens expression.

The Rh blood group antigens are encoded by the RHD and RHCE genes, which possess a remarkable degree of polymorphism owing to their high homologous structures. These variants of the RH genes can lead to absence or weak expression of antigens. Analysis of RHCE genotyping by Polymerase Chain Reaction (PCR-SSP) method specific to detect c.48G, c.48C, 109 bp insertion of IVS2, c.201A and c.307C and RhCE phenotyping, were conducted in 316 Chinese patients in previous study. One patient with discrepancy typing result was collected for further RhCE serologic typing using microcolumn gel method and tube method in saline using monoclonal antibodies. PacBio sequencing was performed for RHCE, RHD and RHAG complete sequence analysis. 3D molecular models of the protein with the wild-type and mutant residue were generated using the DynaMut web server. The effect of the mutation on the protein function was predicted by PolyPhen-2 software. One male patient of Chinese Han was detected with RHCE*C allele showed by PCR-SSP method but ccEE phenotype. Further PacBio sequencing identified one normal RHCE*cE allele and one RHCE*Ce allele carried a novel c.829G > A (p.Gly277Arg) variant, which the encoded amino acid located in the ninth transmembrane segment of RhCE protein. Crystallisation analysis of 3D molecular models revealed that the substitution at Arg277 leads to the formation of additional hydrogen bonds, including weak hydrogen bonds between multiple atoms. It also results in hydrophobic ion interactions between Arg277 and Ala244. This mutation is predicted to have a damaging effect on protein function. One novel RHCE*Ce allele with c.829G > A (p.Gly277Arg) variant was identified to resulting in the absence or weak expression of C and e antigens.

Dynamic interchange between two protonation states is characteristic of active sites of cholinesterases.

Cholinesterases are well-known and widely studied enzymes crucial to human health and involved in neurology, Alzheimer's, and lipid metabolism. The protonation pattern of active sites of cholinesterases influences all the chemical processes within, including reaction, covalent inhibition by nerve agents, and reactivation. Despite its significance, our comprehension of the fine structure of cholinesterases remains limited. In this study, we employed enhanced-sampling quantum-mechanical/molecular-mechanical calculations to show that cholinesterases predominantly operate as dynamic mixtures of two protonation states. The proton transfer between two non-catalytic glutamate residues follows the Grotthuss mechanism facilitated by a mediator water molecule. We show that this uncovered complexity of active sites presents a challenge for classical molecular dynamics simulations and calls for special treatment. The calculated proton transfer barrier of 1.65 kcal/mol initiates a discussion on the potential existence of two coupled low-barrier hydrogen bonds in the inhibited form of butyrylcholinesterase. These findings expand our understanding of structural features expressed by highly evolved enzymes and guide future advances in cholinesterase-related protein and drug design studies.

NADES systems comprising choline chloride and polyphenols: Physicochemical characterization, antioxidant and antimicrobial activities

Natural Deep Eutectic Solvents (NADES) represent a new group of green and environmentally friendly solvents that comply with all the principles of green chemistry. NADES are formed via hydrogen bonding by combining hydrogen bond donors (HBD) and hydrogen bond acceptors (HBA). In this paper, we presented ten NADES systems based on choline chloride and different polyphenols. The basic physicochemical and biological properties were evaluated (stability, density, viscosity, FTIR, ORAC, antibacterial activity). It was shown that all the systems had a high densities and high dynamic viscosities. The densities ranged from 1.096 – 1.221 mg/mL for ChCl – resveratrol and ChCl – rutin, respectfully. The dynamic viscosities ranged from 0.247 – 1.662 Pa S for ChCl – gallic acid and ChCl – chlorogenic acid, respectfully. The viscosity could be lowered by increasing the molar ratio of choline chloride. Four NADES systems, comprising catechin, rosmarinic acid, gallic acid and chlorogenic acid could be diluted with water without affecting the stability of those systems. This finding could increase the usability of those systems. The FT-IR analysis of the selected systems showed that the peaks are widened and slightly shifted, without formation of new peaks, which proves the formation of hydrogen bonds between the NADES constituents. All tested systems showed high ORAC value (426.94 – 874.96 Trolox eq/mL) and antibacterial activity (0.625 – 2.5 % NADES).

Elucidation of the sweetening mechanism of sweet orange fruit aroma compounds on sucrose solution using sensory evaluation, electronic tongue, molecular docking, and molecular dynamics simulation

Sweetness enhancement through aroma has been suggested as a strategy to mitigate sugar addition in foods, but such enhancement depends on the type of aroma. Ethyl propanoate, ethyl 2-methylbutanoate, octyl acetate, ethyl butanoate, ethyl hexanoate, butyl hexanoate, γ-terpinene, nootkatone, and acetophenone with fruity aroma from sweet orange were selected as the objects to investigate the sweetening effect of aroma compounds in a 5% sucrose solution using an artificial sensory tongue and an electronic tongue. The results showed that nine aroma compounds exerted a significant effect on the sweetness, among which ethyl butanoate, ethyl propanoate, and ethyl 2-methylbutanoate imparted a more comfortable effect. Subsequently, the mechanism of their sweetening action was studied by molecular simulation. Molecular docking results indicated that the binding free energy decreased below -5.9 kcal/mol in the presence of aroma compounds, indicating that sucrose was more tightly docked to the sweet taste receptor. Molecular dynamics (MD) further implied that under the influence of ethyl butanoate, the stable time of binding was advanced by 15 ns, and the amino acids forming hydrogen bonds changed from LYS65, ASP278, GLU302, SER165, and SER303 to SER165, ASP142, LYS65, and GLU302. The interaction depends on hydrogen bonds, water bridges, and hydrophobic forces.

Molecular Docking, Quantum Mechanics and Molecular Dynamics Simulation of Anti-CAD Drugs Against High-Risk Xanthine Dehydrogenase Variants Associated with Oxidative Stress Pathways

Xanthine dehydrogenase (XDH) contributes significantly to generating reactive oxygen species in coronary artery disease (CAD). XDH has been proposed as a therapeutic target, but its genetic variants could affect protein structure and drug response. We aimed to assess protein structure modification occur due to genetic variants and to screen 215 CAD drugs for their utility in personalized CAD treatment against the XDH variants. A series of computational methods were implemented to identify pathogenic variants that cause XDH structure instability localized at the conserved regions contributing to functional significance. Then, the XDH structures with the pathogenic variants were modeled using two different approaches to select the best models for docking with the CAD drugs. Finally, the stability of the docked complexes and their ability to transfer electrons were evaluated using molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculation. Among 751 variants examined; R149C and Q919R showed high pathogenicity, localized in conserved regions could alter protein structure and function. Further, docking of CAD drugs against XDH (native, R149C and Q919R) showed vericiguat with higher affinity, ranging from -7.95 kcal/mol to -10.41 kcal/mol, than the well-known XDH inhibitor (febuxostat, -5.73 kcal/mol to -8.35 kcal/mol). This indicates that vericiguat will be effective in CAD treatment, regardless of the XDH variants. Additionally, MD simulation and QM/MM confirmed vericiguat stability and electron transfer ability to form hydrogen bonds with the XDH protein. In conclusion, vericiguat will be beneficial for the personalized treatment of CAD by inhibiting XDH variants. Additional clinical studies are necessary to confirm our findings.

OBP83b and OBP49a Involved in the Perception of Female-Derived Pheromones in Bactrocera dorsalis (Hendel).

In Bactrocera dorsalis, both males and females release chemical signals to attract mates. In our previous study, we identified ethyl laurate, ethyl myristate, and ethyl palmitate as potent female-derived pheromones that contribute to mate attraction. However, the mechanisms underlying the olfactory recognition remain unclear. In this study, we observed strong antennal and behavioral responses in male B. dorsalis to these female-derived pheromones, and further investigation revealed significant upregulation of OBP49a and OBP83b following exposure to these compounds. Through fluorescence competitive binding assays and RNA interference techniques, we demonstrated the crucial roles of OBP49a and OBP83b in detecting female-derived pheromones. Finally, molecular docking analysis identified key residues, including His134 in OBP83b and a lysine residue in OBP49a, which formed hydrogen bonds with female-derived pheromones, facilitating their binding. These findings not only advance our understanding of olfactory recognition of pheromones in B. dorsalis but also offer potential targets for developing olfaction-interfering techniques for pest control.

MOLECULAR DOCKING ANALYSIS AND ADMET PREDICTION Of Caesalpinia sappan COMPOUNDS AS ANTIINFLAMMATORY THROUGH CYCLOOXYGENASE-2 INHIBITION

Selective COX-2 inhibitors have been considered safer treatments than NSAIDs for inflammation from its side effect. Sappanwood was already known for its antiinflammatory activity, but its selectivity towards COX-2 has not been tested. The purpose of this study was to determine the potential activity of compounds in Caesalpinia sappan as anti-inflammatory agents by inhibiting COX-2 and determine their ADMET’s properties through in silico study. Qulified compound from Lipinski’s rule of five evaluation would be continued to the molecular docking using Autodock Tools and ADMET prediction using SwissADME and ADMETLab. Three compounds known to have the best free bond energy (ΔG) values were Caesalpiniaphenol A, Sappankalkon, and Deoxysappanone B with ΔG values respectively (-9.36 ; -9.23 ; -9.02 kcal/mol) and their inhibition constant values of (124.44 ; 172.43 ; 244.75 nM) respectively. Amino acid residues that are known to involve to the formation of hydrogen bonds in ligands are GLN 192 and PHE518. Toxicity results showed that these three compounds were predicted to be neither hepatotoxic nor hERG inhibitors, but 3-deoxysappanone B and sappankalkon was predicted to cause AMES mutagenicity and skin sensitivity. It can be concluded that these third compound has the potential as an inhibitor of the COX-2 enzyme.