Molecular Calculations Research Articles

Unraveling the metabolic activities of bioactive compounds on cellular models of hepatosteatosis and adipogenesis through docking analysis with PPARs.

Obesity is associated with fatty liver disease. Available therapies show modest efficacy, and nutraceuticals with good effectiveness and safety are largely investigated. We focused on five natural compounds, three plant phenolic compounds (carvacrol, rosmarinic acid, silybin), and two thyroid hormones (T2: 3,5-diiodo-l-thyronine; T3: 3,5,3'-triiodo-L-thyronine) as comparison, to assess their beneficial effects on two cellular models of hepatosteatosis and adipogenesis. All compounds ameliorated the lipid accumulation and oxidative stress in both models, but with different potencies. The peroxisome proliferator-activated receptors (PPARs) are pivotal controllers of adipogenesis and lipid metabolism. For the main isoforms, PPARγ and PPARa, we assessed their possible binding to the compounds by molecular docking calculations, and their expression pattern by real-time PCR. All compounds bind both PPARs with different affinity, while not all compounds affect their expression. The results may clarify the distinctive molecular mechanisms underlying the action of the five compounds in the different cell models with possible applications to treat obesity.

Rapid oxidation of phenolic compounds by O3 and HO●: effects of the air–water interface and mineral dust in tropospheric chemical processes

Abstract. Environmental media affect the atmospheric oxidation processes of phenolic compounds (PhCs) released from biomass burning in the troposphere. To address the gaps in experimental research, phenol (Ph), 4-hydroxybenzaldehyde (4-HBA), and vanillin (VL) are chosen as model compounds to investigate their reaction mechanism and kinetics at the air–water (A–W) interface, on TiO2 mineral aerosols, in the gas phase, and in bulk water using a combination of molecular dynamics simulation and quantum chemical calculations. Of the compounds, Ph was the most reactive one. The occurrence percentages of Ph, 4-HBA, and VL staying at the A–W interface are ∼ 72 %, ∼ 68 %, and ∼ 73 %, respectively. As the size of (TiO2)n clusters increases, the adsorption capacity decreases until n > 4, and beyond this, the capacity remains stable. A–W interface and TiO2 clusters facilitate Ph and VL reactions initiated by the O3 and HO⚫, respectively. However, oxidation reactions of 4-HBA are little affected by environmental media because of its electron-withdrawing group. The O3- and HO⚫-initiated reaction rate constant (k) values follow the order of A–WPh > TiO2 VL > A–WVL > A–W4-HBA > TiO2 4-HBA > TiO2 Ph and TiO2 VL > A–WPh > A–WVL > TiO2 4-HBA > TiO2 Ph > A–W4-HBA, respectively. Some byproducts are more harmful than their parent compounds, so they should be given special attention. This work provides key evidence for the rapid oxidation observed in the O3/HO⚫ + PhC experiments at the A–W interface. More importantly, differences in the oxidation of PhCs by different environmental media due to the impact of substituent groups were also identified.

In vitro, in vivo and in silico anticancer activity and toxicity of Usnic acid extracted from the mycobiont culture of Usneabaileyi.

Lichen has widespread uses in indigenous medicinal traditions, and it has been used to treat various conditions. Among the various active compounds in the lichen, Usnic acid has unique biological activities. However, the toxicology and the mechanism of action of Usnic acid need to be examined in detail to the extent of clinical trials. Hence, the present research is aimed to isolate usnic acid from the mycobiont culture of Usnea baileyi lichen and explore its toxicological properties and those of pharmacological importance. The methanolic extract of these mycobiont cultures has shown the presence of Usnic acid via column chromatography. The Usnic acid was computationally evaluated using molecular docking studies (GLIDE docking) and MMGBSA energy calculations. The results obtained from TLC, LC-MS, UV-VIS spectrophotometer, NMR spectroscopy (1H and 13c), and FT-IR indicated the presence of Usnic acid. An acute toxicity analysis by an in vivo study using a zebrafish animal model showed acute toxicity. The standard disc diffusion and DPPH assay suggested an antimicrobial and antioxidant activity with this lichen compound. The in vitro analysis of Usnic acid in G361 skin cancer cell lines demonstrated its anticancer potential against malignant melanoma. Furthermore, a molecular in silico study returned a good docking score of -7.977, and the MMGBSA free energy was measured as -18 and -30. Therefore, further extensive research on Usnic acid might lead to the development of novel anticancer drugs from the natural sources.

Novel chaotic image cryptosystem based on dynamic RNA and DNA computing

In view of the security problems of image encryption algorithms encoded by single DNA or RNA, to increase the randomness of the diffusion process and the uncertainty of the coding rules, we propose a combining dynamic RNA and DNA computing based chaotic image encryption algorithm, which has a more complicated encryption process for improving the security of the encryption algorithm and increases the difficulty of decoding. First, a new three-dimensional hyperchaotic map is proposed, which exhibits a rich set of dynamic behaviors. Second, the sequences generated by the proposed map are passed to NIST test with good randomness and implemented by digital signal processing hardware, which shows the feasibility of the proposed chaotic map for industrial applications. Second, the K-means algorithm is used to split the plaintext into two parts. Third, the chaotic sequence is used to displace and diffuse the two parts of the plaintext, respectively. Then, chaotic sequences were used to encode using dynamic DNA and RNA of these two parts, respectively. Then, the chaotic sequences were used to compute the dynamic DNA and RNA computing of these two parts, respectively. Finally, the cipher text is decoded accordingly. The experimental results show that compared with some related encryption algorithms, our method has higher security.

Screening of Optimal Phytoconstituents through in silico Docking, Toxicity, Pharmacokinetic, and Molecular Dynamics Approach for Fighting against Polycystic Ovarian Syndrome.

Polycystic ovarian syndrome (PCOS) is a hormonal disorder caused by excessive secretion of male sex hormones in females. Herbal remedies for PCOS are lightning up as they bypass the adverse effects and are profoundly safe on prolonged usage. The present study included a selection of 34 herbs pursuing biological effects on the uterus, and their major chemical constituents were subjected to a series of in silico techniques using different software. The proteins contributing majorly to the hormonal functions like Human cytochrome P450 CYP17A1 (3RUK), Progesterone (1E3K), and estrogen receptor (1X7R) were selected for the study. Molecular docking studies were performed using AutoDock 1.5.7. The pharmacokinetic properties were predicted using the SwissADME online tool, while toxicity parameters were assessed with OSIRIS toxicity explorer and pkCSM. Molecular dynamics simulations and free energy calculations were performed using the Schrödinger suite. Constituents with a basic steroidal nucleus demonstrated high binding energy values. An analysis of all the in silico techniques showed that Sarsasapogenin from Asparagus racemosus exhibited strong binding energies of -10.88 kcal/mol, -10.51 kcal/mol, and -9.79 kcal/mol with the selected specific proteins. In molecular dynamics simulations, Sarsasapogenin displayed ideal stability, with RMSD fluctuations below 3 Å and RMSF slightly higher than the corresponding peak of apoprotein. Additionally, it showed a favorable druglikeness profile and non-toxic effects across all screened parameters. From the list of the selected constituents, sarsasapogenin was found to be ideal, and further research on it for targeting PCOS is expected to yield promising results.

Mechano-responsive fluorescent gel based on tetraphenylethylene-crosslinked dynamic covalent network.

The rapid development of mechano-responsive fluorescence has been driven by its promising applications in the fields of sensors, information encryption, and anti-counterfeiting. However, designing mechanophores that can exhibit fluorescence changes under relatively low force remains challenging. In this study, a mechano-responsive fluorescent gel was developed using a tetraphenylethylene derivative as a cross-linker, producing a dynamic covalent network that exhibits increased fluorescence under tensile stress. Based on controlled experimental studies and molecular modeling calculations, the fluorescence enhancement by external forces was attributed to the restriction of intramolecular motion in tetraphenylethylene by macromolecular chain orientation. In time-dependent experiments, due to the exchange of dynamic covalent bonds, the stress relaxation and the decrease in fluorescence intensity of the gel at fixed strain occurred simultaneously, demonstrating the potential of this fluorescence as an indication of internal stress through aggregation-induced emission (AIE) type mechanophore.

Elucidation of complexation mechanism of rosmarinic acid and berberine

Polyphenols are known to form complexes with various organic compounds. This ability can may change the chemical or physical properties of the compounds involved and may even affect their efficacy in the case of drugs. Our research revealed that mixing solutions of the polyphenol rosmarinic acid (RA) and berberine (Ber), a widely used and pharmacologically important isoquinoline alkaloid, resulted in the formation of a precipitate of the RA–Ber complex at a molar ratio of 1:1. This was confirmed using 1H NMR and Fourier Transform Infrared Spectroscopy. To elucidate the formation mechanism of the precipitate, the behavior of RA and Ber in an aqueous solution was examined using 1H NMR, indicating the formation of the RA–Ber complex at a molar ratio of 1:1, consistent with the results of precipitation. Additionally, we investigated the steric structure of the RA–Ber complex in an aqueous solution using molecular modeling calculations. These calculations suggested the existence of seven types different steric structures of the RA–Ber complex, primarily stabilized by π–π interactions. Based on these results, we concluded that mixing RA and Ber solutions in an aqueous environment results in the formation of RA–Ber complexes with seven types different steric structures at a molar ratio of 1:1. The precipitate forms because these complexes are less water-soluble than either RA or Ber alone.

A Dual Effect Additive Modified Electrolyte Strategy to Improve the Electrochemical Performance of Zinc-Based Prussian Blue Analogs Energy Storage Device.

Prussian blue analogs (PBA) exhibit excellent potential for energy storage due to their unique three-dimensional open framework and abundant redox active sites. However, the dissolution of transition metal ions in water can compromise the structural integrity of PBAs, leading to significant issues such as low cycle life and capacity decay. To address these challenges, we proposed a dual-effect additive-modified electrolyte method to alleviate such issues, introducing sodium ferrocyanide (Na4Fe(CN)6) into aqueous alkaline electrolytes. It could not only capture Zn2+ dissolved on the surface of Na1.86Zn1.46[Fe(CN)6]0.87 (ZnHCF) electrode material during the cycling process but also conduct redox reactions on the electrode surface to provide additional capacitance. Through experiments and molecular simulation calculations, it showed that Na4Fe(CN)6 can restrict the movement of Zn dissolution into the electrolyte on the electrode surface. Based on this, an asymmetric supercapacitor based on ZnHCF//activated carbon was assembled with a modified electrolyte. The assembled supercapacitor displayed a specific capacitance of 1,329.65 mF cm-2, a power density of 2,900 mW cm-2, and an energy density of 388.28 mW h cm-2. This study provides a new idea for the design and construction of stable and efficient PBA energy storage materials by inhibiting the leaching of transition metals in PBA.

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.

Evidence of conformational changes and self-aggregation of 1,2-Bis(4-pyridyl)ethylene in solutions with ethanol

In this work, we report on a concentration and temperature dependent study of the 1,2-Bis(4-pyridyl)ethylene (BPE) – ethanol solutions by means of ultrasonic relaxation spectroscopy. The results revealed two distinct relaxation processes that follow Debye-type frequency dependence. Despite the presence of both processes in the full concentration range studied, the low-frequency relaxation process, related to conformational change between the trans- and gauche-BPE conformers, dominates the acoustic spectra in the low-concentration range, while diminishes at higher concentrations with a parallel enhancement of the high-frequency relaxation process, which is attributed to the self-association of BPE molecules. Quantum mechanical calculations were performed to investigate the energetics of the trans- and gauche-conformers. The trans-species was found more thermodynamically stable than the gauche-conformer. By applying the Synchronous Transit-Guided Quasi-Newton (STQN) methodology, we confirmed the presence of a single transition structure. From the temperature dependence of the acoustic properties, we estimated the activation enthalpy and the enthalpy difference between the two conformers. Density Functional Theory (DFT) calculations have been applied to attain the corresponding enthalpies that were found close to the experimental values. Molecular docking calculations established the self-aggregation mechanism between BPE monomers forming three types of dimeric units, namely the trans-trans, the gauche-gauche and the trans-gauche dimer species with the latter found to be the most thermodynamically favorable. The concentration dependence of the sound velocity, mass density and shear viscosity evidenced the formation of BPE aggregates. From the temperature dependence of the acoustic spectra, the thermodynamic properties of the self-aggregation mechanism of BPE were also determined. Based on the vibrational spectroscopic data, the population of the gauche conformers was found to increase with concentration at the expense of the population of the trans conformers. From the study of the vibrational properties of the system in the short-rage order, we cannot exclude the presence of a specific dimer type in the overall structure. Nevertheless, regarding to the binding score of the trans-gauche dimer (-1.25 kcal/mol), this species is the most thermodynamically stable and most likely its population is higher in dense solutions relative to the other two dimer species.

Enantiomeric C-6 fluorinated swainsonine derivatives as highly selective and potent inhibitors of α-mannosidase and α-l-rhamnosidase: design, synthesis and structure-activity relationship study

Six C-6 fluorinated d-swainsonine derivatives and their enantiomers have been designed based on initial docking calculations, and synthesized from enantiomeric ribose-derived aldehydes, respectively. Glycosidase inhibition assay of these derivatives with d-swainsonine (1) and l-swainsonine (ent-1) as contrasts found that the C-6 fluorinated d-swainsonine derivatives with C-8 configurations as R (α) showed specific and potent inhibitions of jack bean α-mannosidase (model enzyme of Golgi α-mannosidase II); whereas their enantiomers with C-8 configurations as S (β) were powerful and selective α-l-rhamnosidase inhibitors. Molecular docking calculations found the C-6 fluorinatedd-swainsonine derivatives 21, 24 and 25 with highly coincident binding conformations with d-swainsonine (1) in their interactions with the active site of α-mannosidase (PDB ID: 1HWW). Reliability of the docking results were confirmed by Molecular Dynamics (MD) simulation. Additionally, solid interactions with residues Gln-392 and Tyr-393 in the active site of α-l-rhamnosidase (PDB ID: 3W5N) were proved to be vital for potent α-l-rhamnosidase inhibitions of the l-swainsonine derivatives. The role of C-6 fluorines in swainsonine derivatives well demonstrated the “mimic effect” of fluorine to hydrogen by minimal influence on the binding conformations and effective compensation for any possible lost interactions. This work contributes to a comprehensive understanding of the structure-activity relationship (SAR) of the fluorinated swainsonines and ever reported branched swainsonines, and has laid good foundation for development of more potent α-mannosidase and α-l-rhamnosidase inhibitors.

Identification of a Novel HIV‐1 Integrase Strand Transfer Inhibitor: A Synergistic Approach Combining Pharmacophore Modelling and In Vitro Assays

BackgroundAIDS is a highly prevalent and life‐threatening global epidemic that severely compromises the host's immune system, increasing vulnerability to opportunistic diseases. The absence of definitive curative drugs emphasizes the importance and necessity of discovering novel anti‐HIV agents.ObjectiveThis study aims to discover a natural molecular entity that acts as an Integrase strand transfer inhibitor (INSTI) with enhanced potency against HIV.MethodsA ligand‐based pharmacophore model was developed for 4 FDA‐approved INSTIs, with the potential for treating HIV‐1. AutoDock facilitated molecular docking and free energy calculation to discern IN activity. Subsequently, MD simulations assessed interaction stability. ADMET analysis preceded an in vitro anti‐HIV strand transfer assay.ResultsThe generated model revealed a specific interaction involving Mg2+ ion chelation. Crucial residues of HIV‐1 IN and their respective free‐binding energies were identified. The lead compound exhibited superior in silico characteristics which were substantiated by 100 ns MD simulations and MM‐PBSA analysis. Additionally, the in vitro assay demonstrated potent inhibition with the lowest IC50, forming strong molecular interactions with IN.ConclusionThese findings showed valuable insights for the strategic development of new antiretroviral treatments (ART), paving the path for the development of natural therapeutic agents for HIV treatment.

Efficient synthesis and molecular docking of new organoselenium and organosulphur compounds as dual inhibitors for the therapy of Alzheimer's disease as well as Diabetes Mellitus

There are several oxidative stress-related pathways interconnecting Alzheimer's disease and type II diabetes, two public health problems worldwide. Therefore, development of potential multifunctional agents for dual therapy of AD and T2D has received much attention. The present study was aimed to synthesize a new selenocarbonyl and thiocarbonyl compounds and evaluating multifunctional ability of them in the AD and T2D dual therapy. [(PhP(Se)(μ-Se)]2, the selenium counterpart of the well-known sulfur transfer Lawesson's reagent, is a useful reagent for the synthesis of selenocarbonyl compounds. For the conversion of various carbonyl compounds into thiocarbonyl derivatives was formulated by its reaction with LR, [(p-MeOC6H4)P(S)(μ-S)]2. The reactions are carried out under mild conditions and afforded the seleno and thio compounds in good yields. By measuring the newly created compounds' overall antioxidant capacity, iron-reducing ability, and scavenging activity against DPPH and ABTS radicals, they were investigated as antioxidant molecules. Additionally, all the compounds were subjected to further investigation by testing their acetylcholinesterase, α-amylase and α-glucosidase inhibiting activity. According to our findings, the amide derivatives exhibited more promising biological inhibitory actions in comparison to the other compounds. With a total antioxidant capacity (TAC) of 75.11 ± 0.04 mg gallic acid/gm, an iron-reducing power (IRP) of 69.86 ± 0.04 µg/mL, a DPPH radical-scavenging activity (%) of 55.89 ± 0.03 (IC50 = 6.19 ± 0.03 µg/ml), and an ABTS radical-scavenging activity (%) of 61.14 ± 0.03 (IC50 = 4.97 ± 0.06 µg/mL), benzoselenoamide derivative 11b in particular showed the highest antioxidant activities when compared to ascorbic acid. It also affected the activity of acetylcholinesterase through competitive inhibition, which was on par with Donepezil as indicated by in vitro percentage of inhibition 57.44 ± 0.07 % (IC50 = 5.13 ± 0.03 µg/mL). Additionally, it exhibited a comparable level of inhibition to Acarbose in the in vitro percentage of inhibition for α-amylase and α-glucosidase activity, 53.17 ± 0.03 (IC50 = 4.32 ± 0.02) and 42.92 ± 0.03 (IC50 = 2.99 ± 0.02) respectively. Furthermore, molecular docking calculations were made to explain the dual inhibitors for the therapy of Alzheimer's as well as Diabetes Mellitus for all synthesized compounds. In silco docking results revealed that compound 11b were the top docked bioactive compounds against the target proteins (AChE as a cholinergic enzyme and 11-Beta-Hydroxysteroid dehydrogenase-1(11β-HSD1)). After these calculations, ADMET analysis was performed to examine the drug properties of all novel compounds. Overall, the results demonstrated that the organoselenium-based compounds might serve as possible drugs for the therapy of Alzheimer's disease as well as Diabetes Mellitus.

Construction of an electrochemical aptamer-based sensors for rapid quantification of the anticancer drug imatinib in blood to improve drug bioavailability at microdoses

Imatinib (Ima), as a commonly used anticancer drug for the clinical treatment of leukemia and gastrointestinal mesenchymal stromal tumour, requires timely monitoring of patients' blood concentration to ensure efficacy while reducing complications and achieving precision medicine due to its narrow therapeutic window (1–5 μM) and the varying sensitivity and resistance of different patients to Ima. However, traditional assays are slow and cumbersome, so improved and innovative platforms for monitoring Ima in the clinic are necessary. In this work, a nanoporous electrochemical aptamer-based (E-AB) sensor was designed for the detection of Ima and imatinib mesylate (Ima-Mes) in blood. Apt-37, a high-affinity and conformationally variable aptamer, was screened by molecular docking simulation calculations and circular dichroism (CD) for the construction of the E-AB sensor. The sensor detected Ima and Ima-Mes in the range of 0.1 μM-1 mM, and the recoveries in spiked blood samples were in the range of 70.7 %-104.6 % and 74.8 %-113.9 %, respectively. The precision and accuracy of the E-AB sensor for measuring Ima-Mes concentration in blood was similar to the standard LC-MS method. These results demonstrate that the developed E-AB sensor is an effective tool for rapid monitoring of Ima and Ima-Mes in blood.

ROSHAMBO: Open-Source Molecular Alignment and 3D Similarity Scoring.

Efficient virtual screening techniques are critical in drug discovery for identifying potential drug candidates. We present an open-source package for molecular alignment and 3D similarity calculations optimized for large-scale virtual screening of small molecules. This work parallels widely used proprietary tools and offers an approach complementary to structure-based virtual screening. Our package employs the PAPER software for optimizing molecular alignments based on Gaussian volume overlaps. GPU acceleration is utilized to significantly reduce computational time and resource requirements. After obtaining the optimal alignments between the target and the query molecules, both shape and color (based on pharmacophore features) scores are computed to assess molecular similarity, with aligned molecules optionally being output in sdf format. The package was benchmarked using the DUDE-Z public data sets. Results demonstrated the package's near-state-of-the-art performance and robustness across multiple target classes, with speed that enables many routine ligand-based drug discovery workflows. As an open-source and freely available resource (github.com/molecularinformatics/roshambo) with both a convenient Python API and command line interface, our package also addresses the need for accessible and efficient virtual screening tools in drug discovery.

Enhanced reliability of Cu-Sn bonding through the microstructure evolution of nanotwinned copper

Kirkendall voids are detrimental to the Cu-Sn bonding interface, causing the failure of the high-density package. Herein, the perpendicularly aligned nanotwinned Cu (p-ntCu) and the horizontally aligned nanotwinned Cu (h-ntCu) are prepared by controlling the electrodeposition procedure. The p-ntCu shows advantages both in fast-bonding process and in void suppression through the in-situ microstructure evolution. Compared with h-ntCu, the abundant perpendicularly aligned twin boundaries in p-ntCu provide fast interdiffusion paths to build a bonding interface. In the bonding process, p-ntCu grows to ultra-large-grained Cu with an average grain size of 6.68 μm. The reduced density of normal grain boundaries in p-ntCu lowers the Cu diffusion rate and contributes to more balanced interdiffusion at the bonding interface, which is confirmed by molecular dynamics simulation and kinetic calculations of intermetallic compound (IMC) growth. In addition, the low impurity content in p-ntCu further reduces the diffusion flux imbalance and limits the nucleation of Kirkendall vacancies. Consequently, the p-ntCu/Sn interface keeps void-free during 150 °C long-term thermal aging due to the synergistic effect of reduced grain-boundary diffusion and lower impurity content, which will be beneficial for achieving high-reliability Cu-Sn bonding.

Interaction of graphene oxide with tannic acid: computational modeling and toxicity mitigation in C. elegans.

Graphene oxide (GO) undergoes multiple transformations when introduced to biological and environmental media. GO surface favors the adsorption of biomolecules through different types of interaction mechanisms, modulating the biological effects of the material. In this study, we investigated the interaction of GO with tannic acid (TA) and its consequences for GO toxicity. We focused on understanding how TA interacts with GO, its impact on the material surface chemistry, colloidal stability, as well as, toxicity and biodistribution using the Caenorhabditis elegans model. Employing computational modeling, including reactive classical molecular dynamics and ab initio calculations, we reveal that TA preferentially binds to the most reactive sites on GO surfaces via the oxygen-containing groups or the carbon matrix; van der Waals interaction forces dominate the binding energy. TA exhibits a dose-dependent mitigating effect on the toxicity of GO, which can be attributed not only to the surface interactions between the molecule and the material but also to the inherent biological properties of TA in C. elegans. Our findings contribute to a deeper understanding of GO's environmental behavior and toxicity and highlight the potential of tannic acid for the synthesis and surface functionalization of graphene-based nanomaterials, offering insights into safer nanotechnology development.

Scalar and vectorized implementations of the density functional theory via Geant4 and GeantV project

In this paper, we present the implementation of the Density Functional Theory (DFT) method using the Geant4-DNA framework in the Single Instruction Single Data (SISD) mode. Furthermore, this implementation is improved in terms of execution time within the GeantV project with vectorization techniques such as Single Instruction Multiple Data (SIMD). Within this framework, a set of SIMD strategies in molecular calculation algorithms such as one-electron operators, two-electron operator, quadrature grids, and functionals, was implemented using the VecCore library. The applications developed in this work implement two DFT functionals, the Local Density Approximation (LDA) and the General Gradient Approximation (GGA), to approximate the molecular ground-state energies of small molecules and amino acids. To assess the performance of the implementations, a standard test simulation was performed in multiple CPU platforms. The SIMD vectorization strategy significantly accelerates DFT calculations, leading to time ratios ranging from 1.6 to 5.4 in either individual steps or entire implementations when compared with the scalar process within Geant4.

Pharmacoinformatics, Molecular Dynamics Simulation, and Quantum Mechanics Calculation Based Phytochemical Screening of Croton bonplandianum Against Breast Cancer by Targeting Estrogen Receptor-α (ERα)

Breast cancer progression is strongly influenced by estrogen receptor-α (ERα), a ligand-activated transcription factor that regulates hormone binding, DNA interaction, and transcriptional activation. ERα plays a key role in promoting cell proliferation in breast tissue, and its overexpression is associated with the advancement of breast cancer through estrogen-mediated signaling pathways. Targeting ERα is, therefore, a promising therapeutic strategy for breast cancer. However, there are currently no phytochemical-based drug candidates approved for effectively inhibiting breast cancer progression driven by elevated ERα expression. This study aims to identify phytochemical inhibitors from Croton bonplandianum against ERα using pharmacoinformatics approaches. Eighty-three bioactive compounds from C. bonplandianum were retrieved from the IMPPAT (Indian Medicinal Plants, Phytochemistry, and Therapeutics) database and screened through molecular docking for their binding affinity to ERα. The top candidates were further evaluated through molecular dynamics simulations, ADME analysis, toxicity assessment, and quantum mechanics-based DFT calculations. The thermodynamic properties and HOMO-LUMO energy gap values indicated that the selected compounds were both stable and active. Among them, 2,3-oxidosqualene (CID-5366020) and 5,8,11-eicosatriynoic acid, trimethylsilyl ester (CID-91696396) demonstrated the most potent inhibitory activity against ERα. These findings suggest that these compounds have significant potential as therapeutic agents for breast cancer treatment by targeting ERα.

Molecular and energetic analysis of the interaction and specificity of Maximin 3 with lipid membranes: In vitro and in silico assessments.

In this study, the interaction of antimicrobial peptide Maximin 3 (Max3) with three different lipid bilayer models was investigated to gain insight into its mechanism of action and membrane specificity. Bilayer perturbation assays using liposome calcein leakage dose-response curves revealed that Max3 is a selective membrane-active peptide. Dynamic light scattering recordings suggest that the peptide incorporates into the liposomal structure without producing a detergent effect. Langmuir monolayer compression assays confirmed the membrane inserting capacity of the peptide. Attenuated total reflection-Fourier transform infrared spectroscopy showed that the fingerprint signals of lipid phospholipid hydrophilic head groups and hydrophobic acyl chains are altered due to Max3-membrane interaction. On the other hand, all-atom molecular dynamics simulations (MDS) of the initial interaction with the membrane surface corroborated peptide-membrane selectivity. Peptide transmembrane MDS shed light on how the peptide differentially modifies lipid bilayer properties. Molecular mechanics Poisson-Boltzmann surface area calculations revealed a specific electrostatic interaction fingerprint of the peptide for each membrane model with which they were tested. The data generated from the in silico approach could account for some of the differences observed experimentally in the activity and selectivity of Max3.