CONTEXT: By utilizing first-principles calculations, we studied the electronic properties of graphdiyne nanosheet (GDY) and its Si-doped counterpart, Si-GDY. Both GDY and Si-GDY sheet surfaces were examined for the drug cisplatin (CP) adsorption using adsorption energy, charge transfer, and changes in electrical conductivity as indicators. Pure GDY has little affinity for CP, according to this study. Only 7.83% of the GDY surface's bandwidth energy changed after CP adsorption. CP on Si-GDY has a gaseous energy value of -18.75 kcal/mol and an aqueous energy value of - 49.39 kcal/mol. METHODS: The prescribed medications' water-phase solubility is determined by their solvation energy value. These charges are transferred between CP and the Si-GDY sheet, which is extremely positively charged, and this gives CP the necessary binding energy. After CP adsorption, electrical conductivity of Si-GDY increased by approximately 19.01%.

CONTEXT: PARP-1 plays an important role in DNA repair and apoptosis, and PARP-1 inhibitors have shown to be effective in the treatment of several malignancies. To evaluate the function of new PARP-1 inhibitors as anticancer adjuvant medicines, 3D-QSAR, molecular docking, and molecular dynamics (MD) simulations of a sequence of dihydrodiazepinoindolone derivatives PARP-1 inhibitors were undertaken in this study. METHODS: In this paper, 43 PARP-1 inhibitors were studied in a three-dimensional quantitative structure-activity relationship (3D-QSAR) using comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). CoMFA with q2 of 0.675 and r2 of 0.981 was achieved, as was CoMSIA with q2 of 0.755 and r2 of 0.992. The changed areas of these compounds are shown by steric, electrostatic, hydrophobic, and hydrogen-bonded acceptor field contour maps. Subsequently, molecular docking, and molecular dynamics simulations further confirmed that key residues Gly863 and Ser904 of PARP-1 are vital residues for protein interactions and their binding affinity. The effects of 3D-QSAR, molecular docking and molecular dynamics simulations supply a new route for the search of new PARP-1 inhibitors. Finally, we designed eight new compounds with exact activity and ADME/T properties.

CONTEXT: The unavailability of target-specific antiviral drugs for SARS-CoV-2 viral infection kindled the motivation to virtually design derivatives of 6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide as potential antiviral inhibitors against the concerned virus. The molecular docking and molecular dynamic results revealed that the reported derivatives have a potential to act as antiviral drug against SARS-CoV-2. The reported hit compounds can be considered for in vitro and in vivo analyses. METHODS: Fragment-based drug designing was used to model the derivatives. Furthermore, DFT simulations were carried out using B3LYP/6-311G** basis set. Docking simulations were performed by using a combination of empirical free energy force field with a Lamarckian genetic algorithm under AutoDock 4.2. By the application of AMBER14 force field and SPCE water model, molecular dynamic simulations and MM-PBSA were calculated for 100 ns.

CONTEXT: In recent years, fluorescent probe technology has received more and more attention. However, the photophysical and photochemical properties of probe molecules still need to be further explored. This paper presents the excited state intramolecular proton transfer (ESIPT) processes and photophysical properties of the probe molecule 4-bromo-2-((E)-((Z)-((5-bromo-1H-indol-2-yl) methylene) hydrazono) methyl) phenol (BHPL) and its four derivatives (BHPL2, BHPL3, BHPL4, and BHPL5). Infrared spectra and geometric structure analyses revealed that introducing the -NH2 group on the benzene ring with the hydroxyl group will enhance the intramolecular hydrogen bond, which benefits the ESIPT process. Combining their absorption and fluorescence spectra, it can be concluded that BHPL2 and BHPL4 are both excellent probe candidates due to their large Stokes shift. The hole and electron and root mean square displacement analyses manifest that the fluorescence quenching of BHPL4 may be due to the intramolecular charge transfer process. Potential energy curves of BHPL and its four derivatives noted that ESIPT process of the BHPL2 is the most favorable to occur. The frontier molecular orbital and NBO analyses indicated that besides introducing electron-donating groups to reduce the energy gap and enhance fluorescence emission, introducing double electron-withdrawing groups can also achieve this effect, explaining why the energy barrier of ESIPT process for BHPL2 is lower than BHPL5. This work would provide the theoretical basis for designing novel fluorescence probes with more prominent properties. METHODS: The ground (S0) and excited (S1) state structures of all compounds were optimized by density functional theory (DFT) and time-dependent (TDDFT) method, with B3LYP/6-311+G(d,p) level, respectively. The infrared spectra and potential energy curves were simulated at the same theoretical level. The reduced density gradient scatter plots and interaction region indicator isosurfaces were drawn using Multiwfn and VMD programs. The absorption and fluorescence spectra were simulated by the TDDFT/B3PW91/6-311+G(d,p) method. All the calculations in this work are carried out in Gaussian 16 program package.

CONTEXT: As a member of a large family of proteins that together regulate various aspects of cell growth and development, the epidermal growth factor receptor (EGFR) is a validated target for the development of new drugs. Herein, we compiled a library of 62 compounds from the PubChem database with similar pharmacophores as osimertinib, which to our knowledge represents the only drug capable of overcoming EGFR-T790M-mutated NSCLC until date. Subsequently, we launched a docking-based virtual screening campaign against the EGFR kinase with the compiled chemical entities. The virtual screen identified 3 hit candidates (CID_126667097, CID_137660592, and CID_137659061) with lower binding energy/higher affinity (- 8.7 kcal/mol, - 8.6 kcal/mol, and - 8.5 kcal/mol, respectively) than the standard osimertinib (- 8.4 kcal/mol). Molecular dynamics metrics such as RMSD, RMSF, ROG, and intermolecular H-bond were used to substantiate the stability of the promising drug candidates at the binding pocket of EGFR after 100,000 ps production run. Overall, our molecular modeling study portrayed CID_126667097, CID_137660592, and CID_137659061 as lead-like drug candidates that may be further developed for the treatment of EGFR-associated cancer disease. METHODS: Molecular docking was conducted with Autodock Vina. A total of 62 compounds were compiled for the docking screen, which were then downloaded in SMILE format and converted to Protein Data Bank (PDB) format using the Openbabel online server. Finally, Gromacs 2022.3 was used to perform MD simulation to substantiate the stability of the hit candidates.

Cellulose, hemicellulose, and lignin are the major chemical components in wood paper. Various types of wet and dry strength additives are used to enhance the optical and mechanical properties of recycled paper. One of the possible materials is the carbon nanotube. In order to explore the probability of the use of carbon nanotubes as reinforcing materials and to understand how carbon nanotubes affect the mechanical properties of paper, a single-walled carbon nanotube is inserted into a [Formula: see text] cellulose nanocrystal, and its mechanical properties are studied by using energy minimization and molecular dynamics (MD) simulations. During simulations, the crystals are stretched in the axial direction at a constant speed, and stress and strain are computed and recorded at the atomic level. Our results indicate that carbon nanotube can significantly enhance the mechanical properties of paper.

CONTEXT: Curcumin is a popular food additive around the world whose medicinal properties have been known since ancient times. The literature has recently highlighted several biological properties, but besides the health-related usages, its natural yellowish color may also be helpful for light-harvesting applications. This research aims to close a knowledge gap regarding the photophysical description of curcumin and its metallic complexes. METHODS: We conducted benchmark experiments comparing NEVPT calculations with several DFT functionals (B3LYP, M06-L, M06-2X, CAM-B3LYP, and ωB97X-D) for describing the UV spectra of curcumin and its metallo-derivative, curcumin-copper(II). Once we determined the most suitable functional, we performed tests with different basis sets and conditions, such as solvation and redox state, to identify their impact on excited state properties. These results are also reported for the curcumin-zinc(II) derivative. We found that the accuracy of DFT functionals depends strongly on the nature of curcumin's excitations. Intra-ligand transitions dominate the absorption spectra of the complexes. Curcumin absorption is marginally affected by solvation and chelation, but when combined with redox processes, they may result in significant modifications. This is because copper cation changes its coordination geometry in response to redox conditions, changing the spectrum. We found that, compared to a NEVPT reference, B3LYP is the best functional for a general description of the compounds, despite not being appropriate for charge transfer transitions. M06-L was the best for LMCT transitions. However, compared with NEVPT2 and PNO-LCCSD(T)-F12 results, no functional achieved acceptable accuracy for MLCT transitions.

Chagas disease (CD) is a tropical disease caused by the parasite Trypanosoma cruzi, transmitted by the barber insect. Currently, there are approximately 7 million infected people in the world, and it is estimated that 70 million people could contract this disease. The anacardic acid (AA) showed effectiveness in in silico and in vitro tests. The antichagasic potential of five sulfonamide molecules, derived from anacardic acid, was evaluated from a molecular approach based on the density functional theory (DFT), molecular dynamics (MD), and molecular docking (docking) calculations. Methyl 2-methoxy-6- (8- (methylsulfonamide) octyl) benzoate (SA1); 2-methoxy-6- (8- (phenylsulfonamide) octyl) benzoate (SA2); methyl 2-methoxy-6- (8- (2methylphenyl sulfonamide) octyl) benzoate (SA3); methyl 2-methoxy-6- (8-(methylphenylsulfonamide)octyl)benzoate (SA4); methyl2-(8-(2,5-dimethylphenylsulfonamide)octyl)-6-methoxybenzoate (SA5) were the investigated molecules. The DFT calculations were performed using the B3LYP/6-311+G (d, p) level of theory. The global and local reactivity data showed that SA1 shows the highest molecular reactivity, while SA2 is the most stable derivative. In addition, the structures of investigated molecules were confirmed by the linear correlations higher than 0.98 displayed between the experimental and calculated spectroscopic data (IR and NMR). Molecular docking of the molecules showed a greater prominence for the SA1, SA2, and SA4 molecules in the results of distances of ligand-cruzain. In molecular dynamics, SA2 obtained better stability due to greater interactions with important amino acids of cruzain.

CONTEXT: The inhibitory effect of asparagine (Asn) and its derivatives on iron (Fe) corrosion was studied by performing density functional theory (DFT) calculations. In this paper, the global and local reactivity descriptors of Asn in the protonated and neutral forms were evaluated. Also, the changes in reactivity were investigated when dipeptides were combined with Asn. Due to the increase in the reaction centers within their molecular structure, there was an enhancement in the inhibitory effect of these dipeptides. Moreover, the adsorption energies (Eads) and the adsorption configurations of Asn and small peptides (SPs) with most stability were determined on the surface of Fe(111). It was found that dipeptides had a chemical adsorption on these substrates. In the protonated forms, there was an enhancement in the absolute values of Eads between the inhibitors and the Fe(111) surfaces. Peptides were more likely to be adsorbed on the Fe surfaces, showing the great inhibitory effect of these moieties. The results of the current research demonstrate the possibility of utilizing SPs as efficient "green" corrosion inhibitors. METHODS: DFT computations were undertaken by employing the BIOVIA Material Studio with B3LYP-D3 functional and 6-31 + G* basis set. The theoretical evaluation of the inhibitory effect of asparagine (Asn) dipeptides, and the potential analysis of small peptides to protect against the corrosion of Fe, was done.

CONTEXT: The persistent spread of highly contagious COVID-19 disease is one of the deadliest occurrences in the history of mankind. Despite the distribution of numerous efficacious vaccines and their extensive usage, the perpetual effectiveness of immunization is being catechized. Therefore, discovering an alternative therapy to control and prevent COVID-19 infections has become a top priority. The main protease (Mpro) plays a key role in viral replication, making it an intriguing pharmacological target for SARS-CoV-2. METHODS: In this context, virtual screening of thirteen bioactive polyphenols and terpenoids of Rosmarinus officinalis L. was performed using several computational modules including molecular docking, ADMET, drug-likeness characteristics, and molecular dynamic simulation to predict the potential inhibitors against SARS-CoV-2 Mpro (PDB: 6LU7). The results suggest that apigenin, betulinic acid, luteolin, carnosol, and rosmarinic acid may emerge as potential inhibitors of SARS-CoV-2 with acceptable drug-likeness, pharmacokinetics, ADMET characteristics, and binding interactions comparable with remdesivir and favipiravir. These findings imply that some of the active components of Rosmarinus officinalis L. can serve as an effective antiviral source for the development of therapeutics for SARS-CoV-2 infection.

CONTEXT AND RESULTS: As an inorganic halide perovskite material, AgCaCl3, characterized by its high stability and environmental friendliness, is considered a potential candidate for major applications in optoelectronics and lens manufacturing. This work aimed to determine the electronic properties such as density of state (DOS) and band structure (BS) of AgCaCl3. The results showed that the material has an indirect band gap almost invariably at 1.5 eV in the pressure range studied. The dielectric function [Formula: see text], absorption coefficient [Formula: see text], optical conductivity [Formula: see text], reflectivity [Formula: see text], and the refractive index [Formula: see text] showed clearly that the perovskite AgCaCl3 preserved its optical characteristics within the chosen pressure range investigated. The calculated elastic constants C11, C12, and C14 as dynamic stability criteria for the elastic moduli such as bulk modulus (B), shear modulus (G), Young's modulus (Y), Poisson's ratio ([Formula: see text]), and anisotropy factor (A) showed that the material is a ductile plastic. Debye temperature ([Formula: see text]), isobaric and isochoric heat capacities (CP, CV), coefficient of the thermal expansion (α), Gibbs free energy (G), and entropy (S) were also studied. The results obtained provide a theoretical basis for experimental work and offer the possibility of future industrial applications of AgCaCl3. COMPUTATIONAL AND THEORETICAL TECHNIQUES: Density functional theory (DFT) calculations as implemented in the Wien2K code were used to study the mechanical and thermal properties of AgCaCl3 perovskite over a pressure range. Lattice parameters, electronic, and optical properties are optimized with the approximation of the generalized gradient of the Perdew-Burke-Ernzerhof function (PBE-GGA) function. The mechanical and thermodynamic properties were calculated using ElaStic and Gibbs2 codes, and the properties of AgCaCl3 over the pressure range investigated were predicted.

CONTEXT: Tetrylenoids, R2EXM (E = Si, Ge, and Sn; X = electronegative group; M = alkali metal), have electrophilic and nucleophilic properties just like carbenoid. As the products of carbenoid compounds with olefins, the cyclopropane fraction has been found to be biologically active in many natural and artificial compounds. Can carbenoid analogues of stannylenoid facilitate similar cyclopropanation reactions? METHODS: Addition reaction of the stannylenoid compound H2SnLiF with ethylene was investigated using density function theory (DFT) at the M062X/def2-TZVP level. The single-point energy calculations were performed on the basis of QCISD/def2-TZVP level. RESULTS: Two possible pathways were found for the addition reaction of H2SnLiF (R1) with ethylene (R2). The most favorable path is the two successive reactions of H2SnLiF and ethylene through the ternary ring product c-H2Sn(CH2)2 (P1) and then the formation of the five-membered ring product (P2). Solvation-related studies have shown that addition reactions are more likely to occur in the presence of THF solvents. This work provides theoretical support for the reactions of stannylenoid with olefins.

CONTEXT: Breast cancer is the most prevalent type of malignancies among women worldwide and is associated with serious physical and mental consequences. Current chemotherapies may lack successful outcomes; thus, the development of targeted recombinant immunotoxins is plausible. The predicted B cell and T cell epitopes of arazyme of the fusion protein are able to elicit immune response. The results of codon adaptation tool of herceptin-arazyme have improved from 0.4 to 1. The in silico immune simulation results showed significant response for immune cells. In conclusion, our findings show that the known multi-epitope fusion protein may activate humoral and cellular immune responses and maybe a possible candidate for breast cancer treatment. METHODS: In this study, the selected monoclonal antibody constituting herceptin and the bacterial metalloprotease, arazyme, was used with different peptide linkers to design a novel fusion protein to predict different B cell and T cell epitopes by the means of the relevant databases. Modeler 10.1 and I-TASSER online server were used to predict and validate the 3D structure and then docked to HER2-receptor using HADDOCK2.4 web server. The molecular dynamics (MD) simulations of the arazyme-linker-herceptin-HER2 complex were performed by GROMACS 2019.6 software. The sequence of arazyme-herceptin was optimized for the expression in prokaryotic host using online servers and cloned into pET-28a plasmid. The recombinant pET28a was transferred into the Escherichia coli BL21DE3. Expression and binding affinity of arazyme-herceptin and arazyme to human breast cancer cell lines (SK-BR-3/HER2 + and MDA-MB-468/HER2 -) were validated by the SDS-PAGE and cell‑ELISA, respectively.

The most dangerous subtype of breast cancer, triple-negative breast cancer (TNBC), accounts for 25% of all breast cancer-related deaths and 15% of all breast cancer cases. TNBC is distinguished by the lack of immunohistochemical expression of HER2, progesterone receptors, or oestrogen receptors. Although it has been reported that upregulation of EGFR and VEGFR-2 is associated with TNBC progression, no proven effective targeted therapy exists at this time. We used structural bioinformatics methods, including density functional theory, molecular docking, molecular dynamic simulation, pharmacokinetic and drug-likeness models, to identify promising EGFR/VEGFR-2 inhibitors from N-(4-methoxyphenyl)-2-[4-(3-oxo-3-phenylprop-1-en-1-yl) phenoxy] acetamide and six of its modified derivatives in light of the lack of effective targets inhibitor Version 14 of Spartan software was used to analyse density functional theory. The Schrodinger software suite 2018's Maestro interface was used for the molecular docking analysis, and the admetSAR and swissADME servers were used for drug-likeness and absorption, distribution, metabolism, excretion, and toxicity. All of the compounds showed strong electronic characteristics. Additionally, all of the tested compounds met the ADMET and drug-likeness requirements without a single instance of Lipinski's rule of five violations. Additionally, the molecules' levels of affinity for the target proteins varied. The highest binding affinities were demonstrated by the MOLb-VEGFR-2 complex (- 9.925 kcal/mol) and the MOLg-EGFR complex (- 5.032 kcal/mol). The interaction of the molecules in the domain of the EGFR and VEGFR-2 receptors was also better understood through molecular dynamic simulation of the complex.

CONTEXT: Molecular modeling of carbon nanotubes and lanthanide double-decker phthalocyanines hybrids is challenging due to the presence of 4f-electrons. In this paper, we analyzed the trends in structural changes and electronic properties when a lanthanide (La, Gd, and Lu) bisphthalocyanine molecule is adsorbed on the surface of two single-walled carbon nanotubes (SWCNTs) models: armchair and zigzag. The density functional theory (DFT) computations showed that the height of bisphthalocyanines complexes (LnPc2) when adsorbed on a nanotube (LnPc2+SWCNT) is the structural feature which is most affected by the nanotube model. The formation energy of the LnPc2+SWCNT hybrid depends on the metal atom and the nanotube chirality. LaPc2 and LuPc2 bind stronger to the zigzag nanotube, while for GdPc2, bonding to the armchair nanotube is the stronger one. The HOMO-LUMO gap energy (Egap) shows a correlation between the nature of lanthanide and the nanotube chirality. In the case of adsorption on armchair nanotube, Egap tends to match the gap of isolated LnPc2, whereas for adsorption on the zigzag nanotube, it is closer to the value for the isolated nanotube model. The spin density is localized on the phthalocyanines ligands (plus on Gd in the case of GdPc2), when the bisphthalocyanine is adsorbed on the surface of the armchair nanotube. For bonding to zigzag nanotube (ZNT), it extends over both components, except for LaPc2+ZNT, where spin density is found on the nanotube only. METHOD: All DFT calculations were carried out using the DMol3 module of Material Studio 8.0 software package from Accelrys Inc. The computational technique chosen was the general gradient approximation functional PBE in combination with a long-range dispersion correction developed by Grimme (PBE-D2), the double numerical basis set DN, and the DFT semi-core pseudopotentials.

Biguanide derivatives exhibit a wide variety of therapeutic applications, including anti-cancer effects. Metformin is an effective anti-cancer agent against breast cancer, lung cancer, and prostate cancer. In the crystal structure (PDB ID: 5G5J), it was found that metformin is found in the active site of CYP3A4, and the associated anti-cancer effect was explored. Taking clues from this work, pharmacoinformatics research has been carried out on a series of known and virtual biguanide, guanylthiourea (GTU), and nitreone derivatives. This exercise led to the identification of more than 100 species that exhibit greater binding affinity toward CYP3A4 in comparison to that of metformin. Selected six molecules were subjected to molecular dynamics simulations, and the results are presented in this work.

CONTEXT: Since the outbreak of COVID-19 in 2019, the 2019-nCov coronavirus has appeared diverse mutational characteristics due to its own flexible conformation. One multiple-mutant strain (Omicron) with surprisingly infective activity outburst, and affected the biological activities of current drugs and vaccines, making the epidemic significantly difficult to prevent and control, and seriously threaten health around the world. Importunately exploration of mutant characteristics for novel coronavirus Omicron can supply strong theoretical guidance for learning binding mechanism of mutant viruses. What's more, full acknowledgement of key mutated-residues on Omicron strain can provide new methodology of the novel pathogenic mechanism to human ACE2 receptor, as well as the subsequent vaccine development. METHODS: In this research, 3D structures of 32 single-point mutations of 2019-nCov were firstly constructed, and 32-sites multiple-mutant Omicron were finally obtained based one the wild-type virus by homology modeling method. One total number of 33 2019-nCov/ACE2 complex systems were acquired by protein-protein docking, and optimized by using preliminary molecular dynamic simulations. Binding free energies between each 2019-nCov mutation system and human ACE2 receptor were calculated, and corresponding binding patterns especially the regions adjacent to mutation site were analyzed. The results indicated that one total number of 6 mutated sites on the Omicron strain played crucial role in improving binding capacities from 2019-nCov to ACE2 protein. Subsequently, we performed long-term molecular dynamic simulations and protein-protein binding energy analysis for the selected 6 mutations. 3 infected individuals, the mutants T478K, Q493R and G496S with lower binding energies -66.36, -67.98 and -67.09 kcal/mol also presents the high infectivity. These findings indicated that the 3 mutations T478K, Q493R and G496S play the crucial roles in enhancing binding affinity of Omicron to human ACE2 protein. All these results illuminate important theoretical guidance for future virus detection of the Omicron epidemic, drug research and vaccine development.

CONTEXT: For the advancement in fields of organic and perovskite solar cells, various techniques of structural alterations are being employed on previously reported chromophores. This way, molecules with all the properties desired for better performance of solar cells can be achieved. In this regard, theoretical modeling of chromophores has gained quite an interest due to its ability to save time, resources, and money. Herein, five new Y-shaped donor materials were theoretically engineered by adding electron-withdrawing acceptors on reported 2DP molecule. The results explored that, in comparison to 2DP, the produced molecules showed red shift in the absorption peaks, smaller bandgaps and binding energies, lower excitation potential, and greater dipole moment and were also highly reactive. When paired with PC61BM, proposed compounds exhibited higher estimated power conversion efficiencies and open-circuit voltage in contrast to 2DP. Individually, 2DP1 possessed the largest conductivity of electrons and the maximum mobility of holes, due to its computed lowest reorganization energies. The results illustrate the viability of the proposed procedure, opening doors for the manufacturing of required solar cells with enhanced photovoltaic properties. METHODS: Precisely, a DFT and TD-DFT analysis on 2DP and all of the proposed molecules was conducted, using the functional MPW1PW91 at 6-31G (d,p) basis set to examine their optoelectronic aspects; additionally, the solvent state computations were studied with a TD-SCF simulation. For all these simulations, Gaussian 09 and GaussView 5.0 were employed. Moreover, the Origin 6.0 software, Multiwfn 3.8 software, and PyMOlyze 1.1 software were utilized for the visual depiction of the graphs of absorption, TDM, and DOS, respectively, of the studied molecules. A number of crucial aspects such as FMOs, bandgaps, light-harvesting efficiency, electrostatic potential, dipole moment, ionization potential, open-circuit voltage, fill factor, binding energy, interaction coefficient, chemical hardness-softness, and electrophilicity index were also investigated for the studied molecules.

The PI3K/Akt/mTOR pathway is one of the important pathways in many cancers. Akt is a serine-threonine kinase protein identified as a drug target for cancer treatment. Therefore, anticancer drugs are essential therapeutic targets for this pathway. In the current study, the inhibitory effect of two anticancer molecules, XFE and mitoxantrone, on AKT1 protein that can impact the activity of the AKT1 protein was investigated by using molecular docking and molecular dynamics (MD) simulations. The molecular docking results presented a relatively higher binding affinity of the mitoxantrone molecule in interaction with AKT1 than the XFE molecule. These results were validated by the MM/PBSA technique that was performed on obtained trajectories of 25 ns MD simulations. The mitoxantrone molecule has an intense binding energy of - 880.536 kcal/mol with AKT1 protein, while the XFE molecule shows a binding energy value of - 83.569 kcal/mol. Our findings from molecular dynamics simulations indicated that both molecules have favorite interactions with AKT1 protein. Other analyses, such as RMSF and hydrogen binding on trajectories obtained from MD simulations, indicated that the mitoxantrone molecule could be a relatively potent inhibitor for AKT1. Based on the results of this study and the structure of mitoxantrone, it is expected to be a good candidate for cancer treatment as a (PI3K)/Akt/mTOR inhibitor.

CONTEXT: Hydrogen bonds play a vital role in the stability and functioning of biomolecules. Suitable binary liquids are often used as prototypes for the study of biologically significant hydrogen bond studies and their intricate networks. Often, such systems show deviations in their physico-chemical properties from ideal conditions. As a continuation of our research interest in biologically important hydrogen-bonded systems, this paper reports the classical molecular dynamic studies on mixtures of aniline with 8 primary alcohols (CRH2R+1-OH, R = 1 to 8) for the complete concentration range. The energetics results indicate the predominance of OH--O interactions over other hydrogen bonds. Structures in the network are analyzed using radial distribution function (RDF), hydrogen bond statistics, and graph theoretical analysis (GTA). Coordination numbers, hydrogen bond statistics, and GTA show a bunching of alcohol-alcohol hydrogen bonds for lower aniline concentrations, while the aniline-aniline interactions are not affected by changes in the concentration. METHODS: Interaction energies are calculated using B3LYP/6-311G++(d, p) density functional theory using Gaussian-09. The molecular dynamics simulations are carried out using GROMACS (V 2020.6) with the OPLS/AA force field and the simulation box is visualized using VMD. The NetworkX Python package is used for GTA calculation.

CONTEXT: In this paper, the adsorption characteristics of five sulfonamide antibiotic molecules on carbon nanotubes were investigated using density functional theory (DFT) calculations. The adsorption configurations of different adsorption sites were optimized, and the most stable adsorption configuration of each sulfonamide molecule was determined by adsorption energy comparison, and the relative adsorption stability of five sulfonamide molecules on carbon nanotubes was determined by comparing their adsorption energies, i.e., sulfamethazine > sulfadiazine > sulfamerazine > sulfamethoxazole > sulfanilamide. The electron densities of the adsorption configurations were then calculated to confirm that the adsorption of five sulfonamide drug molecules on carbon nanotubes should be physical adsorption. Moreover, the adsorption energy of five sulfonamide molecules on carbon nanotubes in the aqueous environment was larger than that in the vacuum even though the adsorption process remain to be physical adsorption. The adsorption characteristics of the five sulfonamide molecules in various acid-base environments were finally investigated. In contrast, the adsorption energies of the five drug molecules in acid-base environments were significantly reduced, indicating that carbon nanotubes may need to have a suitable pH range to achieve the optimal adsorption effect when they are used for the treatment of sulfonamide antibiotics. METHODS: In this paper, we use density functional theory (DFT) with PBE functional to study the adsorption properties of five sulfonamides on carbon nanotubes. The structural optimization and the calculation of electronic structural properties are carried out by CP2K package (version 7.1), adopting the DZVP-MOLOPT-SR-GTH basis set and Goedeck-Teter-Hutter (GTH) pseudo potential. Grimme's D3 correction is used to during all the calculations to correctly capture the influence of the van der Waals interactions.

CONTEXT: Nanosensors and actuators are frequently made of graphene. Any defect in the graphene's manufacturing has an impact on its sensing performance and on its dynamic behaviour. Using a molecular dynamics technique, the influence of pinhole defects and atomic defects on the performance parameters of single-layer graphene sheets (SLGSs) and double-layer graphene sheets (DLGSs) with various boundary conditions and lengths is explored. In contrast to the perfect nanostructure of a graphene sheet, defects are described as holes formed by atomic vacancies. As the number of defects increases, the simulation results show that the presence of defects has the greatest impact on the resonance frequency of SLGSs and DLGSs. The influence of pinhole defect (PD) and atomic vacancy defect (AVD) on armchair, zigzag, and chiral SLGSs and DLGSs was investigated in this article using molecular dynamics simulation. The influence of both types of defects is largest when it is adjacent to the fixed support for all three different types of graphene sheets, i.e. armchair, zigzag, and chiral. METHODS: The structure of the graphene sheet has been created using ANSYS APDL software. In the structure of the graphene sheet, atomic and pinhole defects have been generated. SLG and DLG sheets are modelled using a space frame structure that is identical to a three-dimensional beam. Dynamic analysis of single-layer and double-layer graphene sheets performed with different lengths using the atomistic finite element method. The interlayer separation in the form of Van der Waals interaction is modelled using characteristic spring element (Combin14). The upper and lower sheets of DLGSs are described as elastic beams connected by a spring element. With atomic vacancy defect for the bridged boundary condition, the highest frequency of 2.86 × 108 Hz was found for zigzag DLG (20 0) and with same boundary condition for pinhole defect 2.79 × 108 Hz frequency achieved. In a single-layer graphene sheet with an atomic vacancy and cantilever boundary condition, the maximum efficiency was 4.13 × 103 Hz for SLG (20 0), while in a pinhole defect, it produced 2.73 × 107 Hz. Moreover, the elastic parameters of beam components are calculated using the mechanical properties of covalent bonds between carbon atoms in the hexagonal lattice. The model has been tested against previous research. The focus of this research is to develop a mechanism for determining how defects affect graphene frequency band in application as nano resonators.

Enhancing the thermoelectric performance in engineered graphene nanoribbons is used to produce thermoelectric nanodevices, which are important in many applications. By using a chemical doping method, armchair graphene nanoribbons (AGNRs) can have thermoelectric properties that are tunable. We predicted that changing the number and geometrical pattern of zinc oxide (ZnO) dimers in an AGNR can engineer thermoelectric properties, so we used density functional-based tight binding (DFTB) combined with the non-equilibrium Green's function (NEGF) to investigate the geometric, electronic, and thermoelectric properties of the AGNR with and without various dopants of ZnO dimers. With three forms of ZnO dimers, ortho, meta, and para dimers, different concentration ratios of Zn and O atoms are used. Our results indicate that the electronic features of AGNR are influenced not only by the concentrations of ZnO dimers but also by the geometrical pattern of ZnO dimers in the AGNR. These results are helpful in better understanding the effect of chemical doping on the transport properties of AGNRs and in motivating nanodevices to improve their thermoelectric performance.

CONTEXT: Nanomaterials enjoy a great surface-to-surface area ratio, small size, extremely high stability, satisfactory bio-compatibility, improved permeability, specificity in receptor targeting, and tunable lifetime. This paper investigates alkali metal-doped borospherenes M@C4B32 (in which M denotes K, Na, and Li) as a highly efficient alternative for the delivery of drugs using density functional theory (DFT) calculations. A borospherene with a B36 nanocage doped with four C atoms (i.e., C4B32) recently showed promising performance. Therefore, the present work investigates C4B32 nanoclusters doped with alkali metals for the effective delivery of drugs. METHODS: This paper primarily seeks to evaluate the interaction between thioguanine (TG) as a cancer drug and pristine M@C4B32 through DFT (PBE/6-31 + G (d)) calculations. The UV-Vis spectroscopy indicated a redshift in the complex electronic spectra to higher wavelengths (i.e., lower energy levels). Hence, K@C4B32 was concluded to be effective in TG delivery.

CONTEXT: The Hedgehog (Hh) signaling pathway is a crucial regulator of various cellular processes. Dysregulated activation of the Smoothened (SMO) oncoprotein, a key component of the Hh pathway, has been implicated in several types of cancer. Although SMO inhibitors are important anti-cancer therapeutics, drug-resistant SMO mutants have emerged, limiting their efficacy. This study aimed to discover stable SMO inhibitors for both wild-type and mutant SMOs, using a 12-feature pharmacophore model validated for virtual screening. One lead compound, LCT10312, was identified with high affinity to SMO and showed a significant conformational change in the SMO structure upon binding. Molecular dynamic simulation revealed stable interaction of LCT10312 with SMO and large atom motions, indicating SMO structural fluctuation. The lead compound showed high predicted binding scores to several clinically relevant SMO mutants. METHODS: A ligand-based pharmacophore model was developed from 25 structurally clustered SMO inhibitors using LigandScout v3.12 software and virtually screened for hit identification from a library of 511,878 chemicals. Molecular docking was employed to identify potential leads based on SMO affinities. Molecular dynamic simulation (MDS) with GROMACS v5.1.4 was performed to analyze the structural changes of SMO oncoprotein upon binding lead compound(s) and cyclopamine as the control for 100 ns. The binding affinity of lead compound(s) was predicted on clinical and laboratory SMO mutants.

Diglycidyl ether bisphenol A (DGEBA) is a thermosetting polymer with excellent cross-linking properties and an irreversible network structure that forms polymer chains when chemically reacting with hardeners such as amines and anhydrides. The resulting compound has exceptional thermomechanical and structural properties. The properties of the final compound are heavily influenced by cross-linking and network structure. In the present research, molecular dynamics (MD) simulations were used to investigate the mechanical properties of chemically cross-linked DGEBA and the curing agent diethyl toluene diamine (DETDA). The MD simulation was used to perform the cross-linking, and a comprehensive study on the mechanical properties of DGEBA/DETDA was conducted. To investigate the mechanical properties, the developed model was reinforced with hexagonal boron nitride nanosheet (h-BNNS) at various weight percentages (wt.%). The results showed that the density of the neat DGEBA/DETDA increases with increasing cross-linking. It is 1.13 g/cm3 at 90% cross-linking. Almost all cross-linking densities of neat DGEBA/DETDA had higher mechanical properties. At room temperature (300 K), the elastic modulus increases from 2.58 to 2.98 GPa for cross-linking densities of 80% (EP80), 85% (EP85), and 90% (EP90). The elastic modulus of EP85 and EP90 is 3% lower and 9% higher than the experimental value (2.71 GPa), respectively. In almost all cross-linking densities, the elastic modulus of the h-BNNS reinforced DGEBA/DETDA increases with the weight percentage (wt%) of the h-BNNS. Shear and bulk modulus increase when h-BNNS is added to the DGEBA/DETDA matrix.

CONTEXT: In this study, the reactions of hydrated electron (e-(aq)) with alkyl and aryl halides were simulated with an ab initial molecular dynamics (AIMD) method to reveal the underlying mechanism. An original protocol was developed for preparing the proper initial wavefunction guess of AIMD, in which a single electron was curled in a tetrahedral cavity of four water molecules. Our results show that the stability of e-(aq) increases with the hydrogen bond grid integrity. The organic halides prefer to react with e-(aq) in neutral or alkaline environment, while they are more likely to react with hydrogen radical (the product of e-(aq) and proton) under acidic conditions. The reaction between fluorobenzene/fluoromethane and hydrogen radical is considered as the least favorable reaction due to the highest reaction barriers. The bond dissociation energy (BDE) suggested that the cleavage of the carbon-halogen bond of their anion radical might be a thermodynamically favorable reaction. AIMD results indicated that the LUMO or higher orbitals were the e-(aq) migration destination. The transplanted electron enhanced carbon-halogen bond vibration intensively, leading to bond cleavage. The solvation process of the departing halogen anions was observed in both fluorobenzene and fluoromethane AIMD simulation, indicating that it might have a significant effect on enthalpy. Side reactions and byproducts obtained during the AIMD simulation suggested the complexity of the e-(aq) reactions and further investigation was needed to fully understand the reaction mechanisms. This study provided theoretical insight into the pollutant environmental fate and constructed a methodological foundation for AIMD simulation of analogous free radical reactions. METHODS: The theoretical calculation was conducted on the combination of Gaussian16 and ORCA5.0.3 software packages. The initial geometries, as well as the wavefunction initial guesses, were obtained at PBE0/ma-def2-TZVP/IEFPCM-water level in Gaussian16 unless otherwise stated. AIMD simulations were performed at the same level in ORCA. Wavefunction analysis was carried out with Multiwfn. The details methods were described in the section "Computational details" section.

CONTEXT: In recent years, undivided attention has been given to the unique properties of layered nitrogenated holey graphene (C2N) monolayers (C2NMLs), which have widespread applications (e.g., in catalysis and metal-ion batteries). Nevertheless, the scarcity and impurity of C2NMLs in experiments and the ineffective technique of adsorbing a single atom on the surface of C2NMLs have significantly limited their investigation and thus their development. Within this research study, we proposed a novel model, i.e., atom pair adsorption, to inspect the potential use of a C2NML anode material for KIBs through first-principles (DFT) computations. The maximum theoretical capacity of K ions reached 2397 mA h g-1, which was greater in contrast with that of graphite. The results of Bader charge analysis and charge density difference revealed the creation of channels between K atoms and the C2NML for electron transport, which increased the interactions between them. The fast process of charge and discharge in the battery was due to the metallicity of the complex of C2NML/K ions and because the diffusion barrier of K ions on the C2NML was low. Moreover, the C2NML has the advantages of great cycling stability and low open-circuit voltage (approximately 0.423 V). The current work can provide useful insights into the design of energy storage materials with high efficiency. METHODS: In this research, we used B3LYP-D3 functional and 6-31 + G* basis with GAMESS program to calculate adsorption energy, open-circuit voltage, and maximum theoretical capacity of K ions on the C2NML.

CONTEXT: Leukaemia has become a serious threat to human health. Although tyrosine kinase inhibitors (TKIs) have been developed as targets for the remedy of leukaemia, drug resistance occurs. Research demonstrated that the simultaneous targeting of sphingosine kinase 1 (Sphk1) and Sirtuin 1 (Sirt1) can downregulate myeloid cell leukaemia-1 (MCL-1), overcome the resistance of tyrosine kinase inhibitors, and play a synergistic inhibitory impact on leukaemia treatment. METHODS: In this study, virtual screening of 7.06 million small molecules was done by sphingosine kinase 1 and Sirtuin 1 pharmacophore models using Schrödinger version 2019; after that, ADME and Toxicity molecule properties were predicted using Discovery Studio. Molecular docking using Schrödinger selected five molecules, which have the best binding affinity with sphingosine kinase 1 and Sirtuin 1. The five molecules and reference inhibitors were constructed with a total of 12 systems with GROMACS that carried out 100 ns molecular dynamics simulation and molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) calculation. Due to compound 3 has the lowest binding energy, its structure was modified. A series of compounds docked with sphingosine kinase 1 and Sirtuin 1, respectively. Among them, QST-LC03, QST-LD05, QST-LE03, and QST-LE04 have the better binding affinity than reference inhibitors. Moreover, the SwissADME and PASS platforms predict that 1, 3, QST-LC03, and QST-LE04 have further study value.

The adsorption of SO2, NO2, and NH3 toxic gases on Al24N24 and Al24N23C nanocages was investigated by using density functional theory (DFT) calculations. The adsorption energies, frontier orbitals, charge transfer using natural bonding orbital (NBO) analysis, dipole moment, the partial density of states (PDOS), thermodynamic relationships, non-covalent interaction (NCI), and quantum theory of atoms in molecules (QTAIM) were considered. The results reveal that carbon-doped Al24N24 nanocage increases the adsorption energies for SO2 and NO2 gases while decreasing the adsorption energy of NH3 gas. The ΔG for all configurations were negative except the configurations A1 and G2 confirming the weak adsorption of these two complexes. In conclusion, Al24N24 and Al24N23C nanocages are in general promising adsorbents for the removal of SO2, NO2, and NH3 toxic gases. The Al24N24 and Al24N23C nanocages are ideal electronic materials.

CONTEXT: In the replication of SARS-CoV-2, the main protease (Mpro/3CLpro) is significant. It is conserved in a number of novel coronavirus variations, and no known human proteases share its cleavage sites. Therefore, 3CLpro is an ideal target. In the report, we screened five potential inhibitors (1543, 2308, 3717, 5606, and 9000) of SARS-CoV-2 Mpro through a workflow. The calculation of MM-GBSA binding free energy showed that three of the five potential inhibitors (1543, 2308, 5606) had similar inhibitor effects to X77 against Mpro of SARS-CoV-2. In conclusion, the manuscript lays the groundwork for the design of Mpro inhibitors. METHODS: In the virtual screening phase, we used structure-based virtual screening (Qvina2.1) and ligand-based virtual screening (AncPhore). In the molecular dynamic simulation part, we used the Amber14SB + GAFF force field to perform molecular dynamic simulation of the complex for 100 ns (Gromacs2021.5) and performed MM-GBSA binding free energy calculation according to the simulation trajectory.

Molecular high-order harmonic generation and molecular orbital ionization probabilities are calculated under orthogonally and linearly polarized two-color laser fields. When a second-harmonic field is applied, the high-order harmonics generated under the linearly polarized two-color laser fields in the antiparallel case are stronger than those generated in the orthogonal polarization case and even stronger than those of the parallel polarization case. The results show that ionization probabilities of various orbitals and harmonic orders are dependent on spatial symmetry of molecular orbitals. It is found that the ionization of low-lying Kohn-Sham molecular orbitals contributes significantly to the ionization and molecular high-order harmonic generation processes. The ionization probability maximum occurs when molecular orbital densities are maximum in the direction of laser field polarization. Furthermore, we show that the degeneracy of π orbitals is broken when the laser-molecule alignment angle deviates from the field axis. Accordingly, we indicated one component of the π orbital is effectively contributed to the ionization and high-order harmonic generation processes. Finally, to confirm the recollision model in the high-order harmonic generation, the quantum time-frequency analysis is used to extract electron paths information on subcycle time scales.

CONTEXT: The morphologies of hexanitrohexaazaisowurtzitane (CL-20) and 1,4-dinitroimidazole (1,4-DNI) co-crystal under vacuum or solvent at different temperatures were predicted. The CL-20/1,4-DNI co-crystal has six important growth crystal planes: (002), (011), (101), (11‒1), (110), (111). The areas of (002), (101), and (011) planes account for a relatively large proportion, which are important crystal planes that affect the crystal morphology. The crystal habits at different temperatures were simulated. The simulation results showed that the crystal plane attachment energy of CL-20 and 1,4-DNI co-crystal increases with the increase of temperature, indicating that the increase of temperature is conducive to the growth of crystal planes. The aspect ratio decreases with the increase of temperature and the morphology of co-crystal becomes more spherical at a higher temperature. The theoretical predictions are in good agreement with the experiment. The simulation results can provide guidance for the crystallization of CL-20/1,4-DNI to obtain a nearly spherical crystal morphology. METHODS: The CL-20/1,4-DNI unit cell structure was geometrically optimized by the COMPASS force field. The AE model was used to predict the morphology of CL-20/1,4-DNI under vacuum, resulting in the most morphologically important growth planes. Ethyl acetate was selected as the solvent. The interaction energy between the solvent and the crystal plane, and the attachment energies in solvent at 298 K, 320 K, 340 K, 360 K, and 380 K were predicted. The NVT ensemble is used in the molecular dynamics calculation process. The simulation step is 1 fs and the total simulation time is 500 ps. The Andersen thermostat is selected as the temperature control method. In the potential energy calculation, the atom-based and Ewald methods were selected to calculate the van der Waals force and the electrostatic interaction force, respectively.

CONTEXT: At present, sulfonamides and their metal complexes have received a new impetus for development. Of particular interest is the study of molecular and crystal structures, which takes into account weak non-valent interactions. Despite the low energy of such interactions, in many cases, they act collectively, and the sum of their actions can play a significant role. As a result, the spectrum of medical and biological activity of new metal complexes is expanded. In this regard, the synthesis and study of the molecular and crystal structure of sulfonamides and their metal complexes is of undoubted relevance. In this work, we studied non-valent intra- and intermolecular interactions in ligands of sulfonamide-substituted imidazo[2,1-b]thiazoles and their previously unknown complexes with CuCl2. The performed analysis of the data obtained by X-ray diffraction analysis made it possible to establish the intramolecular π-stacking interaction in imidazothiazole ligands, which is retained in their complexes with CuCl2. Within the framework of QTAIM topological analysis of electron density and DORI analysis, stereoelectronic and topological structures were studied. In the complexes, tetral, chalcogen, and pnycogen new interligand non-valent interactions were established. The energies of all established types of non-valent interactions have been calculated, and their comparative evaluation has been made. METHODS: X-ray data of new arylsulfonylamino-substituted derivatives of imidazo[2,1-b]thiazoles and their metal complexes with CuCl2 have been studied. To determine the theoretical prerequisites for the occurrence of π-stacking in the molecules under study, the QTAIM method was used in the framework of the DFT/B3LYP/6-311 + G(d) calculation using the GAUSSIAN 09 program. In addition, the DORI electron density region overlap indicator and the Multiwfn program were used to analyze non-valent interactions.

Magnaporthe oryzae is the causal agent of rice blast, and understanding how abiotic stress affects the resistance of plants to this disease is useful for designing disease control strategies. In this paper, the effects of temperature and microwave irradiation on the effector complex comprising APikL2A from M. oryzae and sHMA25 from foxtail millet were investigated by molecular dynamics simulations using the GROMACS software package. While the structure of APikL2A/sHMA25 remained relatively stable in a temperature range of 290 K (16.85 °C) to 320 K (46.85 °C), the concave shape of the temperature-dependent binding free energy curve indicated that there was maximum binding affinity between APikL2A and sHMA25 at 300 K-310 K. This coincided with the optimum infectivity temperature, thus suggesting that coupling of the two polypeptides may play a role in the infection process. A strong oscillating electric field destroyed the structure of APikL2A/sHMA25, although it was stable and not susceptible to weak electric fields.

Discerning the determinants of protein thermostability is very important both from the theoretical and applied perspective. Different lines of evidence seem to indicate that a dynamical network of salt bridges/charged residues plays a fundamental role in the thermostability of enzymes. In this work, we applied measures of dynamic variance, like the Gini coefficients, Kullback-Leibler (KL) divergence and dynamic cross correlation (DCC) coefficients to compare the behavior of 3 pairs of homologous proteins from the thermophilic bacterium Thermus thermophilus and mesophilic Escherichia coli. Molecular dynamic (MD) simulations of these proteins were performed at 303 K and 363 K. In the characterization of their side chain rotamer distributions, the corresponding Gini coefficients and KL-divergence both revealed significant correlations with temperature. Similarly, a DCC analysis revealed a higher trend to de-correlate the movement of charged residues at higher temperatures in the thermophilic proteins, when compared with their mesophilic homologues. These results highlight the importance of dynamic electrostatic network interactions for the thermostability of enzymes.

CONTEXT: In this study, the electronic transport of (6, 3) two side-closed single-walled boron nitride nanotubes ((6, 3) TSC-SWBNNTs) located between two electrodes of (5, 5) conductive carbon nanotubes is investigated. Introducing carbon impurities instead of nitrogen and boron atoms in different locations of two side-closed (6, 3) SWBNNTs would change the transmission spectrum and reduce the gap. As the bias voltage increases, the peaks of the transmission spectrum become sharper and narrower. Substituting carbon impurities instead of nitrogen atoms leads to larger currents than substituting carbon impurities instead of boron. For the carbon impurity instead of N atoms, the current in the center is observed to be larger than currents on the left and right sides. In addition, negative resistance can be seen in current-voltage diagrams, which are used in the construction of high-speed electronic switches in electrical circuits. METHOD: Due to the larger number of atoms, the study of structures by the common approach is time-consuming and some times impossible. Hence, in this research, the Quantum ATK simulation software is used to investigate the characteristics of electronic transport. For this purpose, the Slater-Koster method and the tight-closure approximation are used. In this method, the non-equilibrium Green function (NEGF) approach is employed.