The discovery of antiviral approaches to prevent or cure respiratory syncytial virus (RSV) infections is critical, particularly because RSV is one of the most common causes of infant respiratory problems. There is currently no approved vaccination available to treat RSV infections. FDA has approved the drug ribavirin, but it is not sufficient to treat RSV. This work aimed to find and study in silico anti-RSV drugs that target matrix protein and nucleoprotein. In this study, we have identified five drug candidates that had better binding energies than ribavirin. Garenoxacin appeared as top lead compounds between them. AutoDock Vina was used to execute molecular docking of a library of chosen chemicals. The high-score compound was then confirmed using the Maestro 12.3 module's molecular dynamics simulation and the binding energies derived using Prime/Molecular Mechanics Generalized Born Surface Area (Prime/MM-GBSA). Comparative molecular dynamics simulations revealed that garenoxacin has better stability and high residue contacts with high binding affinity than ribavirin. This study showed garenoxacin could prevent RSV infection better than ribavirin. In pursuing a more effective RSV control drug, additional research into these chemicals in vitro and in vivo is essential.

Flavanone compounds are naturally occurring phytochemicals present in most of citrus fruits reported to be a potential anticancer moiety as it majorly participates in the inhibition of the cell cycle, apoptosis, and angiogenesis. Because of poor bioavailability, natural flavanones were not used as therapeutic targets so flavanone congeners were prepared by modifying at B-functional group using compound libraries such as PubChem Database. Cyclin-dependent kinase is primarily activating the cell cycle and potentiating the M phase, in order to control the cell cycle in cancer cyclin-dependent pathway was targeted and potential cyclin D/CDK4 receptor protein was retrieved from Protein Data Bank (PDBID:2W9Z). The binding site was determined using FlexX docking. Flavanone and its congeners were docked against the 2W9Z receptor protein with the docking software FlexX. For validation of docking results, molecular dynamics simulations of the best-fitting molecule were carried out using Desmond Package. Noncovalent interactions like hydrogen bonds, electrostatic interaction, and Van der walls potentials for stable conformations were calculated. Thus, upon docking and molecular dynamics studies, we discovered the potential flavanone derivatives such as Flavanone 20, Flavanone 25, and Flavanone 29, will become a potential drug target in controlling cell cycle arrest and may become a futuristic candidate in targeting cancer.

INTRODUCTION: Crimean-Congo haemorrhagic fever virus (CCHFV) has tripartite RNA genome and is endemic in various countries of Asia, Africa and Europe. METHOD: The present study is focused on mutation profiling of CCHFV L segment and phylogenetic clustering of protein dataset into six CCHFV genotypes. RESULTS: Phylogenetic tree rooted with NCBI reference sequence (YP_325663.1) indicated less divergence from genotype III and the sequences belonging to same genotypes have shown less divergence among each other. Mutation frequency at 729 mutated positions was calculated and 563, 49, 33, 46 and 38 amino acid positions were found to be mutated at mutation frequency intervals of 0-0.2, 0.21-0.4, 0.41-0.6, 0.61-0.8 and 0.81-1.0 respectively. Thirty-eight highly frequent mutations (0.81-1.0 interval) were found in all genotypes and mapping in L segment (encoded for RdRp) revealed four mutations (V2074I, I2134T/A, V2148A and Q2695H/R) in catalytic site domain and no mutation in OTU domain. Molecular dynamic simulation and in silico analysis showed that catalytic site domain displayed large deviation and fluctuation upon introduction of these point mutations. CONCLUSION: Overall study provides strong evidence that OTU domain is highly conserved and less prone to mutation whereas point mutations recorded in catalytic domain have affected the stability of protein and were found to be persistent in the large population.

CONTEXT: Comparatively, metal-free sensitizers featuring the chalcogen family receive less attention despite known electronic properties for metal-chalcogenide materials. This work reports an array of optoelectronic properties using quantum chemical methods. Observed red-shifted bands within the UV/Vis to NIR regions with absorption maxima > 500 nm were consistent with increasing chalcogenide size. There is a monotonic down-shift in the LUMO and ESOP energy consistent with O 2p, S 3p, Se 4p, to Te 5p atomic orbital energies. Excited-state lifetime and charge injection free energies follow the decreasing order of chalcogenide electronegativity. Adsorption energies of dyes on TiO2 anatase (101) range between - 0.08 and - 0.77 eV. Based on evaluated properties, selenium- and tellurium-based materials show potential use in DSSCs and futuristic device applications. Therefore, this work motivates continued investigation of the chalcogenide sensitizers and their application. METHODS: The geometry optimization was performed at B3LYP/6-31 + G(d,p) and B3LYP/LANL2DZ level of theory for lighter and heavier atoms, respectively, using Gaussian 09. The equilibrium geometries were confirmed by the absence of imaginary frequencies. Electronic spectra were obtained at CAM-B3LYP/6-31G + (d,p)/LANL2DZ level of theory. Adsorption energies for dyes on a 4 × 5 supercell TiO2 anatase (101) were obtained using VASP. The dye-TiO2 optimizations were employed using GGA and PBE with the PAW pseudo-potentials. The energy cutoff was set at 400 eV and convergence threshold for self-consistent iteration was set to 10-4, and van der Waals were accounted using DFT-D3 model and on-site Coulomb repulsion potential set at 8.5 eV for Ti.

CONTEXT: Lymphatic filariasis, generally called as elephantiasis, is a vector-borne infectious disease caused by the filarial nematodes, mainly Wuchereria bancrofti, Brugia malayi, and Brugia timori, which are transmitted through mosquitoes. The infection affects the normal flow of lymph leading to abnormal enlargement of body parts, severe pain, permanent disability, and social stigma. Due to the development of resistance as well as toxic effects, existing medicines for lymphatic filariasis are becoming ineffective in killing the adult worms. It is essential to search novel filaricidal drugs with new molecular targets. Asparaginyl-tRNA synthetase (PDB ID: 2XGT) belongs to the group of aminoacyl-tRNA synthetases that catalyze specific attachment of amino acids to their tRNA during protein biosynthesis. Plants and their extracts are well-known medicinal practice for the management of several parasitic infectious diseases including filarial infections. METHODS: In this study, asparaginyl-tRNA synthetase of Brugia malayi was used as a target to perform virtual screening of plant phytoconstituents of Vitex negundo from IMPPAT database, which exhibits anti-filarial and anti-helminthic properties. A total of sixty-eight compounds from Vitex negundo were docked against asparaginyl-tRNA synthetase using Autodock module of PyRx tool. Among the 68 compounds screened, 3 compounds, negundoside, myricetin, and nishindaside, exhibited a higher binding affinity compared to standard drugs. The pharmacokinetic and physicochemical prediction, stability of ligand-receptor complexes via molecular dynamics simulation, and density functionality theory were done further for the top-scored ligands with receptor.

The present computational study using B3LYP functional and 6-31+G(d) basis set has been accomplished to investigate the mechanism of the inverse demand Diels-Alder reaction between pyridyl imine and propene. The highly charged dicationic superelectrophilic diene with exceptionally low-lying LUMO makes the cycloaddition reaction with propene more favorable by significantly lowering the activation energy. The Wiberg bond indices are calculated in accordance with the formation and breaking processes of bonds. The synchronicity concept is also utilized to explain the global nature of the reaction. A potential outcome of this investigation is the utilization of propene as a C2 building block in the industry.

CONTEXT: In this work, a comprehensive study concerning the physical properties of ternary alloys system (AlP1-xBix) at different concentrations is presented. The obtained results from our first-principle calculations are compared with previously reported studies in the literature and discussed in detail. Our computed results are found in a nice agreement where available with earlier reported results. Electronic band structures at the above-mentioned concentrations are also determined. Likewise, the impact of the varying temperature and pressure on Debye temperature, heat capacity, and entropy is analyzed as well. Furthermore, elastic constants and related elastic moduli results are also computed. Our results show that alloys are stable and found to be in brittle nature. This is the first quantitative study related to ternary alloys (AlP1-xBix) at mentioned concentrations. We soon expect the experimental confirmation of our predictions. METHOD: The calculations are performed, at concentrations x=0.0, 0.25, 0.5, 0.75, and 1.0 by using the "full potential (FP) linearized (L) augmented plane wave plus local orbital (APW+lo) method framed within density functional theory (DFT)" as recognized in the "WIEN2k computational code". The "quasi-harmonic Debye model" approach is employed to determine the thermal properties of the title alloys.

CONTEXT: In recent decades, drug development has become extremely important as different new diseases have emerged. However, drug discovery is a long and complex process with a very low success rate, and methods are needed to improve the efficiency of the process and reduce the possibility of failure. Among them, drug design from scratch has become a promising approach. Molecules are generated from scratch, reducing the reliance on trial and error and prefabricated molecular repositories, but the optimization of its molecular properties is still a challenging multi-objective optimization problem. METHODS: In this study, two stack-augmented recurrent neural networks were used to compose a generative model for generating drug-like molecules, and then reinforcement learning was used for optimization to generate molecules with desirable properties, such as binding affinity and the logarithm of the partition coefficient between octanol and water. In addition, a memory storage network was added to increase the internal diversity of the generated molecules. For multi-objective optimization, we proposed a new approach which utilized the magnitude of different attribute reward values to assign different weights to molecular optimization. The proposed model not only solves the problem that the properties of the generated molecules are extremely biased towards a certain attribute due to the possible conflict between the attributes, but also improves various properties of the generated molecules compared with the traditional weighted sum and alternating weighted sum, among which the molecular validity reaches 97.3%, the internal diversity is 0.8613, and the desirable molecules increases from 55.9 to 92%.

Autophagy has drawn attention from the scientific community, mainly because of its significant advantages over chemotherapeutic processes. One of these advantages is its direct action on cancer cells, avoiding possible side effects, unlike chemotherapy, which reaches tumor cells and affects healthy cells in the body, leading to a great loss in the quality of life of patients. In this way, it is known that vanadium complex (VC) [VO(oda)(phen)] has proven inhibition effect on autophagy process in pancreatic cancer cells. Keeping that in mind, molecular dynamics (MD) simulations can be considered excellent strategies to investigate the interaction of metal complexes and their biological targets. However, simulations of this type are strongly dependent on the appropriate choice of force field (FF). Therefore, this work proposes the development of AMBER FF parameters for VC, having a minimum energy structure as a starting point, obtained through DFT calculations with B3LYP/def2-TZVP level of theory plus ECP for the vanadium atom. An MD simulation in vacuum was performed to validate the developed FF. From the structural analyses, satisfying values of VC bond lengths and angles were obtained, where a good agreement with the experimental data and the quantum reference was found. The RMSD analysis showed an average of only 0.3%. Finally, we performed docking and MD (120 ns) simulations with explicit solvent between VC and PI3K. Overall, our findings encourage new parameterizations of metal complexes with significant biological applications, as well as allow to contribute to the elucidation of the complex process of autophagy.

CONTEXT: [Formula: see text]-adenosine-methyltransferase (METTL3) is the catalytic domain of the 'writer' proteins which is involved in the post modifications of [Formula: see text]-methyladinosine ([Formula: see text]). Though its activities are essential in many biological processes, it has been implicated in several types of cancer. Thus, drug developers and researchers are relentlessly in search of small molecule inhibitors that can ameliorate the oncogenic activities of METTL3. Currently, STM2457 is a potent, highly selective inhibitor of METTL3 but is yet to be approved. METHODS: In this study, we employed structure-based virtual screening through consensus docking by using AutoDock Vina in PyRx interface and Glide virtual screening workflow of Schrodinger Glide. Thermodynamics via MM-PBSA calculations was further used to rank the compounds based on their total free binding energies. All atom molecular dynamics simulations were performed using AMBER 18 package. FF14SB force fields and Antechamber were used to parameterize the protein and compounds respectively. Post analysis of generated trajectories was analyzed with CPPTRAJ and PTRAJ modules incorporated in the AMBER package while Discovery studio and UCSF Chimera were used for visualization, and origin data tool used to plot all graphs. RESULTS: Three compounds with total free binding energies higher than STM2457 were selected for extended molecular dynamics simulations. The compounds, SANCDB0370, SANCDB0867, and SANCDB1033, exhibited stability and deeper penetration into the hydrophobic core of the protein. They engaged in relatively stronger intermolecular interactions involving hydrogen bonds with resultant increase in stability, reduced flexibility, and decrease in the surface area of the protein available for solvent interactions suggesting an induced folding of the catalytic domain. Furthermore, in silico pharmacokinetics and physicochemical analysis of the compounds revealed good properties suggesting these compounds could serve as promising MEETL3 entry inhibitors upon modifications and optimizations as presented by natural compounds. Further biochemical testing and experimentations would aid in the discovery of effective inhibitors against the berserk activities of METTL3.

CONTEXT: In this discussion, we began building two model, S2O + CHCl•- and O3 + CHCl•-, using DFT-BHandHLYP method, to study their reactions mechanisms on singlet PES. For this purpose, we hope to explore the effects of the difference between sulfur and oxygen atoms on the CHCl•- anion. Experimentalists and computer scientists may utilize the collected data to generate a wide range of hypotheses for experimental phenomena and predictions, allowing them to realize their full potential. METHODS: The ion-molecule reaction mechanism of CHCl•- with S2O and O3 was studied using the DFT-BHandHLYP level of theory with the aug-cc-pVDZ basis set. Our theoretical findings show that Path 6 is the favored reaction pathway for CHCl•- + O3 reaction as identified by the O-abstraction reaction pattern. Comparing to the direct H- and Cl-abstraction mechanisms, the reaction (CHCl•- + S2O) prefers the intramolecular SN2 reaction pattern. Moreover, the calculated results demonstrated that the CHCl•- + S2O reaction is thermodynamically more favorable than the CHCl•- + O3 reaction, which is kinetically more advantageous. As a result, if the required reaction condition in the atmospheric process is met, the O3 reaction will happen more effectively. In terms of kinetics and thermodynamics viewpoints, the CHCl•- anion was very effective in eliminating S2O and O3.

CONTEXT: Squamous cell carcinoma (SCC) is the second most common type of skin cancer caused by malignant keratinocytes. Multiple studies have shown that protein mutations have a significant impact on the development and progression of cancer, including SCC. We attempted to decode the effect of single amino acid mutations in the Bruton's tyrosine kinase (BTK) protein in this study. Molecular dynamic (MD) simulations were performed on selected deleterious mutations of the BTK protein, revealing that the variants adversely affect the protein, indicating that they may contribute to the prognosis of SCC by making the protein unstable. Then, we investigated the interaction between the protein and its mutants with ibrutinib, a drug designed to treat SCC. Even though the mutations have deleterious effects on protein structure, they bind to ibrutinib similarly to their wild type counterpart. This study demonstrates that the effect of detected missense mutations is unfavorable and can result in function loss, which is severe for SCC, but that ibrutinib-based therapy can still be effective on them, and the mutations can be used as biomarkers for Ibrutinib-based treatment. METHODS: Seven different computational techniques were used to compute the effect of SAVs in accordance with the experimental requirements of this study. To understand the differences in protein and mutant dynamics, MD simulation and trajectory analysis, including RMSD, RMSF, PCA, and contact analysis, were performed. The free binding energy and its decomposition for each protein-drug complex were determined using docking, MM-GBSA, MM-PBSA, and interaction analysis (wild and mutants).

CONTEXT: In this research, CO2 and NO2 adsorption on doped nanographene (NG) sheets with transition metals (Fe, Ni, Zn) and (Mn, Co, Cu), respectively, have been applied for scavenging of these toxic gases as the environmental pollutants. The values of changes of atomic charge density have illustrated a more significant charge transfer for Ni-doped C-NG through CO2 adsorption and a more remarkable charge transfer for Co-doped C-NG through NO2 adsorption. The data of NMR spectroscopy has depicted several fluctuations around the graph of Zn-doped on the nanographene surface. The thermodynamic results from IR spectroscopy have indicated that [Formula: see text] values are almost similar for doped metal transitions of Mn, Co, and Cu on the C-NG nanosheet, while [Formula: see text] has the largest gap of Gibbs free energy adsorption with dipole moment. METHODS: The Langmuir adsorption model with a three-layered ONIOM using CAM-B3LYP functional accompanying LANL2DZ, EPR-III and 6-31 + G (d,p) basis sets due to Gaussian 16 revision C.01 program on the complexes of CO2 → (Fe, Ni, Zn) and NO2 → (Mn, Co, Cu) doped on the C-NG has been accomplished. Then, NMR and IR spectroscopy, nuclear quadrupole resonance, and natural bond orbital analysis have been accomplished for evaluating chemical shielding tensors, thermodynamic properties, electric potential, and occupancy fluctuation through bond orbitals, respectively. In addition, frontier orbitals of LUMO, HOMO, and also a series of chemical reactivity parameters have been calculated. Finally, time-dependent-DFT method due to UV-VIS spectrums has been accomplished to discern the low-lying excited states of CO2 and NO2 adsorption on the (Fe, Ni, Zn) and (Mn, Co, Cu), respectively, doped C-NG sheet.

BACKGROUND: Drug discovery processes, such as new drug development, drug synergy, and drug repurposing, consume significant yearly resources. Computer-aided drug discovery can effectively improve the efficiency of drug discovery. Traditional computer methods such as virtual screening and molecular docking have achieved many gratifying results in drug development. However, with the rapid growth of computer science, data structures have changed considerably; with more extensive and dimensional data and more significant amounts of data, traditional computer methods can no longer be applied well. Deep learning methods are based on deep neural network structures that can handle high-dimensional data very well, so they are used in current drug development. RESULTS: This review summarized the applications of deep learning methods in drug discovery, such as drug target discovery, drug de novo design, drug recommendation, drug synergy, and drug response prediction. While applying deep learning methods to drug discovery suffers from a lack of data, transfer learning is an excellent solution to this problem. Furthermore, deep learning methods can extract deeper features and have higher predictive power than other machine learning methods. Deep learning methods have great potential in drug discovery and are expected to facilitate drug discovery development.

CONCEPT: MNDO-based semi-empirical methods in quantum chemistry have found widespread application in the modelling of large and complex systems. A method for the analytic evaluation of first and second derivatives of molecular properties against semi-empirical parameters in MNDO-based NDDO-descendant models is presented, and the resultant parameter Hessian is compared against the approximant currently used in parameterization for the PMx models. METHODS: As a proof of concept, the exact parameter Hessian is employed in a limited reparameterization of MNDO for the elements C, H, N, O and F using 1206 molecules for reference data (heats of formation, ionization energies, dipole moments and reference geometries). The correctness of our MNDO implementation was verified by comparing the calculated molecular properties with the MOPAC program.

Cases of drug-resistant tuberculosis (TB) have increased worldwide in the last few years, and it is a major threat to global TB control strategies and the human population. Mycobacterium tuberculosis is a common causative agent responsible for increasing cases of TB and as reported by WHO, approximately, 1.5 million death occurred from TB in 2020. Identification of new therapies against drug-resistant TB is an urgent need to be considered primarily. The current investigation aims to find the potential biogenic chalcone against the potential targets of drug-resistant TB via in silico approach. The ligand library of biogenic chalcones was screened against DprE1. Results of molecular docking and in silico ADMET prediction revealed that ZINC000005158606 has lead-like properties against the targeted protein. Pharmacophore modeling was done to identify the pharmacophoric features and their geometric distance present in ZINC000005158606. The binding stability study performed using molecular dynamics (MD) simulation of the DprE1-ZINC000005158606 complex revealed the conformational stability of the complex system over 100 ns with minimum deviation. Further, the in silico anti-TB sensitivity of ZINC000005158606 was found to be higher as compared to the standards against Mycobacterium tuberculosis. The overall in silico investigation indicated the potential of identified hit to act as a lead molecule against Mycobacterium tuberculosis.

The integrants of proteins, i.e., amino acids, have grossed exceptional recognition for their applications towards designing imminent switching devices. Among 20 amino acids, L-Lysine (i.e., positively charged) has the highest number of CH2 chains, and such chains affect the rectification ratio in several biomolecules. Towards molecular rectification, we investigate the transport parameters of L-Lysine in conjunction with five different coinage metal electrodes, i.e., Au, Ag, Cu, Pt and Pd to form five distinct devices. We deputize the NEGF-DFT formulism for computing conductance, frontier molecular orbitals, current-voltage, and molecular projected self-Hamiltonian calculations using a self-consistent function. We focus on the most widely used electron exchange correlation combination, i.e., the PBE version of GGA with DZDP basis set. The molecular devices under inquisition exhibit phenomenal rectification ratios (RR) in conjunction with negative differential resistance (NDR) regimes. The nominated molecular device offers a substantial rectification ratio of 45.6 with platinum electrodes and a prominent peak to valley current ratio of 1.78 with copper electrodes. We deduce from these findings that L-Lysine based molecular devices would implicit in future bio-nanoelectronic devices. The OR and AND logic gates are also proposed hinged on highest rectification ratio of L-Lysine-based devices.

CONTEXT: A steam-rich environment is a more promising application scenario for future coal-fired processes, while active sites are the key factor that determines the reactivity of carbonaceous fuels. The steam gasification process of carbon surfaces with different numbers of active sites (0, 12, 24, 36) was simulated using reactive molecular dynamics in the present study. The temperature for the decomposition of H2O and the gasification of carbon is determined using temperature-increasing simulation. The decomposition of H2O was influenced by two driving forces, thermodynamics and active sites on the carbon surface, which dominated the different reaction stages, leading to the observed segmentation phenomenon of the H2 production rate. The existence and number of initial active sites have a positive correlation with both two stages of the reaction, greatly reducing the activation energy. Residual OH groups play an important role in the gasification of carbon surfaces. The supply of OH groups through the cleavage of OH bonds in H2O is the rate-limiting step in the carbon gasification reaction. The adsorption preference at carbon defect sites was calculated using density functional theory. Two stable configurations (ether & semiquinone groups) can be formed with O atoms adsorbed on the carbon surface according to the number of active sites. This study will provide further insights into the tuning of active sites for advanced carbonaceous fuels or materials. METHODS: The large-scale atomic/molecule massively parallel simulator (LAMMPS) code combined with the reaction force-field method was used to carry out the ReaxFF molecular dynamics simulation, where the ReaxFF potentials were taken from Castro-Marcano, Weismiller and William. The initial configuration was built using Packmol, and the visualization of the calculation results was realized through Visual Molecular Dynamics (VMD). The timestep was set to 0.1 fs to detect the oxidation process with high precision. PWscf code in QUANTUM ESPRESSO (QE) package, was used to evaluate the relative stability of different possible intermediate configurations and the thermodynamic stability of gasification reactions. The projector augmented wave (PAW) and the generalized gradient approximation of Perdew-Burke-Ernzerhof (PBE-GGA) were adopted. Kinetic energy cutoffs of 50 Ry and 600 Ry, and a uniform mesh of 4 × 4 × 1 k-points were used.

The anticorrosion performance of silane-modified chitosan/epoxy primer coatings was evaluated using quantum chemical computations (QCC) and molecular dynamics simulation (MDS) techniques. The objective was to appraise the molecular/atomistic level performance of silane-modified chitosan/epoxy primer coating system on mild steel in saline water to be able to design robust anticorrosion epoxy nanocomposite primer coating for marine application. The QCC showed that quantum parameters for (3-aminopropyl) trimethoxy silane-modified chitosan nanocluster (AMCN) are optimum and therefore correspond to high corrosion protective capability. The adsorption energies (Eads) for AMCN/epoxy, tetraethoxysilane-modified chitosan/epoxy, chitosan-modified epoxy, and unmodified epoxy coatings were found to be - 3094.65, - 2,630.00, - 2,305.77, and - 1,189.33 kcal/mol, respectively. The high negative value of Eads indicates the coating molecules interacted and adsorbed strongly on the mild steel surface. Hence, AMCN/epoxy coating is potentially most corrosion-resistant than the others. Further, it is established that shorter bond length corresponds to higher bond strength and therefore indicates chemical interaction. Thus, the radial distribution function showed the bond lengths between atoms of the AMCN and mild steel surfaces were shorter than those of other molecules. Overall, AMCN/epoxy coating molecules possess good anticorrosion properties and therefore would perform well if deployed for service in saline environments.

CONTEXT: Molecular dynamics-based investigation has been carried out to simulate the nano-indentation loading in crystalline Al-amorphous Al90Sm10 metallic glass (MG) with an aim to investigate the effect orientation of crystalline-amorphous (C/A) interface orientation on the nano-indentation behavior of the C/A Al-Al90Sm10 nanolaminate for varying indenter speeds. Post-analysis techniques like adaptive-common neighbor analysis (a-CNA), atomic strain, dislocation extraction algorithm (DXA), and Voronoi polyhedral analysis (VP) have been employed to capture the structural evolution during simulated nano-indentation loading. C/A Al-Al90Sm10 nanolaminate with C/A interface orientated perpendicular to the indenter exhibits the presence of elastic regime followed by plastic curve, whereas load versus depth curve behaves plastically since the beginning in case of C/A Al-Al90Sm10 nanolaminate with C/A interface orientated parallel to the indenter. The dislocation density growth is slower in case of C/A Al-Al90Sm10 nanolaminate with C/A interface orientated perpendicular to the indenter attributed to the sinking of dislocations into MG counterpart of the nanolaminate, thereby triggering shear transformation zone activation. Whereas, the dislocation generation is delayed in case of C/A Al-Al90Sm10 nanolaminate with C/A interface orientated parallel to the indenter by virtue of amorphous Al90Sm10 MG coating on crystalline Al but is extensive and rapid. The disintegration of ICO-like structures and mixed clusters and growth of crystal-like clusters is discernible in C/A Al-Al90Sm10 nanolaminate with C/A interface orientated perpendicular to the indenter. On the other hand, the VP population exhibits cyclic variation in C/A Al-Al90Sm10 nanolaminate with C/A interface orientated parallel to the indenter. A transformation pathway of VPs has been mapped out for C/A Al-Al90Sm10 nanolaminate under nano-indentation loading. METHODS: The simulations have been carried out by employing Molecular Dynamics using the Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) platform. Post-analysis techniques like adaptive-common neighbor analysis (a-CNA), atomic strain, dislocation extraction algorithm (DXA), and Voronoi polyhedral analysis (VP) have been employed to capture the structural evolution during simulated nano-indentation loading.

CONTEXT: Based on the first-principles calculations, this paper investigates the structural, elastic, electronic, and optical properties of albite and kaolinite, respectively. It is determined that both of them show structural stability, mechanical stability, and brittleness by calculating formation enthalpy, phonon dispersion, elastic, and mechanically relevant properties. Both materials are insulators with an indirect bandgap. By calculating the TDOS and PDOS, the main characteristics of the electronic structure of NaAlSi3O8 come from O-2p and Si-3p states, O-2p, and Al-3p states hybridization, similar to Al4[Si4O10](OH)8. The covalence of Si-O bonds in NaAlSi3O8 is greater than Al-O bonds, and the covalent property sequence of Si-O bands in NaAlSi3O8 is Si2-O3 > Si1-O4 > Si2-O2 > Si1-O8 > Si1-O6 > Si3-O2 > Si3-O4. The optical anisotropy of NaAlSi3O8 and Al4[Si4O10](OH)8 is analyzed. METHODS: First-principles density functional theory (DFT) calculation was carried out by the CASTEP computer program. The GGA-PW91 exchange-correlation was used. The energy convergence tolerance, the maximum force, and the maximum displacement were set in the calculation.

CONTEXT: RARγ is a therapeutic target for many skin diseases and has potential in cancer treatment. In the current study, we put forward a comprehensive structure-activity relationship study of third and fourth generations of RARγ agonists, addressing multiple crystal structures of RARγ complexes and approved drugs. Adapalene and Trifarotene, through hybrid strategies including protein contacts Atlas analysis, molecular docking, dynamics simulations, MM-GBSA, ASM, and pharmacophore modeling. Our result revealed crucial amino acids Arg267, Ser278, Phe288, Phe230, Met272, Leu271, and Leu268 within the RARγ pocket, as well as pharmacophore features such as two hydrophobic groups, two aromatic rings, and negative ionic features, which are essential for the binding of RARγ agonists. Based on this study, the binding mechanism of RARγ agonists was elucidated, which will be helpful for the rational design of new RARγ agonists for skin diseases and cancer treatment. METHODS: In this study, Schrödinger suite 2021-2 with OPLS_4 force field, Discovery Studio program 3.0, LigandScout 4.3, and PyMOL are utilized in the investigation.

OBJECTIVE: The COVID-19 epidemic is raging around the world, with the emergence of viral mutant strains such as Delta and Omicron, posing severe challenges to people's health and quality of life. A full understanding life cycle of the virus in host cells helps to reveal inactivation mechanism of antibody and provide inspiration for the development of a new-generation vaccines. METHODS: In this work, molecular recognitions and conformational changes of SARS-CoV-2 spike protein mutants (i.e., Delta, Mu, and Omicron) and three essential partners (i.e., membrane receptor hACE2, protease TMPRSS2, and antibody C121) both were compared and analyzed using molecular simulations. RESULTS: Water basin and binding free energy calculations both show that the three mutants possess higher affinity for hACE2 than WT, exhibiting stronger virus transmission. The descending order of cleavage ability by TMPRSS2 is Mu, Delta, Omicron, and WT, which is related to the new S1/S2 cutting site induced by transposition effect. The inefficient utilization of TMPRSS2 by Omicron is consistent with its primary entry into cells via the endosomal pathway. In addition, RBD-directed antibody C121 showed obvious resistance to Omicron, which may have originated from high fluctuation of approaching angles, high flexibility of I472-F490 loop, and reduced binding ability. CONCLUSIONS: According to the overall characteristics of the three mutants, high infectivity, high immune escape, and low virulence may be the future evolutionary selection of SARS-CoV-2. In a word, this work not only proposes the possible resistance mechanism of SARS-CoV-2 mutants, but also provides theoretical guidance for the subsequent drug design against COVID-19 based on S protein structure.

CONTEXT: In guest-host interactions, guest molecules used for hydrogen bonding potential of clathrate hydrate cages are involved as "promoters" for hydrogen or methane storage. Among the promoter molecules, there are pinacolone and tert-butylmethyl ether containing oxygen atom, and tert-butyl amine among those containing nitrogen atom. The dimer and trimer interactions of these molecules with the water clusters were investigated. The cooperativity effect, which is a measure of the hydrogen bonding of these oxygen and nitrogen-containing complexes, was calculated and these complexes were analyzed. Moreover, molecular electrostatic potential (MEP) analysis was performed to determine intermolecular interactions. Clusters of several molecules may seem like a non-significant state of matter; however, in systematic studies with small clusters, important results can be obtained. Therefore, it is very useful to work with clusters to understand the properties of the dense phase, and this study aimed to examine the properties of structures, energies, infrared vibration frequencies, and topological parameters, which develop as a result of the interaction of structures in different clusters with water molecules. METHODS: The MP2 level was performed using aug-cc-pVDZ basis set calculations for this study. Tight converting criteria were used in the optimization step. Harmonic vibrational modes were calculated at the MP2/aug-cc-pVDZ level. Each minima obtained from the MP2 level was subjected to single-point energy calculations using CCSD(T) levels with the aug-cc-pVDZ basis set by the Gaussian16 package program suite. The topological analyses were performed with non-covalent interaction (NCI). MEP surface of the complex was also composed by Gaussian program using the optimized geometry at a MP2/aug-cc-pvdz level.

CONTEXT: A large number of heterocyclic compounds are used as drugs, mainly due to the duality of lipophilicity playing in hydrophobic interactions and solubility with at least one hydrogen bond acceptor. The study of electronic properties is then important to better understand not only these charge distribution effects but also some other physicochemical properties involved in bioactivity to directly assess the bioavailability of these compounds and a possible classification in related applications. Phytomolecules such as chromenes are very accessible molecules exhibiting a bioactivity. Our study is focused on the impact of a number of functional groups acting on some 2,2-dimethylchromene derivatives, namely their global reactivity from the frontier molecular orbitals and local reactivity from the Fukui functions, where the carbonyl group acting as an electron withdrawal group has the most relevant effect, the solubility from the partition coefficient Log P strongly depending on the charge distribution and electronegative sites, the optical effects from the delocalization in the vinyl group, as well as the evaluation of the entropy associated with the molecular flexibility also acting on the bioactivity. Despite the effects of the wave function or density methods on the order of magnitude of these properties, these compounds are consistent with the rules for a potential oral drug candidate. METHODS: The calculations of the electronic properties were performed through two levels of theory: Hartree-Fock level as a wave function-based method as an ab initio reference including some physically consistent eigenvalues and density functional theory DFT as a correlation consistent method using different functionals: hybrid or with a long-range correction. The basis set used is a 6-311++G(d,p) Pople basis set including diffuse and polarization basis functions. The basis set is adapted to the size of the molecules and consequently to the degree of electronic localization. Gaussian 09 software was used for the computation.

CONTEXT: The structures of Ag2n-1Sn- (n = 2-11) clusters are obtained by the combination of genetic algorithm (GA) and density functional theory (DFT). All the global minimum structures prefer hollow polyhedral structures, in which S-Ag-S element, triangular Ag3S3 and tetragonal Ag4S4 units present to stabilize the structures. The S atoms in the structures appear in μ3-S or μ4-S form. Adiabatic and vertical electron affinities of the clusters have been obtained, which reveals that they increases as cluster size. Stability analysis shows that Ag9S5- and Ag19S10- have special stability. The HOMO, LUMO orbitals of the clusters are obtained and the orbital components of them are calculated. The HOMO orbitals are mainly from the p orbitals of S atoms, whereas the s, p and d orbitals of Ag atoms contribute much bigger than the p orbitals of S atoms for LUMO orbitals. The orbital delocalization indexes (ODI) of the HOMOs and LUMOs are calculated, and the small ODIs of the HOMOs and LUMOs for n = 4-10 reveal that these orbitals are highly delocalized. By studying the projected density of states and molecular orbitals of Ag9S5- and Ag19S10- clusters, it is found that their molecular orbitals have superatomic properties. Superatomic properties play an important role in stabilizing clusters. METHODS: This work used combined genetic algorithm and density functional theory (GA-DFT), and PBE0/Lanl2tz(Ag)/6-311G(d,p)(S) method to optimize the structures. Gaussian 16 program, Gauss view 6.0.16 program and Multiwfn 3.8 code are the softwares used.

CONTEXT: The mechanical properties and deformation mechanisms of CoCrNi medium-entropy alloy are studied through molecular dynamics simulations. The effects of temperature and average grain size on the elastic modulus, Poisson's ratio, yield stress, and maximum flow stress are investigated. METHODS: The constant pressure molecular dynamics method is used to calculate the elastic modulus and Poisson's ratio of the alloy at different temperatures and average grain sizes. Simple tension simulations are conducted to determine the yield stress and maximum flow stress as a function of average grain size. The study also analyzes the dislocation behavior near grain boundaries at different temperatures using molecular dynamics simulations. The Hall-Petch and inverse Hall-Petch relationships are employed to describe the grain size-dependent deformation behavior of the alloy.

OBJECTIVE: The aggregation of alpha-synuclein (α-syn) is closely related to the pathogenesis and dysfunction of Parkinson's disease. METHODS: To investigate the potential of nanoparticlemediated therapy, the interactive mechanism between α-syn and n-myristyltrimethylammonium bromide (MTAB) Gold nanoparticles (AuNPs) with different diameters was explored by molecular dynamics simulations. RESULTS: The results indicated that there was a directional interaction between α-syn and n-MTAB AuNPs, in which the driving force for the binding of the C-terminus in α-syn came from electrostatic interactions and the nonamyloid β component (NAC) domain exhibited weak hydrophobic interactions as well as electrostatic interaction, thereby preventing α-syn aggregation. Energy statistics and analysis showed that for 5-MTAB AuNPs, acidic amino acids such as Glu and Asp played a very important role. CONCLUSIONS: This study not only demonstrated a theoretical foundation for the behavior of biomolecules directionally adsorbed on the surface of biofunctional nanoparticles but also indicated that 5-MTAB AuNPs may be a potential inhibitor against α-syn protein aggregation.

CONTEXT AND RESULTS: Aromaticity is a fundamental chemical concept that has been widely used in explaining the reactivity, stability, structure, and magnetic properties of many molecules such as conjugated macrocycles, metal heterocyclic compounds, and certain metal clusters. Porphyrinoids (including porphyrin) are of particular interest in terms of diverse aromaticity. Various indices therefore have been used to predict the aromaticity of porphyrin-like macrocycles. However, the reliability of these indices for porphyinoids is always questionable. In order to assess the performance of the indices, we have selected six representative indices to predict the aromaticity of 35 porphyrinoids. The calculated values were then compared with the corresponding results obtained from experiments. Our studies suggest that the theoretical prediction by nucleus independent chemical shifts (NICS), topology of the induced magnetic field (TIMF), anisotropy of the induced current density (AICD), and gauge including magnetically induced current method (GIMIC) are essentially consistent with experimental evidence in all 35 cases and thus are preferred indices. COMPUTATIONAL AND THEORETICAL TECHNIQUES: Based on density functional theory, the performance of the NICS, TIMF, AICD, GIMIC, harmonic oscillator model of aromaticity (HOMA), and multicenter bond order (MCBO) indices were evaluated theoretically. Molecular geometries were optimized at the M06-2X/6-311G** level. NMR calculations using GIAO or CGST method were performed at the M06-2X/6-311G** level. The above calculations were carried out using Gaussian16 suite. The TIMF, GIMIC, HOMA, and MCBO indices were obtained using the Multiwfn program. The AICD outputs were visualized using the POV-Ray software.

CONTEXT: In this work, 24 new nitrogen-rich fused-ring energetic metal complexes were designed based on the double fused-ring insensitive ligands strategy. First, 7-nitro-3-(1H-tetrazol-5-yl)-[1,2,4]triazolo[5,1-c][1,2,4]triazin-4-amine and 6-amino-3-(4H,8H-bis([1,2,5]oxadiazolo)[3,4-b:3',4'-e]pyrazin-4-yl)-1,2,4,5-tetrazine-1,5-dioxide were linked together by coordinating with metals cobalt and copper. Then, three energetic groups (NH2, NO2, and C(NO2)3) were introduced into the system to modify the structure and adjust the performance. Then, their structures and properties were investigated theoretically; the effects of different metals and small energetic groups were studied also. Finally, 9 compounds which have both higher energy and lower sensitivity than the famous high energy compound compound 1,3,5,7-tetranitro-1,3,5,7-tetrazocine were selected out. In addition, it was found that copper, NO2, and C(NO2)3 could increase the energy while cobalt and NH2 would be helpful for reducing the sensitivity. METHODS: Calculations were performed at the TPSS/6-31G(d) level by using the Gaussian 09 software.

INTRODUCTION: Nowadays, propulsion materials are receiving increased attention as an important component in electric motors. So, awareness of their chemical reactivity and geometric and electronic structures can help to make materials with higher quality and efficiency. In this study, we have proposed novel glycidyl nitrate copolymers (GNCOPs) and meta-substituted derivatives as propulsion materials. METHOD: Based on density functional theory (DFT) method, chemical reactivity indices have been calculated for predicting their behavior in burning process. RESULT AND DISSCUSSION: Adding functional groups changes reactivity of the GNCOP compound, especially, in the -CN functional group, chemical potential, chemical hardness, and electrophilicity change -0.374, +0.007, and +1.342eV, respectively. In addition, these compounds have dual properties in interaction with oxygen molecule. Optoelectronic study in time-dependent DFT framework shows that there are three peaks with significant excitations. CONCLUSION: In conclusion, adding functional group into the GNCOPs can introduce new materials with high energetic properties.

Ribosomal protein S6 kinase beta-1 (S6K1) is considered a potential target for the treatment of various diseases, such as obesity, type II diabetes, and cancer. Development of novel S6K1 inhibitors is an urgent and important task for the medicinal chemists. In this research, an effective ensemble-based virtual screening method, including common feature pharmacophore model, 3D-QSAR pharmacophore model, naïve Bayes classifier model, and molecular docking, was applied to discover potential S6K1 inhibitors from BioDiversity database with 29,158 compounds. Finally, 7 hits displayed considerable properties and considered as potential inhibitors against S6K1. Further, carefully analyzing the interactions between these 7 hits and key residues in the S6K1 active site, and comparing them with the reference compound PF-4708671, it was found that 2 hits exhibited better binding patterns. In order to further investigate the mechanism of the interactions between 2 hits and S6K1 at simulated physiological conditions, the molecular dynamics simulation was performed. The ΔGbind energies for S6K1-Hit1 and S6K1-Hit2 were - 111.47 ± 1.29 and - 54.29 ± 1.19 kJ mol-1, respectively. Furthermore, deep analysis of these results revealed that Hit1 was the most stable complex, which can stably bind to S6K1 active site, interact with all of the key residues, and induce H1, H2, and M-loop regions changes. Therefore, the identified Hit1 may be a promising lead compound for developing new S6K1 inhibitor for various metabolic diseases treatment.

CONTEXT: Viscosity and viscosity index are the crucial properties of lubricant base stocks. Molecular dynamics simulation and quantum calculation were used to simulate the five isomers of C26H54 to study the intrinsic relationship between viscosity, viscosity index, and the molecular structure of isoalkanes. The results showed that the intermolecular interaction energy and the volume of rigid-like groups were the intrinsic factors that affected the viscosity and which could describe the viscosity quantitatively. The molecule conformation was studied by calculating the rotational energy barrier of the dihedral angle in the isoalkane molecule, and combined with molecular dynamics, the effect of temperature on the molecular conformation at 313 K and 373 K was further investigated. The α, β, and γ carbon atoms adjacent to the tertiary carbon in the isoalkane molecule were difficult to rotate due to steric hindrance and could be regarded as rigid-like groups at 313 K. The tertiary carbon and the three adjacent carbon atoms formed a regular tetrahedral rigid-like group at 373 K. The changes in the intermolecular interaction energy and the volume of the rigid-like group with temperatures could better describe the viscosity index and reveal the fundamental reasons that affect the viscosity and the viscosity index. The molecular-level understanding of the relationship between the molecular structure and properties of isoalkanes provided theoretical support and scientific guidance for designing isoalkane molecules with specific properties. METHODS: Molecular dynamics simulation and quantum calculation were performed using Material Studio 8.0 software. The Amorphous Cell module was used to create an amorphous cell. The Foricite module was used for molecular dynamics simulation; the forcefield was assigned as COMPASS II. Nose-Hoover thermostat and Berendsen barostat were applied to maintain the temperature and pressure, respectively. To describe the non-bond interactions, the Ewald method was applied to calculate the van der Waals and electrostatic interactions. The Conformers module was used to study the conformation and the Dmol3 module was used to calculate the conformational energy with fine quality; the functional of GGA-PW91 and the basis set of DNP were used to calculate the energy.

Beta-tubulin (TUBB) protein is one of the components of the microtubule cytoskeleton that plays a critical role in the central nervous system. Genetic variants of TUBB cause cortical dysplasia, a developmental brain defect implicated in axonal guidance and the neuron migration. In this study, we assess pathogenic variants (Q15K, Y222F, M299V, V353I, and E401K) of TUBB protein and compared with non-pathogenic variant G235S to determine their impact on protein dynamic to cause cortical dysplasia. Among the analyzed variants, Q15K, Y222F, M299V, and E401K were noticed to have deleterious effect. Then, variant structures were modeled and their affinity with their known cofactor Guanosine-5'-triphosphate (GTP) was assessed which showed diverse binding energies ranged between (-7.436 to -6.950 kcal/mol) for the variants compared to wild-type (-7.428 kcal/mol). Finally, the molecular dynamics simulation of each variant was investigated which showed difference in trajectory between the pathogenic and non-pathogenic variant. Our analysis suggests change in amino acid residue of TUBB structure has notably affects the protein flexibility and their interactions with known cofactor. Overall, our findings provide insight on the relationship between TUBB variants and their structural dynamics that may cause diverse effects leading to cortical dysplasia.

Through utilizing density functional theory (DFT), the current work investigates the potential uses of Al24P24 fullerene for detecting CS2, H2S, SO2, and COS. The interaction order for the stability of these gases was SO2 > H2S > COS > CS2. The moment of electric dipole and molecules' adsorption energy seems correlated. Al24P24 fullerene is regarded as an electronic sensor of the Ф-type for detecting SO2 and CS2. According to the findings, CS2 and SO2 might act as Al24P24 fullerenes when H2S is present. Nevertheless, we cannot presume it to be a COS and H2S sensor of Ф-type. At room temperature, the fullerene of Al24P24 has a quick recovery time of 0.50 μs and 0.17 s in CS2 and SO2 desorption from the surface. It can thus be inferred that it has the ability to function in moist media.

CONTEXT: Leishmaniasis is a group of vector-borne infectious diseases caused by over 20 pathogenic Leishmania species that are endemic in many tropical and subtropical countries. The emergence of drug-resistant strains, the adverse side effects of anti-Leishmania drugs, and the absence of a preventative vaccination strategy threaten the sensitive population. Recently, many groups of researchers have exploited the field of reverse vaccinology to develop vaccines, focusing chiefly on inducing immunity against either visceral or cutaneous leishmaniasis. METHODS: This present work involves retrieving twelve experimentally validated leishmanial antigenic protein sequences from the UniProt database, followed by their antigenicity profiling employing ANTIGENpro and Vaxijen 2.0 servers. MHC-binding epitopes for the same were predicted using both NetCTL 1.2 and SYFPEITHI servers, while epitopes for B cell were computed using ABCpred and BepiPred 2.0 servers. The screened epitopes with significantly higher scores were utilized for designing the vaccine construct with appropriate linkers and natural adjuvant. The secondary and tertiary structures of the synthetic peptide were determined by conditional random fields, shallow neural networks, and profile-profile threading alignment with iterative structure assembly simulations, respectively. The 3-D vaccine model was validated through CASP10-tested refinement and the MolProbity web server. Molecular docking and multi-scale normal mode analysis simulation were performed to analyze the best vaccine-TLR complex. Finally, computational immune simulation findings revealed promising cellular and humoral immune responses, suggesting that the engineered chimeric peptide is a potential broad-spectrum vaccine against visceral and cutaneous leishmaniasis.

CONTEXT: The molecular design of spatially preorganized molecules is one of the critical issues in organic chemistry. Molecular recognition and multipoint binding define them. They organize nanoscale assemblies and devices and stably form host-guest inclusion complexes. Not only is this kind of research important in theory but it also has applications. They are used to create the basic elements of sensory devices: elements of cellular electronics, functional nanofilms and coatings, molecular switches, etc. Thiacalix[4]arenes are a useful molecular platform for constructing a wide range of preorganized receptor structures. This research aims to examine the structure and spectra of distally substituted para-tert-butylthiacalix[4]arene aliphatic (C1) and aromatic (C2) esters. The comparison of the spectra of C1, C2, and C3 makes it possible to reveal the structures and H-bonds of these compounds. The structures and H-bonds of these compounds can be seen by analyzing the spectra of C1, C2, and C3. Calculations were made for the spectra of various C1 and C2 molecule conformations. The most stable conformation for C1 and C2 molecules is a distorted cone 2 (DC2) with the same ester group orientation. The pinched cone (PC) conformation is the most unstable. Thiacalixarene molecules' cavities shrink from 3.61 to 3.57 Å when aromatic ester groups take the place of aliphatic ester groups. Two OH groups are linked to an oxygen atom in the DC1 and DC2 conformations of the C1 and C2 molecules. H-bonds in C1 and C2 molecules affect the supramolecular characteristics of these molecules. A drop in ionization energy and increases in electron affinity, chemical potential, softness, electrophilicity index, and dipole moment occur when aliphatic esters are replaced with aromatic ones. METHODS: Disubstituted aliphatic and aromatic esters' IR, Raman, and NMR spectra have been investigated. The DFT/B3LYP/6-311G(d,p) method and the GAUSSIAN 09W software were used to determine the vibrational spectra of molecules and optimize their geometry. A gauge-independent (GIAO) approach was used to determine chemical shifts in the NMR spectra with respect to tetramethylsilane.

The structured abstract is combined from two parts: CONTEXT: The adsorption behavior of amphetamine (AMP) on the surface of ABW-aluminum silicate zeolite was implemented with a computational depiction. Studies of the electronic band structure (EBS) and density of states (DOS) were conducted to demonstrate transition behavior attributed to aggregate-adsorption interaction. Thermodynamic illustration of the studied adsorbate was studied to investigate the structural behavior of the adsorbate on the surface of the zeolite adsorbent. The best investigated models were assessed with adsorption annealing calculations related to adsorption energy surface. The periodic adsorption-annealing calculation model predicted a highly stable energetic adsorption system based on total energy, adsorption energy, rigid adsorption energy, deformation energy, and dEad/dNi ratio. METHODS: Cambridge sequential total energy package (CASTEP) based on density functional theory (DFT), under Perdew-Burke-Ernzerhof (PBE) basis set, was used to depict the energetic levels of the adsorption mechanism between AMP and ABW-aluminum silicate zeolite surface. DFT-D dispersion correction function was postulated for weakly interacted systems. Structural and electronic elucidations were described with geometrical optimization, FMOs, and MEP analyses. Thermodynamic parameters such as entropy, enthalpy, Gibbs free energy, and heat capacity over temperature dependence studied the conductivity behavior over localized energetic states based on Fermi level and described the disorder degree of the system.

CONTEXT: In 2000, a remarkably simple relationship was introduced, which connected the calculated geometries of isomolecular states of three different multiplicities. These encompass a ground single state, the first excited triplet state, as well as related radical anion and radical cation. The rule allows the prediction of the geometry of one of the species if the three remaining ones are known. Here, we verify the applicability of this bond length rule for two small planar cyclic organic molecules, i.e., benzene and cyclobutadiene, which stand as prototypical examples of, respectively, aromatic and antiaromatic systems. We see that the rule works fairly well to benzene, and it works independently for quinoid as well as for anti-quinoid minima, despite the fact that radical anion species poses challenges for correct theoretical description. METHODS: To obtain chosen electronic state equilibrium geometries, three types of computational approaches were utilized: fast and efficient density functional theory DFT, the coupled cluster method CC2, the complete active space self-consistent field (CASSCF) approach, and the most accurate but also resource-consuming perturbation theory with multireference wavefunction (CASPT2) with a default value and without IPEA-shift. Dunning and co-workers correlation-consistent basis sets (aug-)cc-pVXZ (X = D, T, Q) were employed. Gaussian 16 revision A.03, Turbomole 7.1, and Molcas 8.0 computational software were used.

Anthocyanidins, leucoanthocyanidins, and flavonols are natural compounds mainly known due to their reported biological activities, such as antiviral, antifungal, anti-inflammatory activities, and antioxidant activity. In the present study, we performed a comparative structural, conformational, electronic, and nuclear magnetic resonance analysis of the reactivity of the chemical structure of primary anthocyanidins, leucoanthocyanidins, and flavonoids. We focused our analysis on the following molecular questions: (i) differences in cyanidin catechols ( +)-catechin, leucocyanidin, and quercetin; (ii) the loss of hydroxyl presents in the R1 radical of leucoanthocyanidin in the functional groups linked to C4 (ring C); and (iii) the electron affinity of the 3-hydroxyl group (R7) in the flavonoids delphinidin, pelargonidin, cyanidin, quercetin, and kaempferol. We show unprecedented results for bond critical point (BCP) of leucopelargonidin and leucodelphirinidin. The BCP formed between hydroxyl hydrogen (R2) and ketone oxygen (R1) of kaempferol has the same degrees of covalence of quercetin. Kaempferol and quercetin exhibited localized electron densities between hydroxyl hydrogen (R2) and ketone oxygen (R1). Global molecular descriptors showed quercetin and leucocyanidin are the most reactive flavonoids in electrophilic reactions. Complementary, anthocyanidins are the most reactive in nucleophilic reactions, while the smallest gap occurs in delphinidin. Local descriptors indicate that anthocyanidins and flavonols are more prone to electrophilic attacks, while in leucoanthocyanidins, the most susceptible to attack are localized in the ring A. The ring C of anthocyanidins is more aromatic than the same found in flavonols and leucoanthocyanidins. METHODS: For the analysis of the molecular properties, we used the DFT to evaluate the formation of the covalent bonds and intermolecular forces. CAM-B3LYP functional with the def2TZV basis set was used for the geometry optimization. A broad analysis of quantum properties was performed using the assessment of the molecular electrostatic potential surface, electron localization function, Fukui functions, descriptors constructed from frontier orbitals, and nucleus independent chemical shift.

CONTEXT: Hydrogen bonds (HB) influence the conformational preferences of biomolecules and their optical and electronic properties. The directional interaction of molecules of water can be a prototype to understand the effects of HBs on biomolecules. Among the neurotransmitters (NT), L-aspartic acid (ASP) stands out due to its importance in health and as a precursor of several biomolecules. As it presents different functional groups and readily forms inter- and intramolecular HBs, ASP can be considered a prototype for understanding the behavior of NTs when interacting by HB with other substances. Although several theoretical studies have been performed in the past on isolated ASP and its formed complexes with water, both in gas and liquid phases, using DFT and TD-DFT formalisms, these works did not perform large basis set calculations or study electronic transitions of ASP-water complexes. We investigated the HB interactions in complexes of ASP and water molecules. The results show that the interactions between the carboxylic groups of ASP with water molecules, forming cyclic structures with two HBs, lead to more stable and less polar complexes than other conformers formed between water and the NH2 group. It was observed that there is a relationship between the deviation in the UV-Vis absorption band of the ASP and the interactions of water with the HOMO and LUMO orbitals with the stabilization/destabilization of the S1 state to the S0 of the complexes. However, in some cases, such as 1:1 complex ASP-W2, this analysis may be inaccurate due to small changes in ΔE. METHODS: We studied the landscapes of the ground state surface of different conformers of isolated L-ASP and the L-ASP-(H2O)n complexes (n = 1 and 2) using the DFT formalism, with the B3LYP functional, and six different basis sets: 6-31 +  + G(d,p), 6-311 +  + G(d,p), D95 +  + (d,p), D95V +  + (d,p), cc-pVDZ, and, cc-pVTZ basis sets. The cc-pVTZ basis set provides the minimum energy of all conformers, and therefore, we performed the analysis with this basis set. We evaluated the stabilization of the ASP and complexes using the minimum ground state energy, corrected by the zero point energy and the interaction energy between the ASP and the water molecules. We also calculated the vertical electronic transitions S1 ← S0, and their properties using the TD-DFT formalism at B3LYP/cc-pVTZ level with the optimized geometries for S0 state with the same basis set. For the analysis of the vertical transitions of isolated ASP and the ASP-(H2O)n complexes, we calculated the electrostatic energy in the S0 and S1 states. We performed the calculations with the Gaussian 09 software package. We used the VMD software package to visualize the geometries and shapes of the molecule and complexes.

CONTEXT: By means of ab initio molecular dynamics simulations, possible boron-rich amorphous silicon borides (BnSi1-n, 0.5 ≤ n ≤ 0.95) are generated and their microstructure, electrical properties and mechanical characters are scrutinized in details. As expected, the mean coordination number of each species increases progressively and more closed packed structures form with increasing B concentration. In all amorphous models, pentagonal pyramid-like configurations are observed and some of which lead to the development of B12 and B11Si icosahedrons. It should be noted that the B11Si icosahedron does not form in any crystalline silicon borides. Due to the affinity of B atoms to form cage-like clusters, phase separations (Si:B) are perceived in the most models. All simulated amorphous configurations are a semiconducting material on the basis of GGA+U calculations. The bulk modulus of the computer-generated amorphous compounds is in the range of 90 GPa to 182 GPa. As predictable, the Vickers hardness increases with increasing B content and reaches values of 25-33 GPa at 95% B concentration. Due to their electrical and mechanical properties, these materials might offer some practical applications in semiconductor technologies. METHOD: The density functional theory (DFT) based ab initio molecular dynamics (AIMD) simulations were used to generate B-rich amorphous configurations.

CONTEXT: The Maillard reaction is a high-temperature reaction of amino acids and carbohydrates to produce macromolecular substances such as melanoidins and intermediate reducing ketones, aldehydes, and volatile compounds. At present, only very limited researches involved the reaction mechanisms of Maillard reaction, which causes a lot of confusion in understanding numerous food processes. The detailed calculations of Maillard reaction are urgently needed. METHODS: The density functional theory (DFT) method (M06-2X/6-311G*) was used to deeply explore the specific mechanism of the primary and intermediate stages of Maillard reaction for a selected model system. RESULTS: The results show that the basic reaction processes in primary stage are the formation of Schiff-base by the condensation of amino and carbonyl groups, and then, Schiff-base tautomerization twice through proton transfer to generate Amadori rearrangement products. In the intermediate stage, two main reaction paths, 1-2 and 2-3 enolization, were comprehensively investigated. The first route finally generates 5-hydroxymethylfurfural through isomerization, dehydration, hydrolysis, elimination, and condensation, and the second route products dicarbonyl compounds through isomerization and elimination and then Strecker degradation forms aldehydes through condensation, decarboxylation, hydrolysis, and elimination. The results show that both paths are involved in complex reactions, some are lower barrier reactions, and some higher barrier reactions. An important aspect is that water catalysis is critical in all of these reactions; it is present in most processes. Our study deepens the understanding of the Maillard reaction from molecular level and facilitate the regulation of some harmful products.

CONTEXT: Previous theoretical studies have suggested that two-dimensional (2D) MBene materials might display adequate monatomic catalytic activity for the hydrogen evolution reaction (HER). Recently, a study reported the experimental synthesis of a 2D MBene (Mo4/3B2), re-defined as boridene, albeit no effort has been devoted to explore the single-atom catalytic activity for HER of this experimentally synthesized 2D material. Therefore, we herein investigate the single-atom HER performance of the boridene. Interestingly, with Mo defects mixed with single Au and Zn atoms shows excellent hydrogen evolution performance, and the change in the Gibbs free energy ([Formula: see text]) value is close to 0 eV, which can even match the performance of Pt-based materials. Through analysis of the charge density difference and density of states, the mechanism affecting the HER performance is explained at the electronic level. This work provides a new direction for the use of the Mo4/3B2 monolayer two-dimensional materials in the field of single-atom catalysis for HER. METHODS: This study used the DFT calculations in Vienna ab initio simulation package. The GGA-Perdew-Burke-Ernzerhof functional with DFT-D2 correction is used to describe the exchange-correlation interactions. The projection augmented wave is used with the plane wave cutoff of 500 eV. The convergences of energy and force are 10-5 eV and 0.01 eV/Å, respectively. A vacuum layer with a height of 20 Å is set in the Z direction. For geometry optimization, self-consistent, and DOS calculations, the k-point grids sampled in Brillouin zones are 3 × 3 × 1, 9 × 9 × 1, and 9 × 9 × 1, respectively. The AIMD simulation is performed in the canonical ensemble (NVT), and the temperature was maintained at 300 K by Nosé-Hoover thermostats with a time step of 2.0 fs.

BACKGROUND: In the present work, DFT and time-dependent DFT calculations were performed to investigate the role of anchoring groups on the photophysical properties and reveal structure-property correlations of triphenylamine (TPA) derivatives. The selected anchoring groups are tetrazole, acrylamide, hydantoin, and rhodanine. RESULTS: Our results show that the different anchoring groups employed alter the planarity, intramolecular charge transfer properties, and HOMO-LUMO gap and hence influence the optoelectronic properties of the dyes. Although all molecules fulfill the basic requirements with suitable energy levels, band gap, absorption, and charge transfer properties, the dye with rhodanine acceptor (TPA4) was the most promising candidate due to its lowest HOMO-LUMO gap, red-shifted highest λmax absorption value, better ICT pattern, low total reorganization energy, and good electron injection properties. Overall, it is anticipated that the results of this investigation will point to new avenues for the experimental fabrication of remarkably effective metal-free organic dyes for solar cell applications.