Journal of Molecular Modeling最新文献

Context

Among two-dimensional (2D) materials, transition metal dichalcogenides (TMDs) stand out for their remarkable electronic, optical, and chemical properties. Their atomic thinness also imparts flexibility, making them ideal for flexible and wearable devices. However, our understanding of the mechanical characteristics of molybdenum ditelluride (MoTe₂), particularly with defects such as pits, remains limited. Such defects, common in grown TMDs, degrade the mechanical properties and affect electronic and magnetic behaviors. This study uses molecular dynamics (MD) simulations of uniaxial and biaxial tensile loading performed on monolayer molybdenum ditelluride sheets of 2H phase containing triangular pits of varying vertex angles to investigate their fracture properties and visualize their crack propagation. From the stress–strain relationship, Young’s modulus, fracture strain, ultimate tensile strength, and toughness for comparative analysis were calculated.

Method

Tensile loading simulations were performed in molecular dynamics (MD) software LAMMPS, using the Stillinger–Weber (SW) interatomic potential, under strain rate 10⁸ s⁻¹ at room temperature (300 K). From the stress–strain relationship obtained, we calculated Young’s modulus, fracture strain, ultimate tensile strength, and toughness. Results showed that variations in pit edge length, angle, and perimeter significantly affected these properties in monolayer MoTe₂. Regulated alteration of pit angle under constant simulation conditions resulted in improved uniaxial mechanical properties, while altering pit perimeters improved biaxial mechanical properties. Stress distribution was visualized using OVITO software. MoTe₂ with pit defects was found to be more brittle than its pristine counterpart. This study provides foundational knowledge for advanced design strategies involving strain engineering in MoTe₂ and similar TMDs.

Context

High-pressure chemistry has advantages in exploring novel energetic materials and is the key to the development of new high-energy materials. The complexity and danger of experimental processes require a deeper understanding by advanced simulation techniques. Therefore, a high-precision comparative DFT-D study was performed to investigate the effect of pressure on series of catenated nitrogen energetic crystals. The results show that there exist phase transitions for N₄, N₈, and N₁₀ at 4 GPa, 3 GPa, and 2 GPa respectively, which are embodied in various properties of these crystals. Studies on band gap and DOS indicate pressure-induced improvement on the ability for electrons transition from occupied orbitals to empty ones. Hirshfeld surface analysis qualitatively suggests that hydrogen bonding interactions are becoming dominant inter-molecular interactions. The topological analysis quantitatively reveals that pressure is beneficial to enhancing the inter-molecular hydrogen bonding energy, thereby playing an important role in the stability of high-pressure phases. The discussions on mechanical properties imply that pressure can improve the rigidity of these energetic systems and enhance their mechanical properties. Our findings evidence the high-pressure phase transitions for catenated nitrogen energetic crystals, which lay the theoretical foundation for the development of novel energetic materials.

Methods

Series of catenated nitrogen energetic crystals N₄, N₈ and N₁₀ were obtained from experiments. Optimizations were performed by GGA/PBE functional and G06 dispersion correction within the framework of CASTEP code, and the cutoff energies of the plane waves were set to 700 eV. The particular moiety in the crystals was extracted by Multiwfn 3.6 and subsequent analysis was conducted by Gaussian 09W package.

Context

Alpha-glucosidase enzyme is considered an important therapeutic target for controlling hyperglycemia associated with type 2 diabetes. Novel scaffolds identified as potential alpha-glucosidase inhibitors from the Maybridge library utilizing pharmacophore modeling, molecular docking and biological evaluation are reported in this manuscript.

Method

A total of 51 xanthone series scaffolds previously reported as alpha-glucosidase inhibitors were collected and used as training and test sets. These sets were employed to develop and validate a pharmacophore-based 3D-QSAR model with statistically meaningful results using Schrodinger software. The model showed a high F value (F, 80.1) at five component partial least square factors, a high cross-validation coefficient (Q², 0.66) and a good correlation coefficient (R², 0.95). Pearson correlation coefficient (r) of 0.8400 indicated a greater degree of confidence in the model. Subsequently, virtual screening was performed with PHASE module of Schrodinger software using the above model to identify novel alpha-glucosidase inhibitors, and mapped compounds were evaluated for their interactions with the protein. The X-ray co-crystallised structure of the alpha-glucosidase protein in complex with acarbose (PDB Code: 5NN8) was used for molecular docking analysis using GLIDE module and a total of eight compounds were further selected for biological evaluation. Molecular dynamics analysis using GROMACS software was performed in the active site of alpha-glucosidase protein to gain insights into binding mechanism of the four active compounds which were finally found to exhibit inhibitory activity in the biological assay.

Context

In this work, we propose a computational protocol enabling the simulation of mechanochromic responses in dye-dispersed polymer blends. The main objective is the modeling of the molecular-level structural changes responsible for the modulation of the photophysical properties that lead to the mechanochromic phenomenon. In this demonstrative study, we focus on predicting the changes in optical absorption displayed by a model system consisting of a dimer of a tetraphenylethylene derivative dispersed in a polyethylene matrix. The blend is subjected to an external stimulus that causes a modulation of the polymer matrix density that translates, in turn, into the emergence of specific mechanical constraints on the optically active dimers. The accurate description of this phenomenon requires the reliable sampling of the dimer configurations induced by the interaction with the matrix under stress. These molecular geometries are associated with modified electronic structures that confer novel absorption responses to the dispersed dyes.

Methods

In the present contribution, the sampling of these structures is achieved through classical molecular dynamics (MD) simulations including a model element to apply an anisotropic mechanical force. This element allows the microscopic modeling of the chains’ and dyes’ structural rearrangements under stress. After the sampling, we compare the results of two approaches for the prediction of the optical response: (i) the calculation of a mean response from a statistical average over quantum chemical calculations on the sampled MD structures and (ii) a prediction via a more expensive hybrid scheme allowing the relaxation of the sampled molecular geometries in the presence of the matrix constraints.

Context

The dyes in the second near-infrared (NIR-II) region play a crucial role in advancing imaging technology. However, developing small-molecule dyes in NIR-II poses a significant bottleneck to meet the substantial demands in biological fields, which may be attributed to the lack of a rational design strategy. Herein, we designed a series of rhodamine analogs with more red-shifted emission by replacing the oxygen-bridge atom in xanthene-based dyes with –C(CH₃)₂, –Si(CH₃)₂, –SO₂, and –P(O)Ph. We investigated the frontier molecular orbital, electrostatic potential surfaces, the interaction region indicator, electron–hole distribution, and absorption and emission spectrum of xanthene-based dyes using (time-dependent) density functional theory. Our results demonstrated that these designed small molecular dyes exhibit long emission wavelengths covering 1377–1809 nm. We expected these findings to enable the targeted design of long-wavelength rhodamines.

Method

Geometry optimization of dyes in the ground and excited states was carried out at ω-B97XD/Def2SVP level using Gaussian 16 A03. The absorption and emission wavelengths were evaluated using 13 functional, including TPSSH, O3LYP, B3LYP*, B3LYP, PBE0, MPW1B95, PBE-1/3, PBE38, MPWB1K, MN15, BHandHLYP, ω-B97XD, and CAM-B3LYP.

Context

The heavy metal ions are the typical carcinogenic agents. Up to now, the interaction mechanism of toxic metal ions with the biomolecules such as carbohyrate have not been elucidated and reported in the detail. In this research work, the adjacent dissociation Gibbs energy (E_AB) of M³⁺(H₂O)₅(R-OH) complexes depended significantly on the molecular volume of primary alcohols and the inductive effects of substituent R in primary alcohols (R = CH₃, CH₃CH₂, CH₃CH₂CH₂, CH₃CH₂CH₂CH₂, Cl-CH₂, F-CH₂) as well as the length of linear cellulose. The affinity of M³⁺(H₂O)₅ ions with the sixth water molecule in gas phase reduced in the order as follows: Fe³⁺  > Ru³⁺  > Os³⁺, which were determined by the E_AB values and bond lengths of M–O. The water solvent made the E_AB values of Fe³⁺(H₂O)₆ ions and Fe³⁺(H₂O)₅(CH₃OH) ions changed completely in the case of the polarizable continuum model, while the Onsager model gave the good agreement with the gas phase model.

Methods

The nature of interaction between hydrated Fe³⁺(H₂O)₅ ion and the hydroxy groups of primary alcohols were investigated using density functional theory method at the B3LYP/6–311 + G** level, the PBEPBE/6–311 + G** level. The influence of water solvent was evaluated using the Onsager model and the polarizable continuum model. The two-layer ONIOM approach and the local softness analysis were employed for the hydroxy groups of linear cellulose at the B3LYP/6–311 + G**:HF/6-31G* level. The affinity of M³⁺(H₂O)₅ ions (M = Fe, Ru, and Os) with the sixth water molecule were probed at the B3LYP/QZVPP/6–311 + G** level (QZVPP basis set for the metal atoms).

Context

In researching energetic materials with high energy density, it is an effective method to introduce explosophoric groups. In this study, four series of energetic compounds were designed by functionalizing with C- or N-, introducing energetic groups -CH(NO₂)₂, -CF(NO₂)₂, -C(NO₂)₂(NF₂), -C(NO₂)₃, and-CH(NF₂)₂ into imidazole and pyrazole structures. Density functional theory was employed to optimize the structure of the target compound and subsequently to predict and evaluate its performance based on this. Meanwhile, the sensitivity of the compounds was predicted based on their electrostatic potential analysis. Following analysis of the geometric structure, detonation performance, and sensitivity of the compounds, three factors were discussed: energetic groups, functionalization methods, and skeleton structure differences. The results indicate that C-functionalization has advantages only in density, but N-functionalization is better in thermal stability, heat of formation, and sensitivity. Meanwhile, the data shows that imidazole-based compounds exhibited greater density and detonation performance in the target compounds designed within this study, while pyrazoles have a higher heat of formation and chemical stability. By analyzing the design strategy of C- or N-functionalization of novel high-energy groups on energetic imidazole or pyrazole rings and selecting a more suitable molecular construction strategy, this study provides a theoretical approach for the development of new energetic materials with excellent performance.

Method

Gaussian 09 and Multiwfn 3.8 packages are the software used for calculation, and the electrostatic potentials were depicted using the VMD program. In this study, the imidazole and pyrazole derivatives were optimized at the B3PW91/6-311G (d, p) level to acquire the relevant data for the compounds.

Context

Glioblastoma (GBM), well known as grade 4 tumors due to its progressive malignant features such as vascular proliferation and necrosis, is the most aggressive form of primary brain tumor found in adults. Mutations and amplifications in the vascular endothelial growth factor receptor (VEGFR) contribute to almost 25% of GBM tumors. And thus, VEGFR has been declared the primary target in glioblastoma therapeutic strategies. However, many studies have been previously reported that include GBM as global therapeutics challenge, but they lack the molecular level insights that could help in understanding the biological function of a therapeutically important protein playing a major role in the disease and design the best strategies to develop the potential drugs.

Methods

Therefore, to the best of our knowledge, the present study is the first time of kind, which involves multi-in silico approaches to predict the inhibition potential of withanolides from Withania coagulan against VEGFR. The study is actually based on determining the mode of action of five isolates: withanolide J, withaperuvin, 27-hydroxywithanolide I, coagule E, and coagule E, along with their respective binding energies. Molecular docking simulations revealed primarily four ligands, withanolide J (− 7.33 kJ/mol), 27-withanolide (− 7.01 kJ/mol), ajugine, withaperuvin (− 6.89 kJ/mol), and ajugine E (− 6.39 kJ/mol), to have significant binding potencies against the protein. Ligand binding was found to enhance the confirmational stability of the protein revealed through RMSD analysis, and RMSF assessment revealed the protein residues especially from 900–1000 surrounding the binding of the protein. Structural and dynamics of the protein via dynamics cross-correlation movement (DCCM) and principal component analysis (PCA) in both the unbound form and complexed with most potent ligand, withanolide J, reveal the ligand binding affecting the entire conformational integrity of the protein stabilized by hydrogen bonds and electrostatic attractions. Free energy of binding estimations by means of molecular mechanics Poisson-Boltzmann surface area (MMPBSA) method further revealed the withanolide J to have maximum binding potency of the all ligands. Withanolide J in final was also found to have suitable molecular characterizations to cross the blood–brain barrier (BBB +) and reasonable human intestinal absorption ability determined by ADMET profiling via admetSAR tools.

Graphical abstract

Context

Phosphodiester bonds, which form the backbone of DNA, are highly stable in the absence of catalysts. This stability is crucial for maintaining the integrity of genetic information. However, when exposed to catalytic agents, these bonds become susceptible to cleavage. In this study, we investigated the role of different metal dications (Ca²⁺, Mg²⁺, Zn²⁺, Mn²⁺, and Cu²⁺) in promoting the hydrolysis of phosphodiester bonds. A minimal DNA model was constructed using two pyrimidine nucleobases (cytosine and thymine), two deoxyribose units, one phosphate group, and one metallic dication coordinated by six water molecules. The results highlight that Cu²⁺ is the most efficient in lowering the energy barrier for bond cleavage, with an energy barrier of 183 kJ/mol, compared to higher barriers for metals like Zn²⁺ (202 kJ/mol), Mn²⁺ (202 kJ/mol), Mg²⁺ (210 kJ/mol), and Ca²⁺ (223 kJ/mol). Understanding the interaction between these metal ions and phosphodiester bonds offers insight into DNA stability and organic data storage systems.

Methods

DFT calculations were employed using Gaussian 16 software, applying the B3LYP hybrid functional with def2-SVP basis sets and GD3BJ dispersion corrections. Full geometry optimizations were performed for the initial and transition states, followed by identifying energy barriers associated with phosphodiester bond cleavage. The optimization criteria included maximum force, root-mean-square force, displacement, and energy convergence thresholds.

Context

Nitrenium ions are intermediates in the metabolic routes producing the highly carcinogenic nitrosamines and binding to DNA molecules. The reaction mechanism of nitrenium molecules with explicit water molecules is sensibly dependent on the number of waters: when a second molecule is involved, it acts as a catalyst for the reaction, lowering intrinsic activation barriers regardless of the substituent. For all cases, the reaction force constants and reaction electron flux indicate highly synchronous reactions for ({n=1}). Conversely, for ({n=2}) highly non-synchronous reactions are obtained, involving two separate proton transfers happening early and late in the reaction path. As a test case, for the simplest ([text {N}text {H}_{2}]^{+} + 2 text {H}_{2}text {O}) reactions, orbital interactions within the NBO paradigm, bond orders, and their derivatives indicate that each individual proton transfer is highly synchronous.

Methods

Molecular geometries were optimized and characterized at the B3LYP/6–311++G(d, p) level. Intrinsic reaction coordinates were calculated. CCSD(T) single point energies with the same basis were computed on all stationary points. The reaction force, reaction force constant, and reaction electron flux are used to study the evolution of the reacting systems. Natural bond orbitals are used to understand the primitive changes driving the reaction.