Journal of Molecular Modeling最新文献

Context

AlSi10Mg alloy is among the most widely recognised aluminium alloys due to its dimensional stability and exceptional properties for additive manufacturing. However, the alloy’s performance can be improved and optimized through appropriate reinforcement and control of the manufacturing process parameters. This work focuses on the impact of process parameters (laser power, scan speed and layer thickness) and graphene reinforcement on the mechanical properties of SLM-fabricated AlSi10Mg alloy. The results indicate that, increasing the laser power within the studied range enhances both tensile and compressive strength. Furthermore, reducing the laser scanning speed improved these properties, although further reduction beyond a threshold value minimizes the impact. However, increasing the layer thickness while maintaining the same laser power reduces the material properties, the effect can be mitigated by supplying more laser energy. The addition of graphene as reinforcement has markedly improved the composite properties, improving its elastic and plastic behaviour. The graphene reinforcement also improved the stiffness, yield strength, toughness, and ultimate strength making it a highly effective way to enhance the AlSi10Mg alloy performance.

Methods

In this study, molecular dynamics (MD) was performed to model the selective laser melting (SLM) process using LAMMPS (large-scale atomic/molecular massively parallel simulator) software. The simulation setup was programmed to analyse the impact of process parameters, including laser power (500, 600, and 700 μW), scanning speed (1, 1.5, and 2 nm/ps) and layer thickness (two and three-particle layer system) on the mechanical properties (tensile and compressive strength) of AlSi10Mg alloy. Additionally, the impact of graphene reinforcement was also examined using nano-scale simulation. The simulation provides insights into both the SLM process and the mechanical behaviour of the alloy and its composite under different processing conditions.

Context

Natural fluorescence in biochemical structures can result in unsatisfactory outcomes in cell imaging. This drawback can be addressed by using probe molecules that fluoresce via Excited State Intramolecular Proton Transfer (ESIPT), thereby improving resolution and the signal-to-noise ratio. A docking study was conducted to estimate the binding free energy of 132 benzazoles and to determine their binding modes (minor groove (MG) or intercalation (INT)) to DNA, comparing them with the commercial probes 4’,6-Diamidino-2-phenylindole dihydrochloride (DAPI) and acridine orange (AO). Atomistic molecular dynamics simulations under physiological conditions were performed for the five top-ranked ligands, as well as for AO and DAPI. Three of the investigated ligands exhibited stronger binding energy than both commercial probes, while the other two showed stronger binding energy than AO, but not than DAPI. The proposed benzazoles acted as intercalators and MG binders. Using molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) calculations to estimate the binding free energy of the ligand-receptor complexes, we could confirm the strong interaction of these molecules with DNA. Quantum Chemical Calculations were performed to estimate the emission energies upon excitation of the selected ligands, which showed large Stokes shift values and, for some molecules, favorable ESIPT processes. Benzazoles 1–5 demonstrated strong interactions with DNA, surpassing the commercial probes in binding strength and displaying promising photophysical properties. Consequently, these ligands are promising fluorescent DNA probes, suitable for various diagnostic techniques.

Methods

132 Benzazole ligands were constructed and optimized using Gabedit and docked to a B-DNA oligomer using AutoDock. Molecular dynamics simulations were run in GROMACS, using AMBER-parmbsc0 and GAFF force fields. Quantum chemical calculations (TD-DFT) in Gaussian 16 provided excited-state properties, optimized at the CAM-B3LYP/cc-pVDZ level of theory.

Context

Based on the periodic density functional theory, we systematically studied 13 kinds of anhydrous pentazole non-metallic ionic salts synthesized by other scientists (PA-1 ~ PA-13)[Chem-An Asian J, 13(8):924-928 6, J Am Chem Soc 140(48):16488-16494 7, J Mater Chem A 7(20):12468-12479 8, Chem-An Asian J 14(16):2877-2882 9]. The results show the following: first, the heat of formation of PA-1 ~ PA-13 exceeds that of TNT and RDX. The heat of formation of PA-9 reaches 1357.56 kJ/mol, and it has excellent detonation performance (D = 9.41 km/s, P = 34.79 GPa, Q = 7.78 kJ/g), demonstrating the potential of high-energy ionic salts. Second, in cations, the introduction of -NH₂ or -OH substituents is beneficial to improving the heat of formation and detonation performance, while the introduction of -COOH substituents is unfavorable for the improvement of the heat of formation and detonation performance. Third, replacing -NH₂ with -OH can improve the chemical reactivity of pentazole ionic salts, while increasing the number of -NH₂ or introducing carbonyl groups will reduce the reactivity. Forth, the introduction of -NH₂ can enhance the hydrogen bonding and increase the electron density of pentazole ionic salts, and the introduction of -COOH can enhance the van der Waals interaction and the steric hindrance effect. Fifth, with other conditions remaining unchanged, the larger the volume of the cation, the greater the impact sensitivity and friction sensitivity of the ionic salt as actually measured, and the more stable the ionic salt is.

Method

All calculations in this paper are performed using Gaussian 16 based on density functional theory. Firstly, the structures of the derivatives were optimized at the level of B3LYP-D3/6-311G**, and then single-site energy calculations were carried out at the level of M06-2X-D3/def2-TZVPP, in order to explore the influence of different cation structures on various properties of pentazole ionic salts.

Context

Pentazole ion salt is a cutting-edge new type of all-nitrogen ion high-energy material. When subjected to an external electric field (EEF), the structure and various properties of pentazole ion salts are altered. This article studied six types of pentazole ion salts (PA-1 ~ PA-6) under an external electric field (intensity 0 ~ 0.008 a.u.). GGA/PBE method was used to calculate and analyze the lattice constants, cell volume, density, bond length, bond angle, dihedral angle, energy bands, and density of states of pentazole ion salts. The results showed that six types of pentazole ion salts exhibited good crystal and geometric stability under the action of an external electric field. The band gap exhibits different levels of decrease, and electrons are more prone to transition, resulting in a continuous weakening of the stability of pentazole ion salts. The dense attitudes of PA-1, PA-3, PA-4, and PA-6 gradually shift towards the low-energy region, with an increase in peak width and a splitting phenomenon. The peak values show a gradually decreasing trend. The electronic structures of PA-2 and PA-5 exhibit high stability. PA-3 and PA-6 are more sensitive to the applied electric field.

Methods

The Materials Studio software has been chosen for simulation and computation in this study. The GGA/PBE method has been utilized for the calculation and simulation of external electric fields, with the strength ranging from 0 to 0.008 a.u. and an increment gradient of 0.001 a.u.

Context

This study utilizes molecular dynamics (MD) simulation to investigate polycrystalline dual-phase titanium (DP Ti) deformation behavior and phase transformation under tensile and compressive loading. The analysis focuses on the influence of hexagonal close-packed (HCP) phase fraction, strain rate, and temperature on the mechanical properties and microstructural evolution. The results indicate that increasing the HCP phase fraction enhances the elastic modulus (36.5%), yield strength, and strain hardening while maintaining acceptable ductility. The optimal mechanical performance is achieved at 75.4% HCP phase fraction. Strain rate has significantly influenced mechanical response, with higher rates promoting increased yield strength, elastic modulus, dislocation activity, and phase transformations to body-centered cubic (BCC) and amorphous phases. In contrast, raising the temperature from 300 to 900 K results in thermal softening, reduced strength, and diminished dislocation activity, alongside pronounced HCP-to-BCC phase transformation. Interphase boundaries are critical in shaping the deformation mechanisms, influencing dislocation evolution and strain hardening. During deformation, Shockley, Hirth, and other partial dislocations appear. These findings offer valuable insights into the deformation mechanisms and phase behavior of DP Ti, emphasizing its potential for applications requiring a balance between strength and ductility.

Methods

The simulations utilized the open-source software LAMMPS (Large-scale Atomic/Molecular Massively Parallel Simulator) for modeling atomic-scale interactions. Visualization of the evolving atomic structures was performed using OVITO (Open Visualization Tool). To analyze microstructural changes, the Dislocation Extraction Algorithm (DXA) and Common Neighbor Analysis (CNA) methods were employed.

Context

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease characterized by very limited treatment options and significant side effects from existing therapies, highlighting the urgent need for more effective drug-like molecules. Transforming growth factor-beta receptor 1 (TGF-βR1) is a key player in the pathogenesis of IPF and represents a critical target for therapeutic intervention. In this study, the potential of plant-derived flavonoid and coumarin compounds as novel TGF-βR1 inhibitors was explored. A total of 1206 flavonoid and coumarin derivatives were investigated through a series of computational approaches, including drug-like filtering, virtual screening, molecular docking, 200-ns molecular dynamics (MD) simulations in triplicate, maximum common substructure (MCS) analysis, and absorption-distribution-metabolism-excretion-toxicity (ADMET) profiling. 2′,3′,4′-trihydroxyflavone and dicoumarol emerged as promising plant-based hit candidates, exhibiting comparable docking scores, MD-based structural stability, and more negative MM/PBSA binding free energy relative to the co-crystallized inhibitor, while surpassing pirfenidone in these parameters and demonstrating superior pharmacological properties. In light of the findings from this study, 2′,3′,4′-trihydroxyflavone and dicoumarol could be considered novel TGF-βR1 inhibitors for IPF treatment, and it is recommended that their structural optimization be pursued through in vitro binding assays and in vivo animal studies.

Methods

The initial dataset of 1206 flavonoid and coumarin derivatives was filtered for drug-likeness using Lipinski’s Rule of Five in the ChemMaster—Pro 1.2 program, resulting in 161 potential candidates. These compounds were then subjected to virtual screening against the TGF-βR1 kinase domain (PDB ID: 6B8Y) using AutoDock Vina 1.2.5, identifying the top three hit compounds—dicoumarol, 2′,3′,4′-trihydroxyflavone, and 2′,3′-dihydroxyflavone. These hits underwent further exhaustive molecular docking for refinement of docking poses, followed by 200-ns MD simulations in triplicate using the AMBER03 force field in GROMACS. Subsequently, the binding free energies were calculated using the Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) method. MCS analysis was conducted to determine shared structural features among the top three hits, while ADMET properties were predicted using Deep-PK, a deep learning-based platform. Finally, the ligand–protein interactions were further visualized, analyzed, and rendered using ChimeraX, Discovery Studio Visualizer, and Visual Molecular Dynamics (VMD) program.

Context

The formation of hot spots and chemical decomposition of explosives under shock loading are crucial for understanding the initiation of heterogeneous explosives. In this study, molecular dynamics simulations were employed to investigate the collapse of nanovoids, hotspot formation, and decomposition reactions of HMX under four typical stress wave loadings: long-pulse, short-pulse, triangular wave, and ramp wave. Different loading modes lead to varying critical transition velocities at which void collapse shifts from uniform to jetting collapse. For long-pulse loading, short-pulse and ramp wave loadings, and triangular wave loading were about 1.75 km/s, 2.25 km/s, 2 km/s and 2.5 km/s, respectively. Furthermore, it was found that under the uniform collapse mode, the hot spot temperature remains below 2000 K, and the initial decomposition pathway of HMX primarily involved the breaking of the N–NO₂ bond. In the jetting collapse mode, hydrogen transfer and the formation of HONO were observed. These findings contribute to a better understanding of the relationship between shock loading modes and void collapse patterns in explosives, revealing the initial reaction pathways of HMX under different collapse modes, and providing theoretical guidance for experimental investigations, to provide a theoretical basis for developing a new ignition model.

Methods

Based on the ReaxFF-MD method, Lammps software was used to simulate the shock process of the HMX system with circular holes, and the reaction force field files containing C, H, O, and N elements were used. The post-processing of the results was implemented using OVITO and self-programmed Python scripts.

Context

The mercury ion Hg²⁺, and its derivatives, organomercurials are high toxicity to humans due their ability to bioaccumulate. In view of these problems, studies of the interaction of these potentially toxic compounds with matrices allow verify if they can be detected, or help determine their adsorptive capacity. In this context, the work aims to theoretically evaluate the interaction between the B₃O₃ matrix and the potentially toxic compounds Hg²⁺, CH₃Hg⁺, CH₃CH₂Hg⁺, and C₆H₅Hg⁺. The binding energy values showed that the interaction occurs effectively; being spontaneous and exothermic for all the interactions evaluated. The structural properties demonstrate that mercury interacts with the oxygen atoms of the B₃O₃ matrix, with bond lengths ranging from 2.365 to 3.777 Å and that all organomercurials form hydrogen bonds. The topological parameters of quantum theory of atoms in molecules (QTAIM) categorized the nature of the interactions in electrostatic for Hg^…O. The non-covalent interaction analyses presented a bluish color, between Hg and matrix oxygen indicating a strong attraction interaction and Van der Waals interactions ( green color) for the interaction of the organic group and B₃O₃. Thus, it can be confirmed that the study showed that the B₃O₃ matrix is efficient for the interactions, enabling future experimental studies of the application of this matrix in adsorptive processes or for molecular filters.

Methods

All calculations of density functional theory were performed using the program Gaussian 16 and the structures of B₃O₃ matrix, Hg²⁺, CH₃Hg⁺, CH₃CH₂Hg⁺, and C₆H₅Hg⁺ were generated using the GaussView program. The optimization and vibrational frequency calculations were performed using the functional ωB97XD and 6-31G(d,p) basis set for the H, B, C, and O atoms, while for the Hg atom the basis set used was CEP-31G with compact effective pseudopotential. All analyses were conducted at this level of theory. The quantum theory of atoms in molecules analysis were performed using AIMALL software. Non-covalent interaction calculations were carried out using Multiwfn software, and the structures were visualized using the visual molecular dynamics program.

Metal alloys are engineered materials designed to enhance mechanical performance. Achieving optimal mechanical properties through alloy composition has been the focus of extensive research. This study employs the meshless molecular dynamics method to investigate the influence of temperature, strain rate, and copper content on the mechanical properties of Aluminum/Copper (Al-Cu) superalloy. The research focuses on the variation of copper content from 1 to 20%, temperature from 300 to 600 K, and strain rates between 0.001 ps⁻¹ and 0.01 ps⁻¹, assessing their impact on the ultimate tensile strength (UTS) and elastic modulus of the alloy. The results show a significant enhancement in both UTS and elastic modulus with increasing copper content, with the UTS increasing by 359% and the elastic modulus by 281% when copper content rises from 1 to 20%. In contrast, increasing the temperature from 300 to 600 K results in a 31% reduction in UTS and an 18.9% decrease in elastic modulus, highlighting the sensitivity of these properties to thermal effects. Additionally, higher strain rates were found to improve both UTS and elastic modulus, with an 11.95% increase in UTS and an 8.34% increase in elastic modulus at the highest strain rate (0.01 ps⁻¹). These findings demonstrate the critical role of alloy composition, temperature, and strain rate in tailoring the mechanical properties of Al-Cu alloys, providing insights for optimizing the material for high-performance applications.

Context

Non-alcoholic fatty liver disease (NAFLD) has become a significant health concern. Existing farnesoid X receptor (FXR) agonists like GW4064 and LYS2562175 show poor pharmacokinetics, prompting researchers to develop alternative molecules. This study aims to pinpoint the structural features responsible for exhibiting FXR agonism of a series of hybrid structures of GW4064 and LYS2562175 with improved pharmacokinetic properties which supersede the existing parent ligands. Electronegative components were found to critically influence biological activity on the molecular level, supported by 2D- and 3D-Quantitative Structure Activity Relationship (2D- and 3D-QSAR) analyses. Quantitative Activity-Activity Relationship (QAAR) highlighted key descriptors impacting cellular level FXR binding potential. Molecular dynamics (MD) simulations identified pivotal interactions, such as π-π and H-bond interactions with key residues. Furthermore, binding free energy calculated with Molecular Mechanics with Generalised Born and Surface Area solvation (MM-GBSA) analyses with selected compounds reflected the variations in their binding potential towards FXR protein.

Methods

The study began by curating ligand SMILES and preparing a dataset with molecular and cellular activity as dependent variables. AlvaDesc descriptors and interpretable descriptors were calculated using the OCHEM webserver. QSAR analyses were performed using Sequential Forward Selection (SFS) and Genetic Algorithm (GA) methods, while QAAR analysis used 50% effective concentration at the molecular level as an independent variable with the same algorithms. 3D QSAR analysis was performed with the Open3DQSAR tool. Docking studies in AutoDock 4.2 with FXR protein identified optimal ligand poses, and 500 ns MD simulations were performed with Amber 20. The use of open-access tools ensures reproducibility and accessibility for future research.

Graphical Abstract