Journal of Molecular Modeling最新文献

Context

Pharmaceutical residues such as ciprofloxacin (CIP) are increasingly recognized as persistent aquatic contaminants with adverse ecological impacts. Understanding their interactions with functionalized nanomaterials is essential for designing efficient adsorbents. Here, we explore the adsorption mechanism of CIP on carboxyl-functionalized carbon nanotubes (CNT–COOH) under aqueous conditions. The study reveals favorable binding energetics, significant stabilization through solvation effects, and electronic structure changes that highlight CNT–COOH as an effective platform for pharmaceutical pollutant removal.

Methods

All calculations were carried out using density functional theory (DFT). Geometry optimizations, harmonic vibrational frequency analyses, and solvation modeling were performed within the polarizable continuum model (PCM, water). Electronic structure calculations were conducted with B3LYP, M06-2X, and ωB97X-D functionals in combination with the 6-311++G(d,p) basis set. The Gaussian 09W package was employed for all computations, and GaussView 6 was used for molecular visualization and analysis.

Context

This study investigates the interaction of synthetic coumarin benzamides (CmB1-10) obtained from the literature with the 5-HT2CR serotonergic receptor and the carbonic anhydrase II (CA-II) enzyme, with potential pharmacological applications in anxiety disorders. CmB is a type of drug that has been shown to affect the 5-HT2CR receptor. This receptor is involved in mood, thinking, and muscle control. CmB has similar effects to other known antagonists. In addition, the dimethylated derivatives (3,4-CH3 and 3,5-CH3)—CmB2 and CmB4—were more effective as enzyme inhibitors, according to the literature. Structural analyses revealed that the CmB2 and CmB4 derivatives exhibit a higher nucleophilic character due to the electron-donating properties of the dimethyl substituents. The dimethylated derivatives exhibited ideal pharmacokinetic properties, including an apparent permeability (Papp, A→B 1.1 × 10⁻⁵ cm/s) and metabolic stability. The virtual screening revealed the structural specificity of the compounds for CA-II and 5-HT2CR, with affinity energy for 5-HT2CR – 10 kcal/mol. Molecular dynamics simulations estimated a low binding free energy (ΔG) of the lead compounds to about 5-HT2CR, indicating that they were energetically more stable complexes. This research provides a basis for future experimental studies that corroborate the neuromodulatory action of CmB derivatives.

Methods

This study utilized the integration of molecular modeling techniques at quantum levels (DFT/B3LYP/6-311++G(d,p)) using the Gaussian 09 program to investigate structural/electronic properties and classical levels such as molecular docking and molecular dynamics, using the AutoDockVina™ and GROMACS® programs respectively, to investigate the interaction between meanings and biological targets (5-HT2CR and CA-II). DMPK was used to investigate the bioavailability and metabolism of the drugs from the results.

Context

Surfactant flooding represents one of the critical methods in chemical enhanced oil recovery (EOR) technology. However, under high-temperature and high-salinity conditions, the interfacial properties of surfactants are prone to alteration, leading to reduced interfacial activity. In this study, three distinct types of surfactants derived from saturated cardanol were selected: 8EO8POH (nonionic surfactant), 8EO8POC2SO₃ (sulfonate surfactant), and 8EO8POSO₃ (sulfate surfactant). A high-temperature (30 ~ 180 ℃) and high-salinity (NaCl + CaCl₂ concentration of 1.0 mol/L) system model was constructed through molecular dynamics simulations to evaluate their thermal resistance. The results indicate that an increase in temperature enhances the aggregation of water molecules and crude oil components around the surfactant molecules, thereby strengthening weak interactions. Under these conditions, the balance between hydrophilic and lipophilic effects becomes the predominant factor determining the superior interfacial performance of the surfactants. Consequently, the order of heat resistance is as follows: 8EO8POC2SO₃ > 8EO8POSO₃ > 8EO8POH.

Method

In this study, Packmol was employed to construct the model, and Gromacs was used to perform molecular dynamics simulations under the GAFF force field. The simulated pressure was set to 1115.0 kPa. The temperatures were set at 303.15 K, 333.15 K, 363.15 K, 393.15 K, 423.15 K, and 453.15 K, respectively. The time step for all simulations was set to 2 fs. In the 1 ns and 15 ns NPT simulations, the Berendsen and Parrinello-Rahman methods were employed to maintain system pressure, and the temperature control was achieved through velocity-rescale. The LINCS algorithm was utilized to constrain molecular bond lengths. Short-range and long-range were used Lennard–Jones potential and Particle-Mesh Ewald (PME) summation method.

Context

The growing demand for miniaturized and flexible electronics highlights the inherent structural and mechanical limitations of traditional inorganic materials. Conjugated organic polymers (COPs) have emerged as a promising class of materials for next-generation electronic devices, yet enhancing their electrical conductivity remains a critical objective. Herein, we report a theoretical investigation of the structural, energetic, electronic, and spectroscopic properties of pristine and doped polythiophene (PTh) and polypyrrole (PPy) oligomers. The doping process was modeled via electron removal and charge compensation by a ClO₄⁻ anion. Doping induces the formation of polaronic and bipolaronic states, which is accompanied by a substantial reduction in the HOMO–LUMO gap (E_gap). These results indicate a marked enhancement in the electrical conductivity of the polymers.

Methods

DFT and TD-DFT calculations were conducted using the PBE0 functional along with Pople’s split valence 6-31G(d,p) basis set, which includes polarization functions on all atoms.

Context

Processing techniques such as annealing or sintering, as well as high-temperature operational environments like nuclear reactor cladding, are influenced by temperature gradient conditions, which drive grain boundary migration toward the thermal gradient, thereby altering material properties. The high melting point of body-centered cubic (BCC) transition metal vanadium (~ 2194 K) enables simulations across a wide temperature gradient range without phase transformations, allowing a focused investigation of the effects of temperature gradients and grain boundary structure on migration rate. We employed molecular dynamics simulations to investigate the atomic rearrangement and migration behavior of different types of grain boundaries in vanadium metal under temperature gradient driving forces. The study revealed that the grain boundary structure significantly affects the migration rate below the disordering transition temperature (approximately 0.5–0.7 ({T}_{m})). Low-misorientation grain boundaries can be described by dislocation structures, where temperature gradients induce sliding of 1/2 < 111 > screw dislocations while < 100 > edge dislocations hardly slide or climb. Some high-misorientation grain boundaries enable coordinated atomic motion through hexagonal or square lattice structures. Above the disordering transition temperature, local disordering occurs, and excess free volume and vacancies facilitate a transition from hopping-like atomic motion to collective string-like atomic motion or atomic diffusion. Additionally, grain boundary roughening transitions promote structural disordering, significantly enhancing migration rates. These findings elucidate the temperature-dependent nature and multi-mechanism synergy of grain boundary migration in vanadium, providing a theoretical foundation for optimizing microstructure and mechanical properties.

Methods

In this study, molecular dynamics simulations were utilized to investigate the influence of grain boundary structure on migration behavior in BCC vanadium under temperature gradients. The simulations were performed using LAMMPS (Large-scale Atomic/Molecular Massively Parallel Simulator) software with an Embedded Atom Method (EAM) potential to model interatomic interactions. Bicrystal models with various grain boundary types (e.g., Σ5, Σ31a) were constructed using Atomsk and subjected to temperature gradients of 500–1100 K and 600–1600 K, with a time step of 1 fs. Structural dynamics and migration behavior were analyzed using LAMMPS and visualized with the OVITO software, providing detailed insights into microstructural evolution under thermal gradients.

Context

Chelates of transition metal ions with amino acids and peptides are widely used in animal feeding. Methionine hydroxy analogue (MHA) was proposed as a replacement for amino acid methionine (MET) to solve stability problems within such applications and to provide extra anti-microbial benefits. In this study, chelation patterns of MHA with transition metal ions are investigated computationally. Bischelates are modeled as ML₂, where M = Mn⁺², Fe⁺², Cu⁺², Zn⁺² and L = MHA, CH₃SCH₂CH₂CH(OH)COO⁻. Coordination with structural water molecules was taken into account (ML₂.nH₂O) based on the experimental findings. A comparative analysis was performed with chelates of corresponding amino acid MET in the forms of MLA.nH₂O and MA₂.nH₂O, where A = MET, CH₃SCH₂CH₂CH(NH₂)COO⁻. Formation of dinuclear complexes by binding with the second metal atom was also investigated (M₂L₂.nH₂O). It was found that Cu⁺², Fe⁺², Zn⁺², and Mn⁺² form bischelates with both MET and MHA. DFT calculated complexation energy is highest for Cu⁺², in which binding contains more covalent contributions, and lowest for Mn⁺², in which binding is dominated by electrostatic interactions. A second metal ion might be involved to form dimetallic bischelates of MHA. This is favored by the chelates of Cu⁺², Fe⁺², and Zn⁺². On the other hand, Mn⁺² does not tend to form such dimetallic complexes. It was concluded that, in terms of the complexation energies, MHA can be used as a replacement for MET in feed supplements of livestock animals for Cu⁺², Fe⁺², and Zn⁺². On the other hand, for Mn⁺², MET might be a better choice in trade-off the antimicrobial properties of MHA.

Methods

DFT was used to model the chelate structures at the wB97-XD/6-31+G(d,p) level of theory. Gaussian 16 program was used for geometry optimizations. All molecules and chelates were optimized in aqueous environment to mimic the experimental conditions using the Polarizable Continuum Model (PCM) implemented in Gaussian program. Explicit water molecules were added to investigate the structural coordination. Electron density topology analyses within Quantum Theory of Atoms-in-Molecules (QTAIM) have been employed to reveal the nature of bonding interactions. AIMAll software package was used to analyze the electron density and topological critical points involved in chelation. Charge transfer was analyzed by NPA charges on metal ions. NCI Analysis was performed to understand the nature of non-covalent interactions better using Multiwfn and VPN softwares.

Context

Cucurbit[7]uril (CB[7]) host–guest systems display extraordinary binding affinities, yet predicting their thermodynamic profiles from first principles remains an open challenge. Standard implicit-solvent DFT methods systematically overestimate free energies of inclusion because they neglect structured portal hydration, protonation equilibria, and conformational averaging. Here, we present a hydration- and pH-aware DFT workflow that integrates portal microhydration, charge-state correction, and simple conformer averaging within a unified supramolecular thermodynamic framework. Benchmarking on a small set of canonical CB[7] guests spanning six orders of magnitude in affinity shows that the corrected model substantially reduces the discrepancy with experimental ITC data for these systems and provides chemically transparent insight into how electrostatic and hydrophobic driving forces partition across different classes of cationic guests.

Methods

All geometries were optimized using the ωB97X-D/def2-TZVP level of theory with SMD implicit solvation, augmented by 2–4 explicit water molecules at each CB[7] carbonyl portal to account for microhydration and rim desolvation effects. Guest protonation states were corrected using experimental pKₐ values within thermodynamic cycles, and multiple bound conformers were combined through Boltzmann weighting to recover ensemble-averaged free energies. Noncovalent interactions were analyzed via RDG/NCI isosurfaces, revealing dispersion-dominated stabilization in hydrophobic guests and electrostatic enhancement in charged ones. The resulting microhydration- and pH-corrected protocol substantially narrows the discrepancy between simple implicit-solvent DFT and experimental binding free energies for a small benchmark set of CB[7] complexes and provides a mechanistically transparent framework that can be extended and rigorously tested on broader host–guest libraries in future work.

Context

Oral squamous cell carcinoma (OSCC) is a malignant epithelial neoplasm that affects the head and neck region and contributes to around 84–97% of oral cancer. Aurora kinase A is a key regulator of cell cycle progression and mitotic spindle assembly, which plays a critical role in the development and progression of OSCC. Knockdown of AURKA suppresses cell proliferation, migration, and invasion, while inducing apoptosis and reactive oxygen species generation in oral squamous cell carcinoma. This highlights the functional significance of AURKA in tumor progression and supports its potential as a novel therapeutic target. This study focuses on the in silico evaluation of anticancer peptides (ACPs) as potential inhibitors of AURKA, aiming to identify novel peptide-based drugs for targeting oral cancer.

Methods

Using advanced computational techniques, including molecular docking, molecular dynamics simulation, and pharmacokinetics profiling, we have screened 116 ACPs to evaluate their binding affinity, structural stability, and effect of mutagenesis. Interestingly, it was observed that AIP19 peptide demonstrated high binding affinity of -1049.8 and exhibited strong binding affinity to the catalytic pocket of AURKA, forming key hydrophobic interactions with residues such as Leu139, Phe144, Val147, Leu210, and Trp277, along with hydrogen bonds involving Lys143, Pro214, and Glu260. These interactions highlight its potential as a promising peptide-based inhibitor. Using the in silico mutagenesis approach, several peptide variants of AIP19 were generated to study the impact of specific mutations on the binding affinity. The results indicated that AIP19 mutations, including F5W, V6Y, V9W and M11Y could potentially enhance the peptide’s binding affinity for AURKA. Furthermore, the drug likeness properties, low toxicity, and better biocompatibility of peptides highlight their potential as cancer-targeted therapeutics with minimal adverse effect. The stability and binding affinity of the AURKA-peptide complexes were evaluated using molecular dynamic simulation and MM GB/PBSA analysis. This study highlights the effectiveness of in silico methodologies in accelerating the discovery and optimization of peptide-based drugs. The identified ACPs represent a promising step toward the development of safe and effective therapeutics against OSCC, offering a novel approach to combat tumor progression that leverages structure-based peptide engineering to enhance binding affinity. This study lays the groundwork for future experimental validation of AIP19, highlighting its promise as a targeted therapeutic strategy for OSCC.

Context

We model a library of 36 π-conjugated small molecules of D–A–D and A′–D–A–D–A′ types, combining donor cores (6H-pyrrolo[3,4-b]pyrazine or thieno[3,4-b]pyrazine), central acceptors (benzo[1,2-c:4,5-c′]bis([1,2,5]thiadiazole) or [1,2,5]thiadiazolo[3,4-g]quinoxaline), and terminal acceptors (benzotriazole, isoindole, phthalimide, benzimidazole) each with or without cyano group. We evaluated frontier orbital energies, open-circuit voltage (V_oc), fill factor (FF), light-harvesting efficiency (LHE), short-circuit current density (J_sc), and power conversion efficiency (PCE) for all molecules, and analyzed reorganization energies, transition-density matrix/Hirshfeld descriptors, and charge-transfer parameters for selected cases. Across the library, optical gap ≈0.72–1.96 eV, LHE ≈0.32–0.90, FF ≈0.36–0.91, and V_oc ≈0.06–1.42 V. Cyano substitution stabilizes frontier orbital levels. Thieno[3,4-b]pyrazine and especially the [1,2,5]thiadiazolo[3,4-g]quinoxaline core favor higher LHE. Benzotriazole and isoindole terminals fine-tune HOMO/LUMO levels and lower reorganization energies by enhancing planarity. These frameworks consistently deliver top PCE, reflecting the synergy of larger V_oc, robust LHE, and favorable FF. Across selected compounds, S₁ state is predominantly locally excited (LE) with short-range donor-to-acceptor charge transfer, whereas higher singlets often show stronger charge transfer character. Collectively, these trends link donor depth, acceptor electron deficiency, and terminal substitution to key photovoltaic descriptors, providing rational guidelines for designing high-efficiency OPV materials.

Method

Molecular geometries were optimized and electronic properties calculated using DFT at the B3LYP/6-31G level with Gaussian 16. Excited-state properties were obtained with TD-DFT at the same level of theory. Transition-density matrix, Hirshfeld electron–hole analyses and charge transfer analyses were carried out with Multiwfn 3.8_dev.

Graphical Abstract