Journal of Molecular Modeling最新文献

{"title":"How does the intramolecular proton transfer change on the partial change of the saturation characteristics in 8-hydroxyquinoline? A detailed computational study","authors":"Niranjan Biswas,&nbsp;Analabha Roy,&nbsp;Abhijit Chakraborty","doi":"10.1007/s00894-025-06524-3","DOIUrl":"10.1007/s00894-025-06524-3","url":null,"abstract":"<div><h3>Context</h3><p>Intramolecular proton transfer (IPT) has been investigated in 8-hydroxyquinoline (8-HQ) and one of its derivatives, 5,6-dihydroquinolin-8-ol (8-DQ). Computations identify the global minima as the enol (<b>E</b>) in S₀ and the proton transferred keto (<b>K</b>^<b>*</b>) form in S₁. The barrier for IPT process reduces on excitation.The pathway was investigated by altering IPT coordinate and intrinsic reaction coordinates (IRC). The frontier molecular orbital analysis shows the shift in electron distribution to the pyridine ring upon excitation. The OH stretching vibration shows a red shift upon <b>E</b> → <b>E</b>^<b>*</b> excitation, confirming the possibility of excited state intramolecular proton transfer (ESIPT). These molecules adhere to the maximum hardness principle (MHP) and the minimum electrophilicity principle (MEP). Natural bond orbital (NBO) analysis reveals the onset of hyperconjugative interactions involving the lone pair of N atom in S₁. Ring and bond critical points are identified. A mixed covalent and noncovalent character of the N₁···H₁₂ bonds signifies the onset of ESIPT. DFT computations with M06-2X and B3LYP functionals show some marked differences, particularly in terms of hydrogen bond lengths and charges, demanding experimental results to ascertain the choice of functionals.</p><h3>Methods</h3><p>DFT (B3LYP, M06-2X, and ωB97X-D functionals) and ab initio methods (MP2) are used in S₀ whereas CIS and TDDFT in S₁. 6–311 +  + G(d, p) and <i>aug</i>-cc-pVDZ are the corresponding basis sets used. The computations involve the Gaussian 09 program, which include NBO analysis. PED and QTAIM analyses are performed through the Veda 4 and Multiwfn programs.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 11","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theoretical investigation into molecular level encapsulation and active layer strategies with carbon dot integration for micro-sized photovoltaic cell","authors":"Azeez Ahamed,&nbsp;Piumantha Samaranayake,&nbsp;Lakshitha Madhushan,&nbsp;Muhammad Raziq Rahimi Kooh,&nbsp;K. R. Koswattage,&nbsp;Roshan Thotagamuge","doi":"10.1007/s00894-025-06518-1","DOIUrl":"10.1007/s00894-025-06518-1","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Context&lt;/h3&gt;&lt;p&gt;This s tudy explores the potential of functionalized carbon dots (CDs) for integration into the encapsulation and active layers of micro-sized photovoltaic cells (PVCs), with a focus on applications in renewable energy, biomedical devices, optoelectronics, and environmental sensors. Traditional photovoltaic materials such as perovskites and organic polymers, while efficient, pose challenges related to toxicity and environmental instability. In contrast, CDs derived from biocompatible sources offer enhanced safety and sustainability due to their high quantum yield, photostability, and tunable optical properties. Among the variants studied, amide-functionalized carbon dots (CD-CONH₂) were found optimal for encapsulation when paired with graphene (Gr-CD-CONH₂), while nitrogen-doped CD-CONH₂ (CD-CONH₂/N), integrated with silicon quantum dots (Si-CD-CONH₂/N), demonstrated superior characteristics for active layer performance. Key results include high HOMO–LUMO energy gaps of 3.50 eV (vacuum) and 3.48 eV (water) for CD-CONH₂, and 2.11–2.15 eV for Si-(CD-CONH₂/N), along with strong dipole moments and negative formation energies, indicating stability and efficiency across environments. These findings suggest that Gr-(CD-CONH₂) and Si-(CD-CONH₂/N) composites are promising materials for enhancing the environmental sustainability and performance of next-generation micro-sized PVCs.&lt;/p&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;All theoretical simulations were performed using &lt;i&gt;Gaussian 09W&lt;/i&gt;. Geometry optimizations and frequency analyses of functionalized CDs (-OH, -NO₂, -NH₂, -COOH, -CONH₂, -CHO) were conducted using the B3LYP-D3BJ functional with the 6-311G(d) basis set. Frequency analyses confirmed convergence by the absence of imaginary frequencies. Time-dependent DFT (TD-DFT) calculations were employed for UV–Vis spectral analysis using the TD-SCF method, with solvent effects modeled via the SMD approach (water as solvent). Water was selected as the solvent because our theoretical PVC model is intended to have potential biomedical relevance in non-invasive photodynamic treatments. In this context, water serves as a representation of the physiological environment of the human body. All TD-SCF calculations were done using default Gaussian settings for 10 excited states. Visualization and input generation were performed using &lt;i&gt;GaussView 6.0&lt;/i&gt;. Encapsulation studies involving CD-CONH₂ and graphene were initially modeled using &lt;i&gt;AutoDock Vina (SwissDock)&lt;/i&gt; to determine optimal binding poses, followed by full DFT optimization in &lt;i&gt;Gaussian 09W&lt;/i&gt;. Adsorption and solvation energies were computed using standard DFT protocols. For active layer modeling, the Si-(CD-CONH₂/N) composite underwent similar optimization and TD-DFT analysis. Reactivity descriptors (chemical hardness, softness, chemical potential, and electrophilicity) were derived from HOMO–LUMO energies. Additional analyses such as transition density matrix (TDM), electrostatic potential (","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 11","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145256502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular simulation of B-N systems: insights into the interactions and properties of borospherene–pyridine hybrids","authors":"Ling Pei,&nbsp;Li-Juan Zhang,&nbsp;Hai-Bo Yao","doi":"10.1007/s00894-025-06513-6","DOIUrl":"10.1007/s00894-025-06513-6","url":null,"abstract":"<div><h3>Context</h3><p>Borospherene (B₄₀), an all-boron fullerene analogue, exhibits Lewis acidity at its boron sites, while pyridine, a common organic ligand, acts as a Lewis base. Despite extensive research on B₄₀ interactions with metals and small inorganic molecules, the potential for functionalization with organic ligands like pyridine to form novel hybrid materials, such as borospherene–organic frameworks (BOFs), remains largely unexplored. This study investigates the structure, stability, and nature of interactions in B₄₀-pyridine (B₄₀-Py) complexes. Structural searches identified 18 isomers, with detailed analysis revealing that the most stable complexes form through direct B–N interactions. The B–N bonding exhibits a synergistic combination of covalent and ionic character, as evidenced by multiple computational analyses. The most stable isomer (involving B(4) site) provides crucial insights for designing B–N functional molecules and BOFs based on borospherene.</p><h3>Methods</h3><p>Density functional theory (DFT) calculations were performed using Gaussian 16. Initial structural searches employed the Molclus program coupled with xTB pre-optimization. Geometry optimizations and frequency calculations (confirming no imaginary frequencies) for isomers were carried out at the M062X/6-311G(d), PBE0-D3/6-311G(d), and B3LYP-D3/6-311G(d) levels, incorporating Grimme's D3 dispersion correction. Basis-set superposition error (BSSE) corrections were applied using the counterpoise method. Subsequent analyses for the six lowest-energy isomers included: electrostatic potential (ESP) mapping, quantum theory of atoms in molecules (AIM) analysis, charge-density difference analysis, and visualization of non-covalent interactions using the independent gradient model based on Hirshfeld partition (IGMH) and the interaction region indicator (IRI). These analyses utilized the Multiwfn 3.8 software package.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 11","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145256501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study of the pericyclic [2π + 4π] nature of a set of cheletropic reactions: analysis of the electronic reaction mechanism through bond reactivity descriptors and the electronic bonding structure","authors":"Jesús Sánchez-Márquez,&nbsp;Alejandro Morales-Bayuelo","doi":"10.1007/s00894-025-06510-9","DOIUrl":"10.1007/s00894-025-06510-9","url":null,"abstract":"<p>Cheletropic reactions are a class of pericyclic transformations with significant importance in synthetic organic chemistry. Traditionally explained through orbital symmetry considerations under the Woodward–Hoffmann rules, these reactions are often modeled using wavefunction-based methods. However, this study adopts an electron-density-centered approach, with the aim of providing a detailed description and explanation of the studied reactions using reactivity descriptors derived from Density Functional Theory. By analyzing electronic bonding structures, natural bond orbitals, and bond reactivity indices, we aim to offer a more detailed understanding of the stereoelectronic factors governing the [2π + 4π] nature of these processes. This framework enables the identification of subtle features such as charge delocalization and bond reorganization at the transition states, contributing to a refined theoretical model for pericyclic reactivity. The methodology may also support the rational design of new stereoselective reactions based on local electronic properties.</p><p>All quantum chemical calculations were performed using Gaussian 16. Geometries and vibrational frequencies were calculated at the B3LYP/6-31G(d,p) level to identify stationary points. IRC calculations with a stepsize of 0.1 amu¹/²·bohr confirmed the connectivity of transition states to reactants and products. Single-point energy refinements were carried out using the MPWB1K functional and the 6-311G(d,p) basis set. To obtain accurate electron densities, further calculations were performed at the CAM-B3LYP/aug-cc-pVTZ level. Natural bond orbital (NBO) analysis (v3.0) was used to evaluate donor–acceptor interactions via second-order perturbation theory. The Quantum Theory of Atoms in Molecules (QTAIM) was applied using AIMAll to locate and analyze bond critical points (BCPs). Non-covalent interactions (NCI) were examined with Multiwfn 3.8 to identify regions of weak interactions. Bond reactivity descriptors were computed using UCA-FUKUI v.2.1, a code based on conceptual-DFT and the electronegativity equalization principle. This method evaluates local reactivity without relying on atomic Fukui function partitioning, using bonding orbitals as the basis for descriptor calculation.</p>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 11","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145256619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural, optical, dielectric, and quantum-chemical investigation of glycine phosphite nanocrystals for optoelectronic application","authors":"Raja Mohan O S,&nbsp;P. Elaiyaraja,&nbsp;S. Shanmuga Sundari,&nbsp;S. Senthil,&nbsp;T. U. Jeevitha,&nbsp;V. Charles Vincent,&nbsp;Michael Ruby Raj","doi":"10.1007/s00894-025-06526-1","DOIUrl":"10.1007/s00894-025-06526-1","url":null,"abstract":"<p>Glycine phosphite (NH₃CH₂COOH·H₂PO₃) nanocrystals were synthesized through slow evaporation solution growth and rigorously analyzed for their optical, dielectric, and structural characteristics. X-ray diffraction validated a monoclinic structure (space group P2₁/c) with revised lattice parameters (<i>a</i> = 7.401 Å, <i>b</i> = 8.465 Å, <i>c</i> = 9.737 Å, <i>β</i> = 100.73°) and nanoscale crystallinity (43.5–90.1 nm). Microstrain values (0.00084–0.00211) and dislocation density (10¹⁴ lines/m²) demonstrated minimal lattice defects. The molecular stability of the –NH₃⁺, –COOH, and phosphate groups was confirmed using FTIR analysis, which identified their distinct vibrational signatures. The optical assessments confirmed the wide-bandgap dielectric properties, indicating direct and indirect band gaps of 5.32 eV and 5.24 eV, respectively. These findings highlight the material’s confirming strong UV transparency and excellent insulating behavior, with potential for high-frequency dielectric applications.</p><p>Quantum-chemical calculations were performed using density functional theory (DFT) at the B3LYP/6–311 +  + G(d,p) level with Gaussian 09 software. The computed HOMO–LUMO gap (5.27 eV) closely matched experimental values. Analyses of frontier molecular orbitals (FMO) and density of states (DOS) validated charge localization in accordance with insulating characteristics. NBO analysis revealed strong intermolecular charge transfer interactions [LP(2)O → π [(C = 0)], with stabilization energies reaching 56.8 kcal/mol, indicating improved electric delocalization and molecular stability. The Mulliken charge distribution showed strong polarization (P11: + 1.089e; O14: − 0.903 e), resulting in a dipole moment of 3.99 Debye. These findings show that hydrogen-bond-assisted charge transfer and polarization are the primary drivers of improved dielectric and optical performance. The global reactivity descriptors of chemical hardness (2.64 eV), electrophilicity index (1.94 eV), and electronegativity (3.20 eV) confirmed the experimental results of structural stability and wide-bandgap dielectric properties. Glycine phosphite nanocrystals outperform α-/γ-glycine and triglycine sulfate in UV transparency and band gap, suggesting their potential as advanced dielectric materials. These nanocrystals exhibit strong dielectric and UV-transparent properties.</p>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 11","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-principles investigation of 6H-SiC dominated by strong covalent bonding: electronic structure, mechanical properties and optical properties","authors":"Jing-Yi Xia,&nbsp;Zheng-Tang Liu,&nbsp;Qi-Jun Liu","doi":"10.1007/s00894-025-06528-z","DOIUrl":"10.1007/s00894-025-06528-z","url":null,"abstract":"<div><h3>Context</h3><p>Silicon carbide (SiC), a third-generation semiconductor, is renowned for its wide bandgap, exceptional thermal conductivity and high breakdown field. The unique ABCACB stacking atomic arrangement of hexagonal SiC (6H-SiC) induces direction-dependent electronic, optical, and mechanical responses, which are crucial for emerging applications. Using first-principles calculations, we comprehensively characterize these properties of 6H-SiC. Our findings reveal dual bandgaps (2.82 eV indirect and 4.16 eV direct), with dispersive band edges that are conducive to carrier transport. Further calculations indicate that the carrier effective mass along the (001) direction is smaller than (100) direction, and one key factor causing this anisotropy is the directional changes in sp³ hybridized orbitals due to the unique atomic stacking. DOS, Mulliken population and charge density studies collectively reveal the covalent-dominated bonding nature, which underpins its dispersive band edges, hard texture and brittleness. The wide direct bandgap and unique electronic structure contribute to its broad spectral transparency and low optical loss. Moreover, A strong directional dependence is observed in both the optical and mechanical properties of 6H-SiC, where the (001) direction demonstrates higher compressive stiffness and lower optical absorption and loss.</p><h3>Methods</h3><p>All calculations were conducted using density functional theory (DFT) as implemented in the CASTEP code, with norm-conserving pseudopotentials employed. For geometry optimization, we utilized the generalized gradient approximation with the Perdew-Burke-Ernzerhof (GGA-PBE) functional, whereas the electronic structure and optical characteristics were determined using the Heyd-Scuseria-Ernzerhof (HSE06) hybrid functional.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 11","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conceptual density functional theory in drug discovery: an overview","authors":"Hemangini Rohit,&nbsp;Hiteshi Tandon","doi":"10.1007/s00894-025-06487-5","DOIUrl":"10.1007/s00894-025-06487-5","url":null,"abstract":"<div><h3>Context</h3><p>As a development from Density Functional Theory, Conceptual Density Functional Theory (CDFT) has emerged as a valuable complementary approach in modern drug discovery. Both global and local chemical reactivity descriptors within the framework of CDFT have made it easier to study chemical reactions and how drugs affect their targets. They aid to predict the electronic properties of drug candidates, which simplifies the process of enhancing important characteristics such as their binding affinity, level of selectivity among others. They help in exploring and analyzing inhibitors that work specifically and allow to predict the negative effects those inhibitors may have. When applied with other approaches such as molecular docking and QSAR modeling, CDFT strengthens the whole drug discovery process. This review highlights the increasing importance of CDFT in rational drug design and especially in context of combined efforts with molecular docking and QSAR modeling. It also provides a fundamental knowledge of CDFT-based descriptors and their role in drug discovery process. In addition to highlighting existing challenges, this review outlines potential future directions.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 11","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular dynamics simulation of FOX-7 decomposition reaction under high temperature and pressure","authors":"Dandan Li,&nbsp;Wenpeng Wang,&nbsp;Jingzhao Cao,&nbsp;Qijun Liu","doi":"10.1007/s00894-025-06497-3","DOIUrl":"10.1007/s00894-025-06497-3","url":null,"abstract":"<div><h3>Context</h3><p>The decompositions of FOX-7 under high temperatures (2750–3750 K) and high pressures (0–50 GPa) were investigated using the ReaxFF-lg reactive force field molecular dynamics method, revealing its thermodynamic evolution and product formation mechanisms. The decomposition products are all NO₂, NO, N₂, H₂O, CO₂, HNCO, H₂, CO and NH₃, under high-temperatures and high-pressures conditions. Among these products, the intermediate products are NO₂ and NO, and the stabilization products are N₂, H₂O, CO₂, HNCO, H₂, CO and NH₃. And N₂ is consistently the most abundant product, while HNCO is the least abundant substance. In general, the yield of these products shows a positive correlation with temperature and a negative correlation with pressure. However, NH₃ content increases as pressure rises under high pressures. Additionally, FOX-7’s initial decomposition pathways are: C–NO₂ cleavage (yielding NO₂), N–O rupture (releasing O) and N–H dissociation (releasing H). This paper investigates the thermal decomposition behavior of FOX-7 under extreme conditions of high temperature and high pressure, revealing its decomposition pathway and providing support for the study of the decomposition behavior of other similar substances.</p><h3>Methods</h3><p>Molecular dynamics simulations of FOX-7 were performed using Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) with the ReaxFF-lg force field. A 2 × 4 × 2 supercell was constructed based on X-ray diffraction data, optimized geometrically (0.1 fs time step), equilibrated via NVE ensemble (10 ps, heated from 0 to 300 K) and NPT ensemble (15 ps, 300 K), verifying the applicability of ReaxFF-lg. To study high-temperature and high-pressure effects on FOX-7 thermal decomposition, two approaches were used. First, under NVE ensemble, the system was heated to target temperatures (2750—3750 K.) over 150 ps, then maintained for 150 ps (0.1 fs step, periodic boundaries). Second, initial pressures (0–50 GPa) were applied at 300 K via NPT ensemble for 20 ps, followed by heating to 3500 K over 50 ps under NVE. Atomic trajectories, species, and thermodynamic data were recorded every 10 fs.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 11","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145210537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico identification of anticancer flavonoids as dengue virus replication inhibitors: a molecular docking and simulation approach","authors":"Soumendu Patra,&nbsp;Arindam Paul,&nbsp;Harshita Shand,&nbsp;Sayan Ghosal,&nbsp;Suvankar Ghorai","doi":"10.1007/s00894-025-06516-3","DOIUrl":"10.1007/s00894-025-06516-3","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Context&lt;/h3&gt;&lt;p&gt;Dengue, a mosquito-borne viral disease endemic to over 100 countries, poses a serious health risk to people living in tropical regions. The viral non-structural proteins NS3 (helicase) and NS5 (RNA-dependent RNA polymerase) are critical targets for antiviral drug development. Several natural and synthetic compounds have been tried against this for the screening of antiviral inhibitor(s) but so far limited success has been achieved. In this study, we have investigated how natural products interact with and destabilize NS3 and NS5. We used in silico methods to screen new potential NS3 and NS5 inhibitors from various anti-cancer flavonoid compounds that previously showed anti-cancer properties in vitro. A virtual screening was conducted on 329 anti-cancer flavonoid compounds, selecting 190 compounds based on Lipinski’s rule of five, the Muegge filter, the Ghose filter, and the Veber filter. Molecular docking techniques allowed us to identify Artobiloxanthone (PubChem CID: 46887866) as the most effective binder for NS3, while Glabridin (PubChem CID: 124052) emerged as the most effective binder for NS5. These leading candidates demonstrated favorable ADMET profiles. Additionally, molecular dynamics (MD) simulations of up to 1000-ns showcased stable protein–ligand interactions, with convergence achieved at 200 ns for NS3 and 470 ns for NS5. The structural stability of the complexes was validated by analyzing root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA), and hydrogen bonding (H-bonding). Binding affinity between the ligand and target proteins was further validated by binding free energy calculations using the Molecular Mechanics Poisson–Boltzmann Surface Area (MM-PBSA) approach, providing a robust estimation of interaction stability. These findings highlight the potential of Artobiloxanthone and Glabridin as promising inhibitors of dengue virus replication.&lt;/p&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;The Chimera v1.11.2 program was employed for protein optimization, while PyRx 0.8 served for molecular docking. Protein structures were converted into.pdbqt format, and ligands were energy-minimized using the MMFF94 force field and conjugate gradient optimization. Visualization was conducted using BIOVIA Discovery Studio Visualizer and PyMOL. The ADMET properties of the top hits were predicted using the pkCSM and ProTox-II platforms. To address missing residues in the crystal structures, AlphaFold2 was used to predict full-length protein models. MD simulations were performed with the GROMACS 2024.5 package, utilizing the AMBER-f99SB-ILDN force field, the TIP3P water model, and a 120 mM NaCl concentration. Equilibration was achieved through V-rescale and C-rescale thermostats, followed by Parrinello–Rahman barostat production runs. Analysis of the MD trajectories included RMSD, RMSF, Rg, SASA, H-bonding, and MM-PBSA utilizing GROMACS tools, gmx_MMPBSA, VMD, and MDAna","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 11","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145210538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantum chemical study on the weak intermolecular interaction between 3,4-bis(3-nitrofurazan-4-yl) furoxan (DNTF) and microcrystalline wax","authors":"Jianfei Xu,&nbsp;Zhiwei Han,&nbsp;Yaning Li,&nbsp;Yuanlin Fan,&nbsp;Jianing Zhang","doi":"10.1007/s00894-025-06512-7","DOIUrl":"10.1007/s00894-025-06512-7","url":null,"abstract":"<div><h3>Context</h3><p>Compatibility is a key factor restricting the engineering applications of 3,4-Bis(3-nitrofurazan-4-yl) furoxan (DNTF). To establish a scientific criterion for the compatibility of DNTF with other substances, this study uses the DNTF/WAX system as the research subject. By applying computational chemistry methods, it reveals the interactions and incompatibility mechanism between DNTF andMicrocrystalline Wax (MW). Molecular surface electrostatic potential studies indicate that electrostatic interactions exist between the side of DNTF away from the oxygen atom on the furazan ring and the side of MW containing alcoholic hydroxyl groups. IGMH analysis further reveals that these weak interactions consist of hydrogen bonding and van der Waals forces. AIM calculations reveal that the weak interactions at the bond critical points (BCPs) in the DNTF/MW system are primarily \"weak\"-level hydrogen bonds of the N···H-O type and hydrogen-bond-like interactions of the O···H-C type. Frontier molecular orbital (FMO) analysis reveals that compared with pure DNTF, the molecular orbital energy level difference ΔE of the DNTF/MW composite structure decreases by 21%. This indicates enhanced reactivity of the composite structure. Mayer bond order analysis verifies the accuracy of the FMO results: in the DNTF/MW composite structure, the bond orders of both the key pyrolysis initiation bond (O6-N3) and secondary initiation bonds decrease to varying degrees compared to the single-component DNTF. This study provides a theoretical basis for screening DNTF-based mixed explosive formulations and helps improve the safety of DNTF in practical applications.</p><h3>Methods</h3><p>The initial molecular structures of DNTF and MW used in this study were retrieved from the Cambridge Crystallographic Data Centre (CCDC) and optimized using Gaussian16 software at the B3LYP-D3/6-311G(d,p) computational level. To obtain the optimal bimolecular conformations of DNTF and MW, a conformational search method was employed: first, the Genmer package was used to generate 500 bimolecular configurations of DNTF/MW composites; then, the Molclus program was employed to invoke XTB software for structural optimization at the GFN2-xTB level, with five configurations of lower energy retained; subsequently, Gaussian16 software was called to perform optimization and frequency calculations for these structures at the B3LYP-D3(BJ)/6-31G* level; finally, the ORCA software was used to perform single-point energy calculations at the PWPB95-D3(BJ)/def2-TZVPP level for the structures optimized by Gaussian, thereby obtaining the free energy of each configuration, and the configuration with the lowest energy was selected based on the free energy for subsequent weak interaction analysis. Additionally, the counterpoise (CP) method was also used to correct for basis set superposition error (BSSE).</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 11","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145210636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}