Journal of Molecular Modeling最新文献

{"title":"Structural, electronic, vibrational, and thermodynamic properties of a novel energetic ionic 2,6-diamino-1‑hydroxy-9H-purine-1,7-diium nitrate","authors":"Si-Jia Lei,&nbsp;Fu-Sheng Liu,&nbsp;Zheng-Tang Liu","doi":"10.1007/s00894-025-06490-w","DOIUrl":"10.1007/s00894-025-06490-w","url":null,"abstract":"<p>Nitrogen-rich energetic salts have garnered growing interest owing to their flexible molecular frameworks and adjustable energetic behavior, highlighting the importance of investigating energetic ionic compounds. However, theoretical studies on the newly synthesized nitrate-based energetic salt, 2,6-diamino-1-hydroxy-9H-purine-1,7-diium nitrate, remain scarce. In this work, first-principles calculations are employed to comprehensively explore its structural, electronic, vibrational, and thermodynamic characteristics. The optimized lattice parameters exhibit excellent agreement with available experimental X-ray diffraction data, confirming the reliability of the computational approach. The electronic characteristics are analyzed through the band structure and the partial density of states (PDOS) of atomic valence electrons. The phonon density of states and dispersion curves are plotted, and the contributions of different atomic groups are discussed in detail. Furthermore, characteristic vibrational modes are assigned, and the calculated infrared spectra show good consistency with experimental frequencies. Based on vibrational properties, thermodynamic functions including entropy (S), enthalpy (H), constant-volume heat capacity (C_V), and Debye temperature (Θ) are calculated as functions of temperature. These results not only bridge the current gap in experimental thermodynamic data for this compound but also provide theoretical insights and a valuable reference for future experimental validation and performance evaluation.</p><p>This work is based on first-principles calculations within the framework of density functional theory (DFT), using the CASTEP software. The exchange–correlation functional is treated using the Perdew-Burke-Ernzerhof (PBE) method within the generalized gradient approximation (GGA), along with Grimme’s dispersion correction.</p>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 9","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144914790","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":"Thermal decomposition mechanism of melamine via ReaxFF molecular dynamics simulation","authors":"Liang Song,&nbsp;Zheng Mei,&nbsp;Jing Ye,&nbsp;Tuo-Lun Ren,&nbsp;Xiao Ma,&nbsp;Tao Fang,&nbsp;De-Qiu Wang,&nbsp;Xue-Hai Ju","doi":"10.1007/s00894-025-06477-7","DOIUrl":"10.1007/s00894-025-06477-7","url":null,"abstract":"<div><h3>Context</h3><p>Melamine, widely employed as a high-efficiency flame retardant, exhibits an intricate high-temperature degradation mechanism that remains poorly understood. Comprehensive insight into its pyrolysis behavior is critical for advancing flame-retardant material design. This study employs ReaxFF molecular dynamics simulations to investigate melamine’s thermal decomposition, elucidating initial reaction pathways, intermediate species formation, and final product distribution. Results revealed that melamine undergoes three temperature-dependent reactions: dimerization, NH₂ elimination, and ring-opening reactions. At 2500 K, the initial decomposition pathways of melamine involve (i) NH₂ removal yielding C₃N₅H₄ radicals, (ii) direct cleavage forming C₂N₄H₄ and CN₂H₂, and (iii) NH₂-assisted dehydrogenation generating NH₃. The primary final products comprise NH₃, CN₂H₂, H₂, and HCN. Moreover, melamine undergoes a transition to an intermediate with an N-bridge structure, ultimately leading to the formation of a melem structure. This study enhances our understanding at the atomic level of the thermal decomposition mechanism of melamine. Future studies should focus on investigating melamine-based composite materials for the development of high-performance and environmentally friendly flame retardants.</p><h3>Methods</h3><p>Based on the open source software LAMMPS, this study verified the applicability of the C/H/N ReaxFF force field in the melamine system and studied the thermal decomposition behavior of melamine through reactive molecular dynamics (RMD) simulation. The simulation was performed under the canonical ensemble (NVT) with a damping time constant of 100.0 fs. The integration of the atomic equations of motion was implemented using the velocity-Verlet algorithm, and the total simulation time was 1.0 ns. The RMD simulation trajectory was post-processed using the ChemTrayzer program, and the bond order cutoff was set to 0.3 for molecular identification, thereby supporting species distribution analysis and reaction pathway identification.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 9","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144905205","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":"A comprehensive DFT study on piroxicam transition metal complexes (Mn, Fe, Co, Ni, and Zn): implications for computational drug design","authors":"Riaz Maira,&nbsp;Muhammad Azam,&nbsp;Ahmed Irfan,&nbsp;Muhammad Asim Raza Basra","doi":"10.1007/s00894-025-06483-9","DOIUrl":"10.1007/s00894-025-06483-9","url":null,"abstract":"<p>Computational approaches are instrumental in understanding the structural and electronic characteristics of drug metal complexes, thereby facilitating the rational deign of more effective pharmaceutical agents prior to experimental validation. The present work was designed to evaluate the drug-likeness and therapeutic potential, bioavailability, pharmacokinetics, and toxicity characteristics of piroxicam transition metal (Mn, Fe, Co, Ni, and Zn). Additionally, the comprehensive structural, electronic, and solvent-dependent behavior were investigated through theoretical analysis, with particular emphasis geometry optimizations and stabilization effects explored in solvents such as water, ethanol, and DMSO. Among the studied systems, the Co and Ni-piroxicam complexes exhibited the highest stabilization energy. HOMO–LUMO energy gaps and molecular electrostatic potential (MEP) maps indicate enhanced charge transfer characteristics, helping to identify reactive electrophilic and nucleophilic sites. These findings underscore the significant influence of solvent polarity and metal ion size on the physicochemical properties and potential bioavailability of metal drug complexes. The ADMET assessment also proved the safety profile coupled with no predicted toxicity, offering meaningful insights for rational drug design.</p><p>ADMET analysis was carried out using the ADMETlab 3.0 online web server to predict, pharmacokinetic behavior, and various toxicity aspects. Furthermore, the geometry optimization and frequency analyses were performed using DFT at the B3LYP/6-31G(d,p) level for non-metal atoms and SDD basis set for transition metals. Solvent effects (water, ethanol, and DMSO) were modeled using the SMD continuum model as implemented in the Gaussian 16. Key descriptors such as HOMO–LUMO energies, their energy gaps, molecular electrostatic potential (ESP), and thermodynamics metrics were computed by Multiwf, Jmol, and SHERMO, respectively.</p><p>DFT studies of transition metal-piroxicam (Mn, Fe, Co, Ni, and Zn) focusing on solvent effects on different parameters. Solvent-induced changes in reactivity and stability are analyzed using solvation energy, global descriptors, molecular orbitals, and thermodynamic parameters. Complementary ADMET and toxicity evaluations via ADMETlab3.0 provide insights into pharmacokinetics, drug-likeness, and safety profiles, supporting their potential in drug formulation and development.</p>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 9","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144897212","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":"Harnessing AI-driven reverse docking in drug discovery: a comprehensive review of opportunities, challenges, and emerging trends","authors":"Olanrewaju Ayodeji Durojaye,&nbsp;Sm Faysal Bellah,&nbsp;Henrietta Onyinye Uzoeto,&nbsp;Nkwachukwu Oziamara Okoro,&nbsp;Samuel Cosmas,&nbsp;Judith Nnedimkpa Ajima,&nbsp;Amarachukwu Vivian Arazu,&nbsp;Somtochukwu Precious Ezechukwu,&nbsp;Chiemekam Samuel Ezechukwu,&nbsp;Arome Solomon Odiba","doi":"10.1007/s00894-025-06480-y","DOIUrl":"10.1007/s00894-025-06480-y","url":null,"abstract":"<p>The integration of artificial intelligence (AI) with reverse docking methodologies is reshaping drug discovery by streamlining the identification of drug targets and therapeutic interactions. This approach is pivotal in drug repurposing, safety profiling, and predicting off-target effects. Reverse docking uniquely identifies potential binding sites across diverse protein targets, providing insights into drug efficacy and adverse outcomes. AI technologies, such as machine learning, deep learning, and reinforcement learning, enhance this workflow by optimizing target selection, virtual screening, and conformational sampling. Despite challenges like data limitations and algorithmic complexities, AI-driven reverse docking has shown promise in drug repurposing and precision medicine, as illustrated by successful case studies. This review highlights its transformative potential and future prospects, including the incorporation of multi-omics data and real-time discovery pipelines for personalized medicine.</p><p>The computational strategies discussed leverage reverse docking platforms integrated with AI frameworks. Machine learning and deep learning models were employed for target selection and interaction prediction, while reinforcement learning facilitated advanced sampling techniques. Virtual screening workflows incorporated AI-driven optimizations for docking simulations. These methodologies were implemented using widely recognized computational tools, including AI libraries and molecular docking software, ensuring robust and reproducible results. Challenges in data integration were addressed by employing high-throughput pipelines capable of processing multi-omics datasets, thus supporting comprehensive drug discovery initiatives.\u0000</p>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 9","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144893920","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":"The influence of mixed solvents on the morphology of ε-CL-20 crystal","authors":"Jianhua Wang,&nbsp;Shuya Wang,&nbsp;Jiaxuan Zhou,&nbsp;Hang Li,&nbsp;Yanwu Yu","doi":"10.1007/s00894-025-06476-8","DOIUrl":"10.1007/s00894-025-06476-8","url":null,"abstract":"<div><h3>Context</h3><p>CL-20 (especially the ε-crystal form) is a high-energy density explosive, but the preparation of centimeter-sized ε-CL-20 crystals is complex, which limits the study of its properties and mechanisms. Since crystal morphology can significantly affect the performance and sensitivity of energetic materials, this study combines MD simulation and experimental techniques to study and examine the differences in ε-CL-20 crystal habit as well as the interplay between the principal growing crystal planes of ε-CL-20 and the mixed solvent molecules. The findings reveal that according to the AE model, ε-CL-20 consists of (0 1 1), (1 1 0), (1 0 -1), (1 1 -1), (0 0 2), (0 2 1), and (1 0 1) seven independent surfaces under vacuum, and the (0 1 1) surface is the most important growth surface. During the crystallization process of ε-CL-20 in three mixed solvents, the (0 1 1) surface remains an important crystal surface due to its low modified attachment energy. Also, the impact of the solvent component on the morphology of the crystal is more significant compared to that of the non-solvent component. The size of the crystal cultured in the experiment can reach centimeter level and is consistent with the simulated morphology. The X-ray diffraction patterns show that the synthesized crystals were in the <i>ε</i> form, and the sections are (0 1 1) surface. This study provides a novel approach for cultivating large ε-CL-20 crystals, paving the way for further studies on its performance and mechanism.</p><h3>Methods</h3><p>The ε-CL-20 crystal morphologies were obtained within a vacuum and different binary mixed solvent environments under COMPASS force field utilizing the AE model via the MD method on the Materials Studio 2019 platform. The complete simulation was generated using the NTV system. The temperature control method was chosen as Anderson, whereas the temperature of the system was set as 298 K. The data were acquired after every 5000 steps and the step size was 1 fs, while the total time of the simulation was equal to 100 ps.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 9","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144893921","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":"Electrostatic field modulation of high-nitrogen heterocycles: a computational study on energy and stability","authors":"Peng Zhang,&nbsp;MengJie Bo,&nbsp;YuQin Chu,&nbsp;Yang Zhu,&nbsp;Peng Ma","doi":"10.1007/s00894-025-06482-w","DOIUrl":"10.1007/s00894-025-06482-w","url":null,"abstract":"<div><h3>Context</h3><p>In this study, the effect of external electric field (EEF) on three kinds of high nitrogen heterocyclic compounds with different ring structures (<b>PA-1 ~ 3</b>, oxadiazole, triazole, and tetrazole) was investigated by quantum chemical calculation. By using B3LYP/6-311G + (d, p) theory and Laplace bond order (LBO) analysis, the trigger bond was determined, and further EEF was applied along the <i>X</i>/<i>Y</i>/<i>Z</i> axis (0–0.02 a.u.) to study its effects on molecular structure, electron distribution, and DOS. The results show that EEF in different directions has a significant effect on charge transfer and intermolecular interaction, which provides a theoretical basis for regulating energy output and thermal stability. This work highlights the potential of computational strategies in the design of energetic materials with controllable properties, and builds a bridge between theoretical prediction and practical application in high-energy systems.</p><h3>Methods</h3><p>The Gaussian 16 software has been chosen for simulation and computation in this study. The B3LYP functional and 6-311G + (d, p) basis set has been utilized for the calculation and simulation of external electric fields, with the strength ranging from 0 to 0.020 a.u. and an increment gradient of 0.005 a.u.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 9","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894058","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 calculations based on 4,5-di(1,2,4-oxadiazol-3-yl)-2H-1,2,3-triazole and 3,3′ -(2H-1,2,3-triazole-4,5-diyl)-bis(1,2,4-oxadiazol-5(4H)-one) derivatives: a DFT study","authors":"Yang Zhu,&nbsp;Peng Zhang,&nbsp;YuQin Chu,&nbsp;Wen Jiang,&nbsp;Peng Ma,&nbsp;CongMing Ma","doi":"10.1007/s00894-025-06473-x","DOIUrl":"10.1007/s00894-025-06473-x","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Context&lt;/h3&gt;&lt;p&gt;1,2,3-Triazole has excellent thermal stability, and both 1,2,3-triazole and 1,2,4-oxazolium are good in structural modifiability. This study employed density functional theory (DFT) to design 24 target compounds (designated &lt;b&gt;PA-1&lt;/b&gt; to &lt;b&gt;PA-24&lt;/b&gt;) based on the characteristics of these two heterocyclic systems. Using 4,5-diallyl-2H-1,2,3-triazole-3,3′-(2H-1,2,3-triazole-4,5-diyl)-bis(1,2,4-oxadiazol-5(4H)-one) as the parent compound (labeled &lt;b&gt;A1&lt;/b&gt;), we introduced different energetic substituents at the C3 position of the oxadiazole ring and the N2 position of the triazole ring. Alternatively, using 3,3′-(2H-1,2,3-triazole-4,5-diyl)-bis(1,2,4-oxadiazol-5(4H)-one) as the parent compound (labeled &lt;b&gt;A2&lt;/b&gt;), we introduced different energetic substituents at the N2 position of the triazole ring. The selection process considered both macroscopic properties (heat of formation and detonation performance) and microscopic factors including frontier molecular orbitals, energy gaps, weak interactions, surface electrostatic potential, and bond parameters. This approach aimed to identify energetic materials with both detonation performance and safety characteristics while investigating how introducing different substituents at these two positions affects detonation performance and safety. The research results indicate the following: First, introducing an azide group at the C3 position of the oxadiazole in &lt;b&gt;A1&lt;/b&gt; more effectively enhances the compound’s heat of formation. &lt;b&gt;PA-13&lt;/b&gt; (△&lt;i&gt;H&lt;/i&gt;&lt;sub&gt;f,sold&lt;/sub&gt; = 972.97 kJ/mol), &lt;b&gt;PA-14&lt;/b&gt; (△&lt;i&gt;H&lt;/i&gt;&lt;sub&gt;f,sold&lt;/sub&gt; = 1023.62 kJ/mol), and &lt;b&gt;PA-15&lt;/b&gt; (△&lt;i&gt;H&lt;/i&gt;&lt;sub&gt;f,sold&lt;/sub&gt; = 1069.24 kJ/mol), which all contain azide groups, rank among the top three in heat of formation among the 24 compounds. Second, &lt;b&gt;PA-6&lt;/b&gt; (&lt;i&gt;D&lt;/i&gt; = 9.31 km/s, &lt;i&gt;P&lt;/i&gt; = 39.93 GPa, &lt;i&gt;Q&lt;/i&gt; = 7.39 kJ/g) exhibits the best detonation performance: its detonation pressure exceeds those of RDX (&lt;i&gt;G&lt;/i&gt; = 36GPa), its detonation velocity and detonation heat surpass that of HMX (&lt;i&gt;D&lt;/i&gt; = 9 km/s, &lt;i&gt;Q&lt;/i&gt; = 6.4 kJ/g), and it achieves the ideal state of zero oxygen balance, resulting in the highest energy utilization efficiency. Third, &lt;b&gt;PA-19&lt;/b&gt; showed the least impact sensitivity and showed the potential of an insensitive explosive. Fourth, hydrogen bonds are common in the molecular structure of &lt;b&gt;PA-8&lt;/b&gt; ~ &lt;b&gt;PA-12&lt;/b&gt; derivatives of &lt;b&gt;A2&lt;/b&gt;, which may contribute to the stability of the molecules. Fifth, trinitromethyl and dinitromethyl groups are more prone to fragmentation. The substituents introduced at the C3 position of the oxadiazole have almost no effect on the ring length of the oxadiazole, but introducing trinitromethyl at the N2 position of the triazole causes the triazole ring structure to expand, resulting in an increased ring length.&lt;/p&gt;&lt;h3&gt;Method&lt;/h3&gt;&lt;p&gt;All calculations in this paper are based on density functional theory and were performed using the Gaussian16 software. Initi","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 9","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144880944","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":"Sensing attributes of ethylbenzene and methyl ethyl ketone vapours using novel β-arsenic nitride nanosheets based on first-principles study","authors":"R. Chandiramouli,&nbsp;A. Varshini,&nbsp;V. Nagarajan","doi":"10.1007/s00894-025-06449-x","DOIUrl":"10.1007/s00894-025-06449-x","url":null,"abstract":"<div><h3>Context</h3><p>In this research study, we employed a novel group VA-VA two-dimensional material β-arsenic nitride (β-AsN) nanosheet to explore the adsorption behavior of ethylbenzene and methyl ethyl ketone using the density functional theory (DFT) method. Initially, the structural stability of the β-AsN is validated by formation energy and phonon band spectrum. With the influence of band structure and projected density of states (PDOS) spectrum, we investigated the electronic characteristics of β-AsN monolayer. The computed energy gap value of β-AsN is 3.427 eV, which shows its semiconducting nature, and it can be utilized for numerous applications, viz., chemical sensors, bio-sensors, and optoelectronic devices. Using the most significant factors, namely relative band gap variation, Mulliken charge transfer, and adsorption energy, the adsorption behavior of ethylbenzene and methyl ethyl ketone on β-AsN is studied. The adsorption energy range is observed to be (− 0.134 eV to − 0.820 eV), which confirms that a weak van der Waals force acts between the base material and pollutants. The overall outcomes claimed that the β-AsN can be efficiently utilized for detecting both ethylbenzene and methyl ethyl ketone molecules in the common air environment.</p><h3>Methods</h3><p>The electronic and structural properties of β-AsN monolayer are calculated using the Quantum ATK package. We used a hybrid generalized gradient approximation (GGA) level of theory and Becke-3-Lee–Yang–Parr (B3LYP) exchange–correlation functional during the calculation. Also, methyl ethyl ketone and ethylbenzene adsorption on β-AsN monolayer is analyzed using the DFT calculations by employing the empirical dispersion correction of Grimme (DFT-D3) owing to weak van der Waals interactions.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 9","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144880845","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":"Analysis and interpretation of experimental UV–Vis absorption spectra of benzochalcogenadiazoles and quinoxaline heterocycles through TDDFT","authors":"F. E. Jorge,&nbsp;M. J. S. Matos,&nbsp;A. A. Vieira,&nbsp;T. Cazati,&nbsp;B. B. Postacchini","doi":"10.1007/s00894-025-06460-2","DOIUrl":"10.1007/s00894-025-06460-2","url":null,"abstract":"<div><h3>Context</h3><p>Luminescent liquid crystals, particularly those derived from heterocyclic quinoxalines and benzochalcogenadiazoles, have garnered interest for their combined photophysical and mesomorphic properties. These compounds feature central heterocycles (selenium, oxygen, sulfur, or quinoxaline) connected to phenyl groups via triple bonds, with terminal alkoxy chains of uniform length. Their photophysical properties arise from conjugated systems involving delocalized electrons, while mesomorphic behavior depends on chain size and functional groups. This study performed a comparative analysis of experimental UV–vis absorption spectra against TDDFT computational calculations to clarify the photophysical properties of quinoxaline, 2,1,3-benzoxadiazole, 2,1,3-benzothiadiazole, and 2,1,3-benzoselenadiazole derivatives. Insights into the effects of scalar relativistic corrections and long-range functional adjustments on absorption energies are provided.</p><h3>Method</h3><p>Time-dependent density functional theory with the polarizable continuum model, available in the Gaussian 09 program, was used to simulate UV–Vis absorption spectra. Calculations utilized the CAM-B3LYP, B3LYP, and M062X functionals, along with basis sets incorporating scalar relativistic corrections via the Douglas-Kroll-Hess transformation. The impact of various functionals and the size of the basis set on the excitation energies was evaluated, especially for selenium-containing compound. The emission spectra in toluene were calculated with the ORCA 5.0.3 code. Experimental UV–Vis absorption and emission spectra were recorded in toluene for comparison with theoretical predictions to determine the most accurate computational approach.\u0000</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 9","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144868872","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":"ConPath 2.0: an optimized consensus strategy for assessing the potential pathogenicity of hRPE65 missense variants","authors":"Giulio Poli,&nbsp;Salvatore Galati,&nbsp;Marco Macchia,&nbsp;Tiziano Tuccinardi","doi":"10.1007/s00894-025-06481-x","DOIUrl":"10.1007/s00894-025-06481-x","url":null,"abstract":"<div><h3>Context</h3><p><i>h</i>RPE65 is an essential enzyme in the retinoid visual cycle. Numerous missense variants of <i>h</i>RPE65 have been linked to retinal disorders, such as retinitis pigmentosa and Leber congenital amaurosis. Moreover, many <i>h</i>RPE65 missense mutations are currently classified as variants of uncertain significance (VUS) due to insufficient evidence for a definitive pathogenicity classification. Addressing this limitation is critical for enabling accurate diagnoses and identifying suitable candidates for gene therapy. For this reason, we developed a <i>h</i>RPE65-tailored computational strategy, based on a consensus of multiple in silico pathogenicity predictions, enabling a rapid and reliable evaluation of the potential pathogenic effect of over 200 <i>h</i>RPE65 VUS. The analysis provided valuable insights to support the reclassification of these variants and assist clinicians in assessing their suitability for gene therapy.</p><h3>Methods</h3><p>In this study, we optimized our recently developed ConPath approach, which combines variant pathogenicity predictions from 19 different computational tools. In particular, we expanded the pool of predictive tools combined in the approach to 27, incorporated 3D-based methods that employ structural information for their prediction, and we refined the statistical framework for selecting the most reliable tools within an extended pool of more than 70 different methods. The tools were assessed based on their ability to discriminate pathogenic from benign <i>h</i>RPE65 missense mutations using an updated and expanded dataset of known <i>h</i>RPE65 variants. The resulting enhanced strategy, ConPath 2.0, was applied to the 210 <i>h</i>RPE65 VUS reported in the ClinVar database.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 9","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144880846","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}