Journal of Molecular Modeling最新文献

{"title":"Molecular insights into hydrogen adsorption on F-functionalized MXenes: a combined GCMC and molecular dynamics study","authors":"Fatemeh Zarei,&nbsp;Leila Lotfikatooli","doi":"10.1007/s00894-026-06701-y","DOIUrl":"10.1007/s00894-026-06701-y","url":null,"abstract":"<div><h3>Context</h3><p>The increasing demand for sustainable energy carriers highlights the need for safe and efficient hydrogen storage materials. MXenes, owing to their layered structure and tunable surface chemistry, have emerged as promising candidates for solid-state hydrogen storage. In this study, hydrogen adsorption on Ti–C–based MXenes is systematically investigated with particular emphasis on the role of fluorine surface termination. The results show that pristine Ti–C MXene exhibits limited hydrogen uptake, whereas fluorine termination significantly enhances adsorption performance. Aluminum atoms, inherently present in the MXene-based structures considered, mainly contribute to the structural stability of the layered framework. A mixed Ti–C–Al–F configuration shows good agreement with available experimental data, particularly at higher pressures. Structural and dynamical analyses reveal pronounced H₂–F interactions and reduced hydrogen mobility near the MXene surface, while the calculated heats of adsorption indicate a physisorption-dominated mechanism favorable for reversible hydrogen storage. These findings provide a unified molecular-level understanding that links adsorption thermodynamics and diffusion behavior in MXene-based hydrogen storage systems.</p><h3>Methods</h3><p>Hydrogen adsorption was studied using a combined Grand Canonical Monte Carlo and molecular dynamics simulation approach implemented in the Materials Studio 2017 software package. GCMC simulations were used to generate adsorption isotherms at 298 K and pressures up to 35 bar, while molecular dynamics simulations were performed to analyze adsorption sites, diffusion behavior, and host–guest interactions. Interatomic interactions were described using classical force-field methods, with the Universal Force Field applied to MXene atoms and a rigid molecular model used for hydrogen.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758271","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":"Mechanistic insights into the thermal decomposition of hexamethyldisilane: a reactive molecular dynamics study","authors":"Jieshun Zhang,&nbsp;Minglin Li,&nbsp;Ruoyu Hong,&nbsp;Chuanhao Dong","doi":"10.1007/s00894-026-06721-8","DOIUrl":"10.1007/s00894-026-06721-8","url":null,"abstract":"<div><h3>Context</h3><p>Hexamethyldisilane (HMDS) serves as a critical single-source precursor for the chemical vapor deposition (CVD) of silicon carbide (SiC), yet its atomic-level pyrolysis mechanism and the kinetics of radical generation remain unclear. This study investigates the thermal decomposition behavior of HMDS to provide theoretical guidance for optimizing SiC deposition processes. The results demonstrate that HMDS pyrolysis follows first-order kinetics with an apparent activation energy of 44.47 kcal/mol, a value significantly lower than the theoretical dissociation energy of the Si–Si bond. By combining this kinetic data with reaction pathway analysis, it is concluded that the decomposition is governed by a multistep cooperative mechanism rather than simple homolytic bond cleavage. The reaction proceeds through three distinct stages: initial precursor decomposition dominated by C–Si bond dissociation, secondary reactions of intermediates involving cascading demethylation, and small-molecule formation accompanied by radical recombination. Methyl radicals (CH₃) are identified as the primary chain carriers, which are ultimately converted into thermodynamically stable methane (CH₄) via hydrogen abstraction. Furthermore, temperature is found to critically regulate the generation and accumulation behavior of CH₃ radicals.</p><h3>Methods</h3><p>Density functional theory (DFT) calculations were carried out with Gaussian 16 at the unrestricted ωB97XD/6-311G(d,p) level to optimize geometries and train the force field. A broken-symmetry strategy with guess = (mix,always) and nosymm was adopted to reliably describe bond dissociation and radical behaviors. Using the high-quality DFT data, the ReaxFF force field was further optimized. Reactive molecular dynamics simulations were then performed in LAMMPS with the optimized potential under the NVT ensemble at 2500–4000 K with a 0.1-fs time step. A cubic box with 100 HMDS molecules and periodic boundary conditions was adopted, and each condition was run three times for statistical reliability.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759323","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 evaluation of selected triterpenes as potential inhibitors of BRAF and BRAFV600E kinases for cancer treatment","authors":"Giovanny Aguilera-Durán,&nbsp;Alex Rivera-Vargas,&nbsp;Beatriz Hernández-Estrada,&nbsp;J. M. Alvarez-Baltazar,&nbsp;Brenda V. Loera-García,&nbsp;Ma Del Refugio Cuevas-Flores,&nbsp;Antonio Romo-Mancillas","doi":"10.1007/s00894-026-06729-0","DOIUrl":"10.1007/s00894-026-06729-0","url":null,"abstract":"<div><h3>Context</h3><p>BRAF kinases are involved in cancer cell survival and metastasis. Mutations in BRAF are frequent in several types of cancer, occurring in more than 50% of melanomas, 50–70% of thyroid cancers, 15% of colorectal cancers, and 5–8% of non-small-cell lung cancers. The most prevalent mutation is V600E. Vemurafenib and dabrafenib are two selective BRAF inhibitors approved by the FDA for clinical use. However, due to the increasing resistance to current kinase inhibitors, there is an urgent need to identify new molecular scaffolds with potential BRAF inhibitory activity. In this work, molecular docking, molecular dynamics, and metadynamics simulations were performed on twelve triterpenes to identify the best ligands with potential binding to BRAFWT and BRAFV600E. The interaction profiles of the selected triterpenes revealed key contacts with residues ILE463, THR529, GLN530, TRP531, CYS532, and PHE583, which contribute to stabilizing the conformation of both inhibitors and triterpenes within the catalytic binding site of the proteins. The ΔG of betulinic acid (−57.46 kcal/mol) in complex with BRAFWT is comparable to the BRAF inhibitors vemurafenib-OMe and dabrafenib reported in previous work, the ΔG of β-amyrin (−51.83 kcal/mol) showed a ΔG comparable to the inhibitors with BRAFV600E; moreover, the ΔG of lupeol (−62.43 kcal/mol) and moronic acid (−61.05 kcal/mol) are more favorable with BRAFV600E than vemurafenib-OMe and dabrafenib. These computational calculations allow us to consider these triterpenes as potential candidates for drug design cycles and to optimize the binding profile for the development of new selective inhibitors for BRAFV600E to cancer treatments.</p><h3>Methods</h3><p>Molecular docking calculations using AutoGrid 4.2.6, AutoDockGPU 1.5.3, and AutoDockTools 1.5.6 were performed. Molecular dynamics and metadynamics simulations were performed in the Desmond module of the academic version of the Schrödinger-Maestro 2021-4 program, utilizing the OPLS-2005 force field. Finally, all the protein figures presented in this article were made in the PyMOL program and the RMSD graphics were made in the statistical package R and RStudio 2025.05.1.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759258","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 CL20/4-bromo-3,5-dinitro-1-methylpyrazole (BMDNP) eutectic-based PBXs","authors":"Yu Yang,&nbsp;Bao-guo Wang,&nbsp;Li Yang,&nbsp;Xiong-bo Feng,&nbsp;Xing-Ming Liu,&nbsp;Ji-hang Du","doi":"10.1007/s00894-026-06640-8","DOIUrl":"10.1007/s00894-026-06640-8","url":null,"abstract":"<div><h3>Context</h3><p> CL-20/BMDNP eutectic explosive is a late-model explosive with excellent energy density and detonation parameters, but it still has higher sensitivity than TATB and FOX-7. In an attempt to reduce the sensitivity of CL-20/BMDNP eutectic explosive, a CL20/BMDNP eutectic model was installed in the paper. Polymer-bonded explosives (PBXs) were obtained by adding five different types of polymers, such as butadiene rubber (BR), ethylene-vinyl acetate copolymer (EVA), polyethylene glycol (PEG), fluoropolymer (F₂₆₀₃), and polyvinylidene difluoride (PVDF), to six cleavage surfaces(1 0 0), (0 0 1),(0 1 1),(0 −1 1), (1 1 0), and (1 −1 0), respectively. The sways of various polymers on the stability, trigger bond length, mechanical properties, and detonation properties of PBXs were predicted. The CL-20/BMDNP/PEG model has maximum binding energy and minimum trigger bond length among the five PBX models, manifesting that the CL-20/BMDNP/PEG model has tip-top stability, compatibility, and lowest sensitivity. Besides, despite the CL-20/BMDNP/F₂₆₀₃ model exhibiting exceptional detonation competences, it is supposed to denote that this model revealed a low level of compatibility. In conclusion, the CL-20/BMDNP/PEG model showed better integrated capacities, indicating that PEG is a more appropriate binder choice for PBXs on the basis of the CL-20/BMDNP cocrystal.</p><h3>Methods</h3><p>The molecular dynamics (MD) simulation method was used to investigate the properties of CL-20/BMDNP eutectic and its PBXs composites. All simulations were performed in the Materials Studio software platform. The COMPASS force field suitable for energetic materials was selected in the simulation process. The system was first equilibrated under the Isothermal-isobaric (NPT) ensemble at 295 K; the simulation duration was 2 ns, and the integration step was 1 fs.\u0000</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759336","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":"B4-engine as the rotational driver of the B13+ cluster: study based on BOMD analysis","authors":"Sourav Ranjan Ghosh,&nbsp;Sasthi Charan Halder,&nbsp;Atish Dipankar Jana","doi":"10.1007/s00894-026-06714-7","DOIUrl":"10.1007/s00894-026-06714-7","url":null,"abstract":"<div><h3>Context</h3><p>Boron clusters are of significant interest due to their inherent fluxionality and aromaticity. Among them, the B₄ unit exhibits a unique dynamic behavior, interconverting between a square-shaped transition state (TS, D_4h) and a diamond-shaped ground state (GS, D_2h). This dynamic motif also plays a pivotal role within the cationic B₁₃⁺ molecular rotor, where the B₄ subunit acts as a driving element in the rotational motion of the outer B₁₀ ring around the inner B₃ core which are analogous to the rim and axle of a wheel. The present study aims to establish a dynamic correlation between the isolated B₄ cluster and that of the B₁₃⁺ cluster containing embedded B₄ units within it, using Born–Oppenheimer Molecular Dynamics (BOMD) simulations. The key observation is a recurring diamond-square–diamond (DSD) to diamond-diamond (DD) transformation involving multiple B₄ units, which governs the stepwise rotation of the B₁₃⁺ cluster. By comparing the timescales and change in bonding pattern studied through AdNDP analysis, a direct correspondence between dynamics of isolated B₄ cluster and that of B₁₃⁺ cluster has been revealed. This study highlights the fundamental role of the intrinsic dynamics of the B₄ unit in orchestrating the collective rotational behavior of the B₁₃⁺ molecular rotor containing multiple B₄ subunits.</p><h3>Methods</h3><p>All quantum chemical calculations were carried out using Density Functional Theory (DFT) as implemented in Gaussian 09 (Revision D.01). Geometry optimizations and frequency analyses were performed using the PBE1PBE hybrid functional in conjunction with the 6-311+G(d) basis set. To ensure accurate determination of stationary points, a superfine integration grid and very tight convergence criteria were applied throughout. Minimum energy structures (N_Imag = 0) and transition states (N_Imag = 1) for both the B₄ and B₁₃⁺ clusters were identified based on vibrational frequency analysis. Born–Oppenheimer Molecular Dynamics (BOMD) simulations were also performed within Gaussian 09 to investigate the real-time structural dynamics of the clusters. Simulations were conducted under an NVE ensemble by coupling the system to a thermal reservoir at 150 K. Each cluster was propagated over a 5000-fs timescale to capture thermally driven transformations. To explore the bonding evolution during structural transitions, Adaptive Natural Density Partitioning (AdNDP) analysis was conducted using the Multiwfn3.8 program. Electron density distribution plots were also generated via Multiwfn to visualize bonding changes and electronic flux during dynamic processes.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759320","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":"Suppressing viral assembly in human metapneumovirus by targeting fusion protein with natural compounds: a structural dynamics and energetics study","authors":"Amit Dubey,&nbsp;Manish Kumar,&nbsp;Aisha Tufail","doi":"10.1007/s00894-026-06731-6","DOIUrl":"10.1007/s00894-026-06731-6","url":null,"abstract":"<div><h3>Context</h3><p>Human metapneumovirus (HMPV) is a significant cause of acute lower respiratory tract infections, particularly among pediatric, elderly, and immunocompromised populations, with no approved targeted antiviral therapy currently available. The prefusion conformation of the viral fusion (F) glycoprotein (PDB ID: 5WB0) is essential for membrane fusion and viral entry, representing a promising therapeutic target. In this study, a structurally diverse library of natural compounds was systematically screened to identify potential inhibitors of the HMPV F protein.</p><h3>Methods</h3><p>An integrated computational framework combining virtual screening, molecular docking, long-timescale molecular dynamics (MD) simulations, and density functional theory (DFT) calculations was employed. Virtual screening and docking were performed using AutoDock Vina, followed by rigorous binding pose validation. The top-ranked compounds—epigallocatechin gallate (EGCG), rutin, and quercetin—were subjected to 1000 ns MD simulations (in triplicate) using GROMACS 2022 with explicit solvent conditions (TIP3P water model, physiological ionic strength). Binding free energies were estimated via MM-GBSA, and residue-level dynamics were analyzed using RMSD, RMSF, and dynamic cross-correlation matrices. Electronic properties were evaluated at the B3LYP/6-31G(d,p) level using Gaussian 16, including HOMO–LUMO gap analysis and molecular electrostatic potential (MEP) mapping. Pharmacokinetic and toxicity profiles were predicted using SwissADME, pkCSM, and ProTox-II.</p><h3>Results</h3><p>Docking analysis revealed that EGCG, rutin, and quercetin exhibit stronger binding affinities than the reference antiviral ribavirin, driven by extensive hydrogen bonding, π–π stacking, and van der Waals interactions within the functional binding pocket of the F protein. MD simulations demonstrated enhanced structural stability of these complexes, with EGCG showing the lowest conformational deviation and most favorable binding free energy. Correlated residue motion analysis further indicated ligand-induced stabilization of key functional regions. DFT-derived electronic descriptors, including reduced HOMO–LUMO gaps and favorable electrostatic distributions, supported the high reactivity and binding propensity of the selected compounds. ADMET predictions suggested acceptable pharmacokinetic profiles with low predicted toxicity.</p><h3>Conclusion</h3><p>This study identifies EGCG, rutin, and quercetin as promising natural inhibitors of the HMPV fusion protein, providing mechanistic insights into their binding behavior and stability. These findings offer a strong computational foundation for further experimental validation and rational antiviral drug development targeting HMPV.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758918","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":"Building molecular C10-π-cationic interaction systems for reporting quadrupole moments basis","authors":"Abrar U. Hassan,&nbsp;Sajjad H. Sumrra,&nbsp;Mamduh J. Aljaafreh","doi":"10.1007/s00894-026-06716-5","DOIUrl":"10.1007/s00894-026-06716-5","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Context&lt;/h3&gt;&lt;p&gt;The engineering of supramolecular π–cation interaction systems can offer a route to enhance nonlinear optical (&lt;i&gt;NLO&lt;/i&gt;) properties. In this work, molecular &lt;i&gt;C&lt;/i&gt;&lt;sub&gt;&lt;i&gt;10&lt;/i&gt;&lt;/sub&gt; systems, externally doped with alkali (&lt;i&gt;Li, Na, K&lt;/i&gt;) and alkaline earth metals (&lt;i&gt;Be, Mg, Ca&lt;/i&gt;) are investigated computationally to quantify quadrupole moments and hyperpolarizabilities (&lt;i&gt;β&lt;/i&gt;&lt;sub&gt;&lt;i&gt;0&lt;/i&gt;&lt;/sub&gt;&lt;i&gt;)&lt;/i&gt;. The &lt;i&gt;C&lt;/i&gt;&lt;sub&gt;&lt;i&gt;10&lt;/i&gt;&lt;/sub&gt; exhibits a large &lt;i&gt;HOMO&lt;/i&gt;–&lt;i&gt;LUMO&lt;/i&gt; gap (&lt;i&gt;E&lt;/i&gt;&lt;sub&gt;&lt;i&gt;gap&lt;/i&gt;&lt;/sub&gt;) (4.05 eV), high hardness (&lt;i&gt;η&lt;/i&gt;, 2.03 eV), and negligible &lt;i&gt;β&lt;/i&gt;&lt;sub&gt;&lt;i&gt;0&lt;/i&gt;&lt;/sub&gt;, consistent with stability and low reactivity. The doping alters &lt;i&gt;C&lt;/i&gt;&lt;sub&gt;&lt;i&gt;10&lt;/i&gt;&lt;/sub&gt; dramatically as &lt;i&gt;Na@C&lt;/i&gt;&lt;sub&gt;&lt;i&gt;10&lt;/i&gt;&lt;/sub&gt; shows highest &lt;i&gt;β&lt;/i&gt;&lt;sub&gt;&lt;i&gt;0&lt;/i&gt;&lt;/sub&gt; (17,105 &lt;i&gt;a.u&lt;/i&gt;.) and strongest quadrupole distortion (–8.97 × 10&lt;sup&gt;17&lt;/sup&gt; Å), while &lt;i&gt;Mg@C&lt;/i&gt;&lt;sub&gt;&lt;i&gt;10&lt;/i&gt;&lt;/sub&gt; yields the lowest &lt;i&gt;E&lt;/i&gt;&lt;sub&gt;&lt;i&gt;gap&lt;/i&gt;&lt;/sub&gt; (0.19 eV), reflecting extreme reactivity but moderate optical response. In contrast, &lt;i&gt;K@C&lt;/i&gt;&lt;sub&gt;&lt;i&gt;10&lt;/i&gt;&lt;/sub&gt; exhibits the weakest enhancement (&lt;i&gt;β&lt;/i&gt;&lt;sub&gt;&lt;i&gt;0&lt;/i&gt;&lt;/sub&gt; = 254 &lt;i&gt;a.u&lt;/i&gt;.), and &lt;i&gt;Ca@C&lt;/i&gt;&lt;sub&gt;&lt;i&gt;10&lt;/i&gt;&lt;/sub&gt; positive quadrupole (+ 1.49 × 10&lt;sup&gt;17&lt;/sup&gt; Å) highlights a distinct charge redistribution mechanism. Global reactivity parameters confirm enhanced softness (&lt;i&gt;σ&lt;/i&gt;) (up to 1.68 for &lt;i&gt;Na@C&lt;/i&gt;&lt;sub&gt;&lt;i&gt;10&lt;/i&gt;&lt;/sub&gt;) and reduced ionization potentials (0.29 eV for &lt;i&gt;Mg@C&lt;/i&gt;&lt;sub&gt;&lt;i&gt;10&lt;/i&gt;&lt;/sub&gt;).&lt;/p&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;Density functional theory (DFT) calculations are performed with PBE-D3/def2-TZVP level, with electronic spectra evaluated via TD-DFT. Quadrupole moments (&lt;i&gt;Q&lt;/i&gt;&lt;sub&gt;&lt;i&gt;zz&lt;/i&gt;&lt;/sub&gt;), polarizabilities (α), and hyperpolarizabilities (&lt;i&gt;β&lt;/i&gt;) are computed, alongside, transition density matrix (TDM), hole–electron overlap, and charge density difference (&lt;i&gt;CDD&lt;/i&gt;) studies. Quadrupole moments were computed as the Q&lt;sub&gt;zz&lt;/sub&gt; component of the traceless Cartesian quadrupole tensor, as implemented in Gaussian 09 (using the keyword “pop = full”). The Q&lt;sub&gt;zz&lt;/sub&gt; values are reported in Debye•Å (D•Å), which is the SI-compatible unit for molecular quadrupole moments (1 D•Å = 3.336 × 10–30 C•m&lt;sup&gt;2&lt;/sup&gt;). To facilitate comparison with literature, the values are scaled by a factor of 10&lt;sup&gt;1&lt;/sup&gt;⁷ and tabulated in Table 1 as Q&lt;sub&gt;zz&lt;/sub&gt; /10&lt;sup&gt;1&lt;/sup&gt;⁷ D•Å. The Q&lt;sub&gt;zz&lt;/sub&gt; component was selected because the molecular principal axis of C10 and all doped systems lies along the z-axis, making Q&lt;sub&gt;zz&lt;/sub&gt; the most physically meaningful descriptor of axial charge redistribution upon metal doping. This definition, unit system, and conversion factor are now explicitly stated in Table 1 caption. The global reactivity parameters (IP, EA, &lt;i&gt;χ, μ, η, σ, ω&lt;/i&gt;) are derived using Koopmans theorem, and density of states (DOS) spectra are generated.\u0000&lt;/p&gt;&lt;h3&gt;Graphical Abstract&lt;/h3&gt;\u0000&lt;div&gt;&lt;figure&gt;&lt;div&gt;&lt;div&gt;&lt;picture&gt;&lt;source&gt;&lt;img&gt;","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759285","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":"Pressure-driven densification and connectivity in a CuZr metallic glass","authors":"Nicolas Amigo,&nbsp;Juan Cantos","doi":"10.1007/s00894-026-06719-2","DOIUrl":"10.1007/s00894-026-06719-2","url":null,"abstract":"<div><h3>Context</h3><p>Metallic glasses (MGs) exhibit exceptional strength, elasticity, and corrosion resistance due to their disordered atomic structure, with Cu–Zr alloys serving as widely studied model systems. External pressure can significantly modify glass formation, atomic packing, and mechanical response by altering short-range order (SRO), medium-range order (MRO), and the glass transition temperature. While previous studies have reported pressure-induced crystallization or reductions in icosahedral ordering at high pressures, the present work shows that moderate external pressures (&lt;10 GPa) enhance dense atomic packing without triggering crystallization. In particular, pressure increases the glass transition temperature and promotes the formation and interconnectivity of icosahedra-like structures, strengthening the amorphous backbone of the glass.</p><h3>Methods</h3><p>Molecular dynamics simulations were performed on a <span>(text {Cu}_{64}text {Zr}_{36})</span> metallic glass obtained by cooling the liquid under external pressures ranging from 0 to 10 GPa. Structural evolution was characterized using radial distribution functions, Voronoi polyhedra analysis, and network connectivity analysis. SRO was quantified through populations of icosahedra-like (solid-like), transition, and liquid-like polyhedra, revealing a pressure-induced increase in solid-like and transition polyhedra and a reduction in liquid-like environments. MRO was examined via 2-atom, 3-atom, and 4-atom connections and the interconnectivity of icosahedra-like networks, showing enhanced face-sharing connectivity and increased network cohesion at higher pressures. Elastic moduli were calculated from the stiffness tensor and were found to increase with pressure, consistent with the formation of denser atomic packings and a more mechanically stable glass structure.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147738648","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 structure-based virtual screening approach to identify novel anaplastic lymphoma kinase inhibitors","authors":"Kajal Sandhu,&nbsp;Sibasis Sahoo,&nbsp;S. Chockalingam","doi":"10.1007/s00894-026-06727-2","DOIUrl":"10.1007/s00894-026-06727-2","url":null,"abstract":"<div><h3>Context</h3><p>Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that plays a crucial role in cellular signaling and is implicated in several cancers, including anaplastic large cell lymphoma (ALCL), non-small cell lung cancer (NSCLC), and neuroblastoma. ALK's catalytic activity is driven by its intracellular kinase domain, which activates key signaling pathways, making it an important target for small-molecule inhibitors. Although FDA (Food and Drug Administration) approved inhibitors such as crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib have improved clinical outcomes, their efficacy is often challenged by resistance mechanisms, including secondary kinase domain mutations and activation of bypass pathways. As a step towards overcoming the challenges associated with the existing inhibitors, we conducted virtual screening of the ZINC database to discover novel and alternative compounds with potential ALK inhibitory activity. The top hits obtained following a three-tiered virtual screening process namely high throughput virtual screening, standard precision, and extra precision, were further analyzed using molecular dynamics simulations to evaluate the stability of ALK-small molecule complexes under physiological conditions. Free energy calculations and binding affinity prediction were conducted to estimate the binding affinities along with per-residue energy decomposition of the most stable complexes. Principal component analysis further revealed dominant motions in apo and ligand-bound ALK, underscoring the role of key residues in conformational changes and complex stabilization. This integrative computational approach identified ZINC97743494, ZINC55325417, and ZINC83408527 as promising ALK inhibitors with potential to improve therapeutic strategies for ALK-positive cancers.</p><h3>Method</h3><p>The ZINC12 library was processed using LigPrep to generate optimized 3D structures, followed by multi-tiered virtual screening against the ALK kinase domain (PDB: 2XP2), prepared using the Schrödinger Suite. MMGBSA (Molecular Mechanics/Generalized Born Surface Area) binding free energy calculations and ADME-based pharmacokinetic analyses were performed for the top hits. MD simulations were conducted using Desmond to evaluate complex stability. Binding free energies and per-residue contributions were computed using MMGBSA. Boltz-2 machine learning platform to predict KD values and the top three hits were validated using PCA and free energy landscape.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147738649","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":"Comparative investigation of uridine and Hachimoji RNA base interaction with single-walled carbon nanotube","authors":"Mashari Alangari","doi":"10.1007/s00894-026-06726-3","DOIUrl":"10.1007/s00894-026-06726-3","url":null,"abstract":"<div><h3>Context</h3><p>Single-walled carbon nanotubes (SWCNTs) are promising platforms for biosensing because their electronic properties are sensitive to molecular adsorption. While canonical nucleic acid bases have been extensively studied, little is known about how synthetic Hachimoji bases interact with nanotube surfaces. In this study, we investigate the adsorption of uridine (rU) and the Hachimoji base S (rS) on a finite (5,5) SWCNT fragment. The study aims to compare binding strength and electronic effects between canonical and synthetic bases within a finite gas-phase SWCNT model and to examine whether the two bases show distinguishable local adsorption behavior.</p><h3>Methods</h3><p>All geometries of the isolated molecules and the SWCNT+rU and SWCNT+rS complexes were fully optimized using density functional theory (DFT) with the PBEh-3c composite method in ORCA. The adsorption complexes were analyzed on an 8 Å hydrogen-terminated (5,5) SWCNT fragment, with the bases initially placed approximately parallel to the nanotube sidewall at ~ 3.1 Å. HOMO-LUMO gaps were calculated for each system: rU (~ 7.5 eV), rS (~ 7.7 eV), SWCNT (~ 3.21 eV), SWCNT + rU (~ 3.19 eV), and SWCNT + rS (~ 3.20 eV). Interaction energies of the optimized complexes were computed using the supermolecule approach, yielding − 0.43364 eV for SWCNT+rU and − 0.55405 eV for SWCNT + rS. Mulliken population analysis was performed to quantify fragment charge redistribution, showing only minor net charge transfer.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00894-026-06726-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147738520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}