Journal of Molecular Modeling最新文献

{"title":"Rational hybrid design and computational characterization of PA-Hyb1: a novel peptide inhibitor targeting the MexB efflux pump in Pseudomonas aeruginosa","authors":"Sekena H. Abdel-Aziem","doi":"10.1007/s00894-026-06929-8","DOIUrl":"10.1007/s00894-026-06929-8","url":null,"abstract":"<div><h3>Context</h3><p>The MexAB-OprM efflux pump is a primary driver of multidrug resistance in <i>Pseudomonas aeruginosa</i>. While antimicrobial peptides (AMPs) offer a promising alternative to small-molecule inhibitors, understanding their dynamic interactions with large, multi-domain membrane transporters like MexB requires rigorous computational modeling. Rational hybrid peptide design combined with physics-based Molecular Dynamics simulations provides a strategic pathway to optimize AMP efficacy and predict binding stability prior to experimental synthesis. Ten hybrid peptides were designed and screened in silico for toxicity and physicochemical properties. The lead candidate, PA-Hyb1, exhibited a stable α-helical conformation and favorable safety profiles. During extended MD simulations, PA-Hyb1 displayed structural flexibility, anchoring its hydrophobic N-terminus via persistent π-π stacking with Phe178/Phe610, while its cationic C-terminus dynamically scanned acidic vestibule residues. MM/PBSA calculations over the equilibrated trajectory (from 300 to 500 ns) yielded a binding enthalpy of -28.5 ± 2.4 kcal/mol. This interaction energy was significantly superior to levofloxacin (-14.2 ± 1.8 kcal/mol; <i>p</i> < 0.0001) and outperformed scrambled and parent fragment controls, closely approaching the rigid small-molecule inhibitor D13-9001 (-30.1 ± 1.8 kcal/mol), despite the inherent entropic penalty of peptide flexibility. The computational pipeline successfully identified PA-Hyb1 as a high-affinity, sequence-specific candidate for MexB inhibition, establishing a strong rationale for its in vitro synthesis and validation. These binding-mode findings were obtained in a DPPC/POPE bilayer used as a simplified membrane-mimetic system rather than the native Pseudomonas aeruginosa inner-membrane lipid composition (predominantly phosphatidylethanolamine, phosphatidylglycerol, and cardiolipin), and outer-membrane penetration by PA-Hyb1 was not evaluated; these limitations, together with a preliminary host-safety-only ADMET screen, temper the translational claims below and are discussed further in Sect. 4.1.</p><h3>Methods</h3><p>Ten hybrid peptides were designed by fusing functional motifs from Cecropin A, Magainin 2, and LL-37. Candidates were screened in silico for toxicity and physicochemical properties. The lead candidate, PA-Hyb1, was structurally modeled using PEP-FOLD4 and energy minimized under the CHARMM36m force field. Molecular docking (AutoDock Vina) targeted the distal binding pocket (Cavity C3) of MexB (PDB ID: 6IIA). To evaluate dynamic stability and binding thermodynamics, 500-ns all-atom Molecular Dynamics simulations were conducted in an explicit asymmetric DPPC/POPE lipid bilayer. Binding affinities were quantified using MM/PBSA free energy calculations and rigorously compared against a scrambled sequence control, parent fragments, levofloxacin, and the D13-9001 reference inhibitor.</p><h3>Graphical abstract</h3>\u0000<div><figur","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148927602","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":"Effect of defects on fracture and mechanical properties in Cu/Zr nanolayers","authors":"Hong-Anh Nguyen,&nbsp;Hoang-Giang Nguyen,&nbsp;Chung-Hao Hsu,&nbsp;Te-Hua Fang","doi":"10.1007/s00894-026-06941-y","DOIUrl":"10.1007/s00894-026-06941-y","url":null,"abstract":"<div><h3>Context</h3><p>In this work, the effects of strain rate, characteristics of defect on the tensile deformation and fracture behaviour of Cu/Zr nanolayers were systematically investigated. Increasing the strain rate enhances the Young’s modulus, tensile strength, effective fracture toughness and critical energy release rate by suppressing strain localization and delaying crack propagation. Crack geometry also governs fracture resistance, with circular cracks exhibiting the most uniform stress redistribution and the highest resistance to crack propagation, whereas other cracks promote localized deformation and preferential shear-band development. Atomistic analyses reveal that deformation is dominated by Shockley partial dislocations, FCC-to-HCP transformation in the Cu layers, amorphization of the Zr layers, and heterogeneous deformation across the Cu/Zr interfaces. The formation of an intermixed Cu–Zr transition region further facilitates stress transfer and contributes to interface strengthening.</p><h3>Methods</h3><p>The Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) was used to perform simulation. Atomic interactions in the Cu/Zr multilayer system were described using the embedded atom method (EAM) potential. Prior to tensile loading, the models were energy minimized and equilibrated under periodic boundary conditions. Uniaxial tensile deformation was applied at strain rates ranging from 10⁸ to 10¹⁰ s⁻¹. Structural evolution and deformation mechanisms were characterized using stress–strain analysis, Common Neighbour Analysis (CNA), the Dislocation Extraction Algorithm (DXA), atomic shear strain, von Mises stress, and dislocation density in the Open Visualization Tool (OVITO). The effective fracture toughness K_Ic and critical energy release rate G_c were evaluated based on linear elastic fracture mechanics using the maximum tensile stress and the characteristic crack dimension.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148927681","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":"Unveiling the effects of tautomerism, pH, and solvation on the UV/Vis spectrum of sulfapyridine: a joint theoretical and experimental study","authors":"José L. F. Santos,&nbsp;Lorena C. P. Sales,&nbsp;Fernanda L. Souza,&nbsp;Gabriel L. C. de Souza,&nbsp;Adrian E. Roitberg,&nbsp;Roberto L. A. Haiduke","doi":"10.1007/s00894-026-06933-y","DOIUrl":"10.1007/s00894-026-06933-y","url":null,"abstract":"<div><h3>Context</h3><p>Sulfapyridine (SPY) is a sulfonamide frequently detected as contaminant in aquatic environments, largely due to incomplete metabolism and its extensive use in livestock production and other anthropogenic activities. The spectroscopic properties of SPY are strongly influenced by prototropic tautomerism, pH conditions, and solvation effects. Herein, a joint theoretical–experimental study investigates the ultraviolet/visible (UV/Vis) electronic absorption spectra of SPY and its sulfonimide tautomer (TAUT) across different protonation states. Energetic analyses using a hybrid cluster-continuum (HCC) solvation approach reveal that TAUT forms predominate in aqueous solution. Hybrid solvation significantly lowers the tautomerization barriers (from 37.1 to 10.4 kcal.mol<span>(^{-1})</span> for neutral and from 35.4 to 8.6 kcal.mol<span>(^{-1})</span> for protonated forms), highlighting the catalytic role of the solvent. Theoretical data reproduce the main features of the experimental UV/Vis spectra, reinforcing that TAUT forms dominate in solution and exhibit characteristic absorption bands around 300 nm. These findings demonstrate that tautomeric equilibria and hybrid solvation are factors that strongly influence the spectroscopic properties of SPY in water and should be considered in studies involving sulfonamides, including biological interactions and photodegradation pathways.</p><h3>Methods</h3><p>Conformational analyses are carried out at the GFN2-xTB/GBSA level (CREST). Cluster structures from SOLVATOR, with posterior geometry optimizations and vibrational frequency calculations, are achieved at the GFN2-xTB/ALPB level in water (ORCA 6.0.1). DFT calculations are performed at the PBE-D3/cc-pVTZ/PCM level (Gaussian 09) for providing equilibrium geometries for the lowest-energy conformers. Improved single-point energies are retrieved from CAM-B3LYP-D3(BJ)/def2-QZVPP/SMD calculations, while TD-DFT data reached at the CAM-B3LYP/def2-TZVP/C-PCM level are employed for UV/Vis spectra simulation (ORCA 5.0.4).</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00894-026-06933-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148927601","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}

{"title":"Insights into the structural dynamics and free energy landscapes of Danio rerio RAB1A and RAB1B: a comparative molecular dynamics simulation approach","authors":"Bengü Sema Mutafoğlu,&nbsp;Özkan Danış,&nbsp;Özal Mutlu","doi":"10.1007/s00894-026-06938-7","DOIUrl":"10.1007/s00894-026-06938-7","url":null,"abstract":"<div><h3>Context</h3><p>RAB1A and RAB1B are highly conserved small GTPases that regulate endoplasmic reticulum-to-Golgi vesicle trafficking and are implicated in neurodegenerative diseases and cancer. Despite the increasing use of <i>Danio rerio</i> as a vertebrate model organism, the structural dynamics of zebrafish Rab1 isoforms remain uncharacterized. In this study, we performed the first comparative computational investigation of zebrafish RAB1A and RAB1B in their GDP- and GTP-bound conformational states. Sequence and structural analyses demonstrated a high degree of conservation between the two isoforms while revealing a characteristic Tyr-to-Phe substitution within the RAB1B Switch I region. Long-timescale molecular dynamics simulations showed that GDP-bound complexes exhibited greater structural stability, reduced residue fluctuations, and more compact conformations than the corresponding GTP-bound systems. These findings provide molecular insights into the functional dynamics of zebrafish Rab1 isoforms and support the use of <i>Danio rerio</i> as a translational model for Rab1-related biological processes and disease mechanisms.</p><h3>Methods</h3><p>The amino acid sequences of zebrafish RAB1A and RAB1B were analyzed using MUSCLE, PRATT, the Conserved Domain Database, and ExPASy ProtParam. Three-dimensional structures were generated by homology modeling with SWISS-MODEL using experimentally determined human Rab1 structures as templates and were validated using PROCHECK, ERRAT, Verify3D, ProSA-web, and QMEANDisCo. All-atom molecular dynamics simulations were performed in duplicate for 1 µs using GROMACS 2024.1 with the CHARMM36m force field and TIP3P explicit water model under periodic boundary conditions. Trajectory analyses included backbone root-mean-square deviation, root-mean-square fluctuation, radius of gyration, principal component analysis, dynamic cross-correlation matrix analysis, and free energy landscape calculations. Structural visualization and analyses were performed using PyMOL, Visual Molecular Dynamics (VMD), and the Bio3D package in R.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148927682","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 perfluorohexanone-based synergistic gas mixtures and mechanistic prediction of hydrogen fluoride formation pathways","authors":"Yinjiao Su,&nbsp;Bin Zheng,&nbsp;Dezheng Wang,&nbsp;Yinghui Li,&nbsp;Fei Wang","doi":"10.1007/s00894-026-06940-z","DOIUrl":"10.1007/s00894-026-06940-z","url":null,"abstract":"<div><h3>Context</h3><p>Perfluorohexanone (C₆F₁₂O, Novec 1230) has emerged as a leading halon alternative for fire suppression due to its near-zero ozone depletion potential and short atmospheric lifetime, yet its high-temperature decomposition can generate hydrogen fluoride (HF), posing secondary damage risks to protected assets—particularly in enclosed spaces housing cultural heritage artifacts where corrosive gas exposure must be minimized. Although the qualitative effects of inert dilution and an additional fluorinated component can be anticipated, formulation design requires quantitative information on the magnitude, timing, and nonlinearity of C₆F₁₂O conversion and HF-species formation across temperature, initial-density, and blend-ratio conditions. The present simulations were therefore designed as a controlled molecular-level comparison to identify formulations and conditions that warrant subsequent fire-suppression and HF-emission testing. Elevated temperature consistently accelerated C₆F₁₂O conversion and increased HF-species accumulation. N₂ substitution reduced the absolute number of identified HF species but delayed C₆F₁₂O conversion, whereas C₃HF₇ blending did not provide a consistent HF-reduction advantage at elevated temperatures. Among the investigated N₂ blending ratios, the C₆F₁₂O: N₂ = 1:3 system showed the lowest HF-species response and was therefore identified as a candidate for subsequent HF-mitigation testing rather than as an established optimum for fire-extinguishing operation.</p><h3>Methods</h3><p>This work employs a published ReaxFF parameterization to conduct reactive molecular dynamics simulations of the investigated C-H–O-F systems across the selected temperature, fixed-volume initial-density, and blend-ratio conditions. Three series of simulations were performed: (i) pure C₆F₁₂O as the baseline reference, (ii) C₆F₁₂O blended with N₂ to quantify the system-level effect of inert substitution, and (iii) C₆F₁₂O blended with C₃HF₇ to examine the effect of a reactive hydrogen- and fluorine-containing partner. Across the study, five temperatures (1400–3000 K) and several fixed-volume density conditions corresponding to nominal initial-pressure labels of 0.1–0.3 MPa were examined; multiple blend ratios were additionally considered for the N₂- and C₃HF₇-containing systems. The temporal evolution of intact perfluorohexanone, representative fragment populations, and identified HF species was compared across the investigated conditions to distinguish parent-molecule conversion from subsequent fluorine redistribution and HF formation.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148927606","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":"Plasmon hybridization and magnetic-permeability-dependent optical absorption in (mathrm{Fe_3O_4})-Cs core–shell nanostructures","authors":"Sarthak Gupta,&nbsp;Geeta Rani,&nbsp;Sanjeev Kumar,&nbsp;P. Arun,&nbsp;Kuldeep Kumar","doi":"10.1007/s00894-026-06948-5","DOIUrl":"10.1007/s00894-026-06948-5","url":null,"abstract":"&lt;p&gt;Magneto-plasmonic core–shell nanostructures provide a versatile platform for tailoring optical absorption through coupled magnetic and plasmonic interactions. In this work, the optical absorption properties of &lt;span&gt;(mathrm{Fe_3O_4})&lt;/span&gt;–Cs core–shell nanostructures embedded in alkali halide matrices (CsCl, CsBr, and CsI) are theoretically investigated using Maxwell–Garnett effective medium theory combined with frequency-dependent dielectric and magnetic responses. Two configurations are analyzed: (i) &lt;span&gt;(mathrm{Fe_3O_4})&lt;/span&gt; core–Cs shell (Model A) and (ii) Cs core–&lt;span&gt;(mathrm{Fe_3O_4})&lt;/span&gt; shell (Model B). The absorption spectra are investigated as functions of core–shell volume parameter, host dielectric constant, and nanoparticle filling factor. Model A exhibits two hybridized plasmon resonances arising from coupling between the inner &lt;span&gt;(mathrm{Fe_3O_4})&lt;/span&gt;–Cs and outer Cs–host interfaces, while Model B shows a single broadened resonance dominated by the Cs core. Increasing host dielectric constant produces pronounced red shifts, whereas increasing filling factor primarily enhances absorption intensity with minimal change in resonance wavelength. Simulations further show that increasing the magnetic permeability of the &lt;span&gt;(mathrm{Fe_3O_4})&lt;/span&gt; shell enhances magnetic damping, resulting in resonance broadening and reduced plasmon coherence. The results demonstrate that &lt;span&gt;(mathrm{Fe_3O_4})&lt;/span&gt;–Cs nanostructures exhibit tunable magneto-plasmonic absorption characteristics that may be useful for dielectric-environment-sensitive photonic and sensing applications. The calculated optical response suggests that &lt;span&gt;(mathrm{Fe_3O_4})&lt;/span&gt;/Cs core-shell structures may be of interest for future magneto-plasmonic and optical sensing studies.&lt;/p&gt;&lt;p&gt;Magneto-plasmonic core–shell nanostructures enable tunable optical absorption via coupled magnetic and plasmonic interactions, which is relevant for the design of dielectric-environment-sensitive photonic devices and refractive-index-based sensors. The effects of magnetic damping on the optical response were systematically investigated, revealing resonance broadening, reduced plasmonic coherence, and the emergence of weak Fano-type spectral asymmetry.&lt;/p&gt;&lt;p&gt;The optical properties were modeled within the quasistatic approximation using Maxwell–Garnett effective medium theory combined with frequency-dependent dielectric functions (Drude model for Cs) and constant magnetic permeability for &lt;span&gt;(mathrm{Fe_3O_4})&lt;/span&gt;. Effective permittivity and permeability of the composite were calculated for varying core–shell volume parameter (&lt;span&gt;(beta )&lt;/span&gt;), host dielectric constant (&lt;span&gt;(epsilon _{h})&lt;/span&gt;), filling factor (F), and magnetic permeability (&lt;span&gt;(mu )&lt;/span&gt;). Absorption spectra were derived from the imaginary part of the effective refractive index. Python 3.13 was used to implement the numerical simulations and optical modeling of the core–shell nanostruc","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917865","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":"Accurate prediction of UV absorption in zirconia–alumina mixed oxide (ZrAl4O8) via GW–BSE calculations","authors":"Alexandre B. Rocha,&nbsp;Angela S. Rocha","doi":"10.1007/s00894-026-06939-6","DOIUrl":"10.1007/s00894-026-06939-6","url":null,"abstract":"<div><h3>Context</h3><p>Zirconia is a technologically relevant material widely employed in catalysis owing to its thermal stability, acid–base surface properties, and optical response, enabling applications both as a solid acid catalyst and as a photocatalytic material. Even so, the relatively low specific surface area of bulk zirconia may limit its catalytic performance, making supported systems and mixed oxides attractive alternatives for enhancing dispersion and surface accessibility. Among these, zirconia–alumina mixed oxides have attracted significant attention because of the strong interfacial interactions established between both phases, which may involve a migration of Zr⁴⁺ species into the subsurface region of alumina, leading to the formation of structurally stable mixed oxide domains. This behavior has been associated with modifications in the electronic structure and surface reactivity of the material. In the present work, the UV absorption spectrum of the mixed oxide was calculated, and reasonable agreement was achieved with the measured gap and spectrum, reinforcing the existence of the mixed oxide. The bandgap was determined as 6.47 eV, close to the experimental values, and the simulated spectrum shows good agreement with the experimental profile.</p><h3>Methods</h3><p>The geometry of the mixed oxide was optimized with and without constraint at the DFT/PBE level with periodic boundary conditions, a plane-wave basis set for valence electrons, and projected augmented waves (PAW) to treat core electrons. Excited-state optical properties were evaluated by solving the Bethe–Salpeter equation (BSE) on top of GW quasiparticle energies, allowing an accurate description of electron–hole interactions and optical transitions. All calculations were done in VASP software.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00894-026-06939-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917859","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}

{"title":"Influence of rare-gas tagging on the structure and vibrational properties of the hydroxymethyl cation [CH₂OH]⁺","authors":"Soran Khwakaram Ibrahim,&nbsp;Media Ismael Sulaiman","doi":"10.1007/s00894-026-06946-7","DOIUrl":"10.1007/s00894-026-06946-7","url":null,"abstract":"<div><h3>Context</h3><p>Non-covalent interactions between the hydroxymethyl cation [CH₂OH]⁺ and three rare-gas messenger atoms (helium, neon, and argon) are investigated to understand their effects on the structure and vibrational properties. The calculations reveal that three stable binding motifs (the O-bound, H-bound, and face-on isomers) are predicted; the O-bound isomer is the global minimum in each rare-gas series. The calculations indicated that the interaction strength increases with polarizability. Vibrational analysis demonstrates a clear mode- and site-dependent behavior, where the O–H bond exhibits a significant red shift in the Ar-tagged complex, while the C–H stretching modes exhibit both red and blue shifts depending on the binding motifs. The calculations confirmed that rare-gas atoms exhibit measurable perturbation, with He acting as the least intrusive messenger atom. The study provides important insights into the interpretation of infrared photodissociation spectra of molecular cations.</p><h3>Methods</h3><p>Ab initio calculations were performed at second-order Møller–Plesset perturbation theory (MP2) with the aug-cc-pVTZ basis set. All of the optimized structures, vibrational frequencies, natural bond orbital analyses, and interaction energies are calculated using the same theory and basis sets, while CCSD(T) is used only for the single-point energy at the same basis sets.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00894-026-06946-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918039","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}

{"title":"Molecular modeling design of antitrypanosomal pyrazolone derivatives targeting Chagas disease: QSAR, docking, molecular dynamics and free energy calculations","authors":"Karen Karla F. Sousa,&nbsp;Ana Beatriz S. Barbosa,&nbsp;Fábio José B. Cardoso,&nbsp;José Rogério A. Silva,&nbsp;Fábio A. Molfetta","doi":"10.1007/s00894-026-06923-0","DOIUrl":"10.1007/s00894-026-06923-0","url":null,"abstract":"<div><h3>Context</h3><p>Chagas disease, caused by <i>T. cruzi</i>, remains a neglected tropical disease with limited therapeutic options, underscoring the urgent need for novel antitrypanosomal agents. A computer-aided drug design (CADD) protocol was applied to investigate pyrazolone derivatives with reported antitrypanosomal activity and their putative interaction with cruzain (Cz), a cysteine protease essential for parasite survival. A 2D-QSAR model built from a curated set of 33 phenyl-dihydropyrazolone derivatives guided the design of four new candidates (LMM1–LMM4), which showed intermediate predicted antitrypanosomal activity within the chemical space of the original pyrazolone series. Molecular docking identified favorable binding within the Cz active site, with contacts at residues Ser61, Gly66, and Leu67. MD simulations indicated overall structural stability of the protein–ligand complexes and revealed ligand-dependent conformational behavior within the Cz binding site. MM/GBSA calculations suggested that van der Waals interactions are major contributors to the computed binding energies; however, the MM/GBSA ranking did not fully reproduce the phenotypic antitrypanosomal activity trend. Per-residue decomposition and free energy landscape analyses were therefore interpreted qualitatively, suggesting that contacts with S2/S3 subsite residues and conformational adaptability may contribute to Cz recognition but do not, alone, explain whole-cell potency. These findings support pyrazolones as antitrypanosomal scaffolds and provide structural hypotheses for future experimental validation against Cz.</p><h3>Methods</h3><p>Molecular geometries were optimized at the PM6 level (MOPAC2016); descriptors were calculated with ChemDes and UseGalaxy, selected via OPS and a genetic algorithm (QSARINS), and the QSAR model was built using PLS regression (QSAR modeling software). Molecular docking was performed with GOLD, FITTED, and AutoDock Vina 1.2.3 against Cz (PDB: 3KKU). ADMET properties were predicted using OSIRIS Property Explorer, SwissADME, and ADMET-AI. Partial atomic charges were derived at the HF/6-31G* level with RESP fitting (Gaussian 09); MD simulations (3 × 250 ns per system) were run with AMBER20 using GAFF/ff14SB force fields and TIP3P solvent. Binding free energies were calculated by MM/GBSA (MMPBSA.py).</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00894-026-06923-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917967","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}

{"title":"First-principles calculations for the adsorption of lithium sulfide by zinc oxide","authors":"Jin-Ke Wei,&nbsp;Zhi-Xin Bai,&nbsp; Wei-Zeng,&nbsp;Zheng-Tang Liu,&nbsp;Cheng-Lu Jiang","doi":"10.1007/s00894-026-06935-w","DOIUrl":"10.1007/s00894-026-06935-w","url":null,"abstract":"<div><h3>Context</h3><p>Lithium‒sulfur batteries (LSBs) are regarded as next-generation energy storage technologies owing to their high energy density; however, their practical application is constrained by the shuttle effect of lithium polysulfides (LiPSs), which leads to capacity degradation and safety concerns. This work focuses on the adsorption mechanism of Li₂S on ZnO and investigates the microscopic mechanism by which ZnO suppresses the shuttle effect through first-principles calculations. The results demonstrate that the adsorption energy of a Li₂S molecule on the ZnO (100) facet is negative (−1.67 eV), which is thermodynamically more favorable than that on the (111) facet (1.73 eV). The Li–O ionic bonds and S–Zn covalent bonds formed between the (111) facet and the Li₂S molecule exhibit stronger coupling than those on the (100) facet, resulting in stronger overall interfacial electronic interactions. Nevertheless, the deformation magnitude of the Li–S bond on the (111) facet (9%–14%) exceeds that on the (100) facet (less than 5%). The (100) facet achieves energetically superior stable adsorption through weak bonding and low deformation, whereas the (111) facet, despite stronger bonding, has a deformation energy that surpasses the energy released by bond formation, rendering it a thermodynamically metastable configuration. Evidently, ZnO strongly adsorbs Li₂S—the final product of the shuttle effect—thereby suppressing the shuttle effect to a certain extent.</p><h3>Methods</h3><p>In this study, first-principles calculations were performed via the Materials Studio software via density functional theory (DFT) via the generalized gradient approximation (GGA) with the PBE functional and the GGA-PBE + U approach. Ultrasoft pseudopotentials were employed to balance computational efficiency and accuracy. Crystal models of zinc oxide (ZnO) and Li₂S were constructed via the CASTEP code. The nonpolar (100) facet and polar (111) facet of ZnO were selected for Li₂S molecule adsorption, followed by structural optimization. The adsorption energy, electronic band structure, partial density of states (PDOS), charge density, Mulliken charge population, and chemical bond lengths were subsequently calculated.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00894-026-06935-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917949","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}