Journal of molecular graphics & modelling最新文献

{"title":"DFT insights into synergistic interactions and ORR mechanisms of BN-supported dual-atom catalysts","authors":"Elaheh Ahmadi,&nbsp;Maryam Anafcheh,&nbsp;Soode Amigh","doi":"10.1016/j.jmgm.2025.109274","DOIUrl":"10.1016/j.jmgm.2025.109274","url":null,"abstract":"<div><div>The intrinsically slow kinetics of the oxygen reduction reaction (ORR) remains a major hurdle to the practical use of fuel cells. In this regard, we conducted a systematic theoretical exploration of ten dual-atom transition metal catalysts (Fe, Co, Ni, and Cu) supported on defective boron nitride to clarify the structure-activity relationship governing ORR performance. The evaluation of formation energies, stability, electronic structure, and catalytic properties indicates that dual-metal incorporation efficiently narrows the band gap of pristine BN and adjusts the d-band center, optimizing the adsorption and activation of oxygenated intermediates. Among the investigated catalysts, 2Cu-BN, CoCu-BN, and CuNi-BN have the lowest theoretical overpotentials of 0.64 V, 0.67 V, and 0.70 V, respectively. The 2Cu-BN catalyst exhibits a stable end-bridge adsorption configuration of O₂, and the CoCu-BN and CuNi-BN catalysts show stable end-on adsorption configurations of O₂ on top of cobalt and nickel centers, respectively. For the majority of the systems, the potential-determining step (PDS) is the transition of ∗OH → H₂O, but the 2Cu-BN catalyst exhibits an alternate path with ∗O₂ → ∗OOH as the PDS. Scaling relations and volcano plot analyses also confirm ΔG_∗OH as a reliable descriptor of the ORR activity. Overall, these findings highlight the potential of 2D-BN-supported dual-atom catalysts as a promising next-generation fuel cell alternative that can substitute platinum efficiently and cost-effectively.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"143 ","pages":"Article 109274"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breaking resistance with machine and deep learning: A computational intelligence hunt for AmvR (TetR) inhibitors in Acinetobacter baumannii","authors":"Yahya A. Almutawif ,&nbsp;Saad Amin ,&nbsp;Sajjad Ahmad ,&nbsp;Kalsoom Khan ,&nbsp;Asad Ullah ,&nbsp;Abu Nasar Siddique ,&nbsp;Faisal Ahmad","doi":"10.1016/j.jmgm.2025.109261","DOIUrl":"10.1016/j.jmgm.2025.109261","url":null,"abstract":"<div><div>Multidrug-resistant <em>Acinetobacter baumannii</em> infections have driven the development of innovative therapeutic approaches to address global challenges. The present study reported that the protein belonging to the TetR family regulator AmvR from <em>A. baumannii</em> is bound to spermidine. Here, quantitative structure-activity relationship (QSAR) models developed from a ChEMBL dataset were used to perform an initial screening of a library of 10,860 natural chemical compounds, along with their reported minimum inhibitory concentration (MIC) scores. Machine learning models, including RF, SVM, KNN, and XGBoost, were implemented for compound classification. An RF model was selected that achieved a 96 % accuracy score on the test set. A deep learning model, CNN, was built, and a structure-based virtual screening approach was applied against <em>A. baumann</em>ii to assess how similar these molecules are to drug likeness. In silico pharmacokinetic analysis was performed for the top candidates, including binding energy evaluation of protein-ligand docking with scores of −10.6 kcal/mol, −10.4 kcal/mol, and a control with −6 kcal/mol. Absorption, distribution, metabolism, and excretion (ADME) properties for CHEMBL-560977, CHEMBL-551116, and the control complex were also noted. Additionally, the binding mechanism was elucidated through molecular dynamics simulations over 500 ns, with binding free energy analysis (MMGBSA/PBSA) showing results of −120.55 kcal/mol, −94.99 kcal/mol, and −90.65 kcal/mol. Dynamic cross-correlation matrix (DCCM), radial distribution function (RDF), and hydrogen bonding (H-bonds) analyses were conducted, along with principal component analysis (PCA) and free energy landscape (FEL) clustering for the selected complexes. Secondary structure analysis and salt bridge assessments indicated that the newly discovered compounds are more promising than the currently available drugs. According to all docking and MD simulation results, the ligand-bound protein exhibits promising and stable behavior. Lastly, the selected compounds are recommended for further experimental studies and could serve as potent inhibitors of <em>A. baumannii</em> infection.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"143 ","pages":"Article 109261"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theoretical calculations of monolayer PtS2 as a drug delivery carrier for ursolic acid","authors":"Qinghua Yang ,&nbsp;Maodong Guo ,&nbsp;Xiao Zhu","doi":"10.1016/j.jmgm.2025.109234","DOIUrl":"10.1016/j.jmgm.2025.109234","url":null,"abstract":"<div><div>Ursolic acid (UA) exhibits anti-inflammatory and anti-tumor properties. Developing a nanodrug delivery system for UA can improve its bioavailability. Transition metal sulfides, owing to their distinctive physicochemical characteristics, have emerged as the predominant two-dimensional nanostructures utilized in the advancement of nanodrug delivery systems in recent years. This study employs first-principles calculations to assess the viability of monolayer PtS₂ as a carrier for UA. The results indicate that monolayer PtS₂ exhibits structural stability as a UA carrier, with an adsorption energy of −3.84 eV. Mulliken charge analysis reveals that UA donates 0.34 |e| to PtS₂. Additionally, the application of strain induces a redshift in the optical absorption peak of monolayer PtS₂, thereby enhancing its optical absorption capabilities. Furthermore, monolayer PtS₂ displays favorable temperature-controlled release properties when utilized as a delivery vehicle for Ursolic acid. These results offer theoretical insights that could inform the development of innovative drug carriers and significantly contribute to the treatment of inflammatory bowel disease.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"143 ","pages":"Article 109234"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145617525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational investigation of high Curie temperature, magnetic anisotropy and optical properties of new Zr based half-Heusler compounds","authors":"R. Rajeswara Palanichamy ,&nbsp;A. Amudhavalli ,&nbsp;R. Meenakshi ,&nbsp;T.M. Chithresh ,&nbsp;M. Manikandan ,&nbsp;K. Iyakutti ,&nbsp;Y. Kawazoe","doi":"10.1016/j.jmgm.2025.109248","DOIUrl":"10.1016/j.jmgm.2025.109248","url":null,"abstract":"<div><div>First-principles calculations based on the density functional theory (DFT) are employed to study the structural, electronic, magnetic, optical, and thermal properties of new Zr based half- Heusler compounds with α, β and γ phases. The most stable state is predicted as ferromagnetic α-phase. Electronic structure predicted the half metallic property and indirect band gap nature of the compounds. The magnetic moment around 1μ_B obeys the Slater-Pauling rule. The spin polarization at the Fermi level is 100 % which also supports the half metallic behavior. The high Curie temperature values 342.7 K, 1082.7 K and 835.3 K of these half-Heusler alloys make them strong ferromagnets. The high value of dielectric function leads to better polarization, stability and energy storage. The dielectric constant values of ZrFeAs, ZrFeSb and ZrFeBi are found to be 19.4, 18.6 and 18.1 respectively. The absence of negative frequency modes in phonon dispersion curve suggests that these alloys are dynamically stable. The zero-point energy values of ZrFeAs, ZrFeSb and ZrFeBi are 8.4 kJ/mol, 8.06 kJ/mol and 6.79 kJ/mol respectively.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"143 ","pages":"Article 109248"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CG-COA: a coarse-grained cubic orientation approach for systematic protein-protein docking validation","authors":"Zekeriya Duzgun ,&nbsp;Zuhal Eroglu","doi":"10.1016/j.jmgm.2025.109245","DOIUrl":"10.1016/j.jmgm.2025.109245","url":null,"abstract":"<div><div>Traditional protein-protein docking algorithms face significant limitations when handling flexible protein systems, particularly where conformational flexibility plays crucial roles in binding specificity. This study developed and validated a Coarse-Grained Cubic Orientation Approach (CG-COA) that systematically samples six cubic orientations combined with coarse-grained molecular dynamics simulations and MM/PBSA free energy calculations. As a local docking approach, CG-COA requires prior knowledge of putative bioactive surfaces and focuses computational resources on biologically relevant binding orientations.</div><div>The methodology was validated using six protein complexes: four core systems (PDB codes: <span><span>2HD5</span><svg><path></path></svg></span>, <span><span>1MIM</span><svg><path></path></svg></span>, <span><span>3QML</span><svg><path></path></svg></span>, <span><span>2MWS</span><svg><path></path></svg></span>) representing diverse binding mechanisms, plus two extreme scenarios (2MZD: intrinsically disordered proteins; 2QCS-1RGS: large conformational changes). Benchmark comparisons against established docking methods (ZDOCK and ClusPro) evaluated relative performance across different system types.</div><div>Results demonstrated robust performance with overall AUROC of 0.94, achieving F-scores up to 1.00 for well-defined systems. Benchmark analysis revealed system-dependent performance: significant advantages for flexible systems (3QML: 3.7–5.1-fold improvement over rigid-body methods) but inferior performance for rigid interfaces (2HD5: outperformed by conventional approaches). Extreme docking scenarios revealed clear method limitations with poor structural accuracy (RMSDs &gt;13 Å), defining important applicability boundaries. The approach correctly diagnosed inherently flexible systems (2MWS) by not converging to single conformations.</div><div>CG-COA addresses specific limitations of conventional protein-protein docking methods for systems with moderate conformational flexibility while clearly defining applicability boundaries. The methodology is unsuitable for extensive structural rearrangements or intrinsically disordered regions. The dual capability to identify native binding modes and diagnose flexibility provides valuable guidance for protein interaction studies.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"143 ","pages":"Article 109245"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145654704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-principles design of a Mg-porphyrin nanoring sensor via dipole moment and dispersion energy engineering for high-sensitivity detection of hazardous industrial gases","authors":"Sattar Arshadi ,&nbsp;Mina Salary ,&nbsp;Omid Marvi","doi":"10.1016/j.jmgm.2025.109233","DOIUrl":"10.1016/j.jmgm.2025.109233","url":null,"abstract":"<div><div>This study employs density functional theory (DFT) with Grimme's D3-BJ dispersion correction to investigate the adsorption of six hazardous industrial gases (HI_Gas) including cyanogen chloride (CNCl), formaldehyde (CH₂O), cyanogen (C₂N₂), hydrogen cyanide (HCN), dichloroacetylene (C₂Cl₂), and phosgene (COCl₂) on a magnesium-porphyrin nanoring sensor (NR₄P₄Mg₄). The interactions are characterized as physical and reversible, with BSSE corrected adsorption energies ranging from −1.90 to −18.36 kcal/mol. Gas adsorption induces a significant band gap increase of approximately 122 %, substantially reducing electrical conductivity, while maintaining adsorption distances of 2.16–3.09 Å consistent with physisorption. The calculated recovery times spanning picoseconds to microseconds indicate rapid adsorption-desorption cycles. Electronic structure analysis through Natural Bond Orbital (NBO) and Frontier Molecular Orbital (FMO) calculations reveals consistent electron transfer from gas molecule HOMOs to the nanoring's LUMO. The presence of four distinct adsorption sites enables saturation-free detection of HI_Gas, with demonstrated resilience against atmospheric interference from nitrogen and humidity.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"143 ","pages":"Article 109233"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145610622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico identification of food-grade cooling compounds targeting TRPM8 and TRPA1: A dual-target approach","authors":"Zhongwei Zhang ,&nbsp;Jun Wang ,&nbsp;Yu Liu ,&nbsp;Xiangyu Li ,&nbsp;Hao Shu ,&nbsp;Jideng Chu ,&nbsp;Zhangqi Chai ,&nbsp;Junsong Xiao ,&nbsp;Guangwen Ma ,&nbsp;Hua Wu","doi":"10.1016/j.jmgm.2025.109257","DOIUrl":"10.1016/j.jmgm.2025.109257","url":null,"abstract":"<div><h3>Background</h3><div>Oral mucosa is susceptible to pathological changes, including burning sensation, erythema, and inflammation, when exposed to thermal, mechanical, or chemical stimuli. These changes significantly impact oral comfort and health. To address the need for oral cooling agents, this study targets both TRPM8 and TRPA1 channels. We established a “computation-screening-validation” system using homology modeling and virtual screening to identify potential cooling agents from 555 natural flavorings approved for food use in China.</div></div><div><h3>Results</h3><div>High-quality homology models of TRPM8 and TRPA1 were constructed. Multi-stage virtual screening was then performed using molecular docking. This process incorporated pharmacokinetic properties, key physicochemical properties (water solubility and lipophilicity), and Protox3.0 toxicity predictions. The structural stability of promising ligand-target complexes was further evaluated via molecular dynamics simulations. The screening identified α-Terpineol, cis-Jasmone, and Benzyl Salicylate as promising candidates. These compounds demonstrated superior predicted binding affinities for both targets compared to other screened compounds and favorable safety profiles. Molecular dynamics simulations confirmed stable binding and structural compactness of these compounds within the TRPM8 and TRPA1 binding sites.</div></div><div><h3>Conclusions</h3><div>This dual-target in silico approach offers an efficient, systematic way to identify safe and effective cooling agents. It provides valuable insights for the development of temperature-sensing modulators by highlighting compounds that can simultaneously activate TRPM8 and TRPA1.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"143 ","pages":"Article 109257"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145763395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning-guided repurposing of FDA-approved quinolones as dual cholinesterase inhibitors: A multi-level docking, molecular dynamics, DFT, and SHAP-based analysis","authors":"Cüneyt Türkeş","doi":"10.1016/j.jmgm.2025.109259","DOIUrl":"10.1016/j.jmgm.2025.109259","url":null,"abstract":"<div><div>Alzheimer's disease (AD) involves progressive cholinergic degeneration, with acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) playing key enzymatic roles in its pathology. In this study, we computationally repurposed four FDA-approved quinolone antibiotics, Norfloxacin, Sparfloxacin, Gatifloxacin, and Nalidixic acid, as potential dual-site cholinesterase (ChE) inhibitors using a hybrid <em>in vitro</em>/<em>in silico</em> workflow. Enzyme inhibition assays identified Norfloxacin as the most potent AChE inhibitor (<em>K</em>_I = 1.08 μM), while all compounds displayed non-competitive inhibition toward BChE. Molecular docking and MM-GBSA binding free energy analyses revealed key interactions within the catalytic gorge of AChE, supported by hydrogen bonding with Phe295 and Arg296, as well as π–π contacts with Tyr124. Density functional theory computations highlighted the influence of frontier orbital distribution on binding affinity, particularly for Norfloxacin and Sparfloxacin. An explicit-solvent molecular dynamics simulation of the AChE–Norfloxacin complex further confirmed the stability of the docking-derived binding mode over 100 ns. In an exploratory fashion, SHAP-based machine learning models were applied to a descriptor set derived from QikProp, SwissADME, and Jaguar outputs, suggesting that BBB-related indices and HOMO energy contribute to AChE inhibition, whereas the energy gap is more relevant for BChE; these trends, however, are constrained by the small four-compound dataset and should be regarded as hypothesis-generating. <em>In silico</em> ADME/Tox profiling indicated favorable oral drug-like properties, low predicted CYP450 inhibition liabilities, and physicochemical profiles compatible with CNS-oriented optimization, although passive BBB permeability was not predicted to be high. Finally, systems-level enrichment (STRING, GeneCards) provided a qualitative network context linking ACHE and BCHE to neurodegeneration. Together, these data position Norfloxacin and Sparfloxacin as computationally prioritised candidates whose ChE-related repurposing potential warrants further validation in dedicated cellular and <em>in vivo</em> models.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"143 ","pages":"Article 109259"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of chain length on the structure of aqueous surfactin solutions: Molecular dynamics studies","authors":"Loknath Patro,&nbsp;B.L. Bhargava","doi":"10.1016/j.jmgm.2025.109252","DOIUrl":"10.1016/j.jmgm.2025.109252","url":null,"abstract":"<div><div>Surfactin, a highly effective biosurfactant synthesized by various strains of Bacillus subtilis, exhibits remarkable biological and physicochemical properties. Molecular dynamics simulations highlight the influence of hydrocarbon chain length on the micellar structure, aggregation behavior, hydrogen bonding patterns, and secondary structure of surfactin molecules. The findings reveal that the aggregates adopt an increasingly spherical shape as the hydrocarbon chain length increases. The aggregation number of surfactin molecules also increases with longer chain lengths, indicating enhanced clustering tendencies. In the peptide ring, the occurrence of <span><math><mi>γ</mi></math></span>-turn, identified by the intramolecular hydrogen bond between Leu2 – Val4 residues, decreases with increasing chain length. The <span><math><mi>β</mi></math></span>-turn, identified by hydrogen bond between Leu2–Asp5 does not exhibit a clear trend, though the maximum occurrence probability is observed in systems with surfactin having longer alkyl tail. The surface tension of surfactin solutions increases with chain length due to lower coverage of the surface in case of surfactins with longer tails due to the tilted orientation of their hydrophobic tails, which limits efficient packing.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"143 ","pages":"Article 109252"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145734019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of potential inhibitors of Mycobacterium tuberculosis PknA using integrative molecular modeling approaches","authors":"Gonzalo A. Olivera-Gonzales ,&nbsp;Alicia Arica-Sosa ,&nbsp;Leonardo J. Monroy-Cruz ,&nbsp;Cintia A. Menéndez ,&nbsp;Miguel Quiliano","doi":"10.1016/j.jmgm.2025.109244","DOIUrl":"10.1016/j.jmgm.2025.109244","url":null,"abstract":"<div><div>Tuberculosis (TB) is one of the leading causes of mortality worldwide. Although it is considered a curable disease, the emergence of strains resistant to conventional treatments has rendered it a significant public health problem. Therefore, it is necessary to identify new therapeutic targets to combat this disease. The serine/threonine protein kinase A (PknA) has gained relevance due to its essential role in cell wall synthesis and the growth of <em>Mycobacterium tuberculosis</em> (<em>Mtb</em>). In the present study, an integrative molecular modeling approach was developed for the screening of libraries containing 1 581 625 compounds to identify potential PknA inhibitors. Pharmacophore-based virtual screening, followed by molecular docking, steered molecular dynamics, and binding free energy calculations have identified compound CHEMBL552033 as a promising hit compound. In addition, <em>in silico</em> ADME profiling, pharmacophore-based toxicity assessment, and kinase selectivity screening were performed to evaluate overall suitability as a promising hit. Molecular dynamics simulations of the PknA–CHEMBL552033 complex demonstrated the stability of the interaction, and the binding free energy values obtained by MM-GBSA (−49.54 ± 7.08 kcal/mol) and LIE-D method (−7.01 ± 1.26 kcal/mol) emphasize the potential of CHEMBL552033 as a potential inhibitor for the development of novel anti-TB therapies.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"143 ","pages":"Article 109244"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}