Journal of molecular graphics & modelling最新文献

{"title":"ClathPLM: Deep multi-view feature extraction with CNN and attention enhances clathrin protein identification","authors":"Shuxin Song,&nbsp;Yusen Su,&nbsp;Qingyang Guo,&nbsp;Taigang Liu","doi":"10.1016/j.jmgm.2026.109307","DOIUrl":"10.1016/j.jmgm.2026.109307","url":null,"abstract":"<div><div>Clathrin is a key structural protein in intracellular vesicle transport, mainly mediating clathrin-mediated endocytosis (CME) through trimeric assembly. Its functional abnormalities are closely associated with various diseases, including neurodegenerative disorders, tumor metastasis, and immune system dysregulation. Traditional experimental methods for identifying the presence of Clathrin have limitations such as high cost and time consumption. Therefore, it is particularly urgent to develop efficient and reliable computational methods to assist in Clathrin recognition. In this study, we propose a model named ClathPLM, which integrates sequence embeddings from three pre-trained protein language models (PPLMs), i.e., ProtT5, ProtBert, and ESM-3, and performs deep representation learning on each feature through an independent branch composed of a convolutional neural network (CNN) and a multi-head Attention (MHA) mechanism, finally fusing the representations of the three views to accomplish the classification task. To validate the effectiveness of this design, we further examined variants of the fusion strategy and attention mechanism. Evaluation results show that ClathPLM demonstrates excellent overall classification performance and robustness, surpassing current state-of-the-art methods. Moreover, the model performs strongly on an additional case-study dataset and shows good scalability on an extra vesicular transport proteins (VTPs) dataset. We anticipate that ClathPLM may contribute to a deeper understanding of the role of Clathrin in cellular regulation and disease mechanisms, and facilitate future biological studies as well as potential clinical applications.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"144 ","pages":"Article 109307"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046802","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":"Exploring traditional Chinese medicine for antiviral drug discovery: A computational approach to combat human metapneumovirus (HMPV)","authors":"Amit Dubey ,&nbsp;Manish Kumar ,&nbsp;Aisha Tufail ,&nbsp;Vivek Dhar Dwivedi","doi":"10.1016/j.jmgm.2026.109290","DOIUrl":"10.1016/j.jmgm.2026.109290","url":null,"abstract":"<div><div>Human metapneumovirus (HMPV) remains a major respiratory pathogen without approved antivirals, highlighting the urgent need for novel therapeutics. This study implemented an integrative computational pipeline combining virtual screening, molecular docking, 2 μs molecular dynamics (MD) simulations, density functional theory (DFT), pharmacophore modeling, and ADMET profiling to identify potent HMPV inhibitors from Traditional Chinese Medicine. Among 180 screened phytoconstituents, <strong>glycyrrhizin (–9.3 kcal mol⁻¹)</strong>, <strong>hesperidin (–9.1 kcal mol⁻¹)</strong>, and <strong>saikosaponins (–9.0 kcal mol⁻¹)</strong> exhibited strong binding affinities toward the HMPV matrix protein (<strong>PDB ID: 5WB0</strong>). Extended MD simulations confirmed complex stability with <strong>RMSD 0.17</strong>–<strong>0.22 nm</strong>, average of <strong>3</strong>–<strong>5 persistent H-bonds</strong>, and <strong>DCCM correlation coefficient = 0.86</strong> for glycyrrhizin. <strong>MM-PBSA</strong> binding free energies (ΔG_bind) of <strong>–46.2 ± 2.5</strong>, <strong>–44.7 ± 2.8</strong>, and <strong>–43.9 ± 2.2 kJ mol⁻¹</strong> for glycyrrhizin, hesperidin, and oseltamivir respectively, validated strong and stable interactions. <strong>DFT</strong> results indicated favorable electronic reactivity (HOMO–LUMO gap = 3.86 eV; electrophilicity = 2.74 eV), enhancing ligand-target complementarity. <strong>ADMET</strong> analysis predicted low systemic toxicity (<strong>LD₅₀</strong> <strong>= 380</strong>–<strong>530 mg kg⁻¹</strong>) but revealed moderate <strong>CYP3A4/CYP2C9 inhibition</strong>, suggesting the need for metabolic stability evaluation. Compared with reported fusion inhibitors such as EGCG and rutin, this <strong>matrix-targeted strategy</strong> introduces a distinct therapeutic mechanism. Overall, these findings establish a robust computational foundation for developing and experimentally validating potent natural inhibitors against HMPV.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"144 ","pages":"Article 109290"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980434","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":"Y- and Zr-modified boron nitride nanosheets as efficient sensors for formamide: A first-principles approach","authors":"Meryem Derdare,&nbsp;Abdel-Ghani Boudjahem,&nbsp;Nedjoua Cheghib","doi":"10.1016/j.jmgm.2026.109278","DOIUrl":"10.1016/j.jmgm.2026.109278","url":null,"abstract":"<div><div>This study employs DFT calculations to investigate the structural stability and electronic properties of pristine and transition-metal-doped boron nitride (BN) nanosheets, using yttrium (Y) and zirconium (Zr) as dopants, as well as their gas-sensing response toward formamide (FO). The findings show that introducing Y or Zr atoms leads to notable modifications in the electronic structure of the BN nanosheet, substantially improving its chemical reactivity and adsorption performance. In the aqueous phase, the interaction between FO and Y/Zr-doped BN nanosheets becomes moderately weaker, with adsorption energies decreasing to – 4.23 to – 24.97 kcal mol⁻¹; however, the most stable complexes still exhibit comparatively strong binding. Solvation also alters the electronic structure of the nanosheets, leading to noticeable variations in their energy gaps. Despite this reduction in interaction strength, both doped materials retain high sensitivity toward FO in water, with ZrBN reaching 99.9 %/1.43 × 10₃ % and YBN achieving 55.9 %/86.5 %. Moreover, the nanosheets exhibit extremely short recovery times in the liquid phase, with values of 1.27 × 10⁻¹⁵ s for ZrBN and 2.06 s for YBN, enabling rapid FO desorption and efficient restoration of active metal sites. These combined features confirm the strong potential of Y- and Zr-doped BN nanosheets as reusable and high-performance sensors for formamide detection in aqueous environments.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"144 ","pages":"Article 109278"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980542","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":"Evaluating the interactions of L-DOPA and droxidopa toward D3 dopamine receptor through computational study: A comparison with dopamine","authors":"Bhabesh Baro,&nbsp;Biplab Sarkar","doi":"10.1016/j.jmgm.2025.109270","DOIUrl":"10.1016/j.jmgm.2025.109270","url":null,"abstract":"<div><div>The D<span><math><msub><mrow></mrow><mrow><mn>3</mn></mrow></msub></math></span> dopamine receptor (D<span><math><msub><mrow></mrow><mrow><mn>3</mn></mrow></msub></math></span>R), a member of the G protein-coupled receptor family, plays a critical role in neurophysiological processes and has emerged as a potential target for treating neurological disorders such as Parkinson’s disease. In this study, we employed computational approaches to investigate the molecular interactions of D<span><math><msub><mrow></mrow><mrow><mn>3</mn></mrow></msub></math></span>R with dopamine and two key dopamine precursors: L-DOPA and droxidopa. Molecular docking was conducted to evaluate binding affinities and identify key receptor–ligand interactions, followed by molecular dynamics simulations to assess the stability and dynamic behavior of the complexes in a biological environment. MM-PBSA binding free energy calculations were used to further quantify the strength of ligand binding to D<span><math><msub><mrow></mrow><mrow><mn>3</mn></mrow></msub></math></span>R.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"144 ","pages":"Article 109270"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145928866","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":"Dynamic consequences of threonine mutations in the CaLM motif of RET/GFRα1/GDNF ternary complex","authors":"Bithia R.,&nbsp;George Priya Doss C.","doi":"10.1016/j.jmgm.2026.109301","DOIUrl":"10.1016/j.jmgm.2026.109301","url":null,"abstract":"<div><div>The extracellular domain (ECD) of the RET receptor tyrosine kinase depends on its cysteine-rich domain (CRD) for calcium coordination, structural stability, and assembly with GFRα1 and GDNF. Mutations close to the CRD CaLM motif have been associated with disease, but their molecular effects remain understudied. In this study, we analyzed two clinically reported variants, T564N and T564P, using all-atom molecular dynamics simulations of both the isolated CRD and the RET/GFRα1/GDNF ternary complex. Our analysis showed that both the mutations introduced localized structural changes in the CRD monomer. T564N caused increased residue fluctuations at the mutation site and solvent exposure, whereas T564P enhanced flexibility across all calcium-coordinating residues and slightly decreased stabilizing contacts. These effects became more noticeable in the ternary complex. Within the complex, interactions with the neighbouring domains caused the CRD to adopt conformations that compensated for the structural changes observed in the CRD monomer. In this context, each mutation affected calcium-binding energetics differently, resulting in more favourable binding in the mutants than in the wild-type. Although calcium binding was energetically favourable, the overall interaction energy within the complex was still affected. The complex highlighted mutation-specific differences in RET's interactions with GFRα1 and GDNF. The comparison between monomeric and complex simulations indicates that the functional impact of T564 mutations cannot be inferred from the isolated CRD. Together, these results show that the structural and energetic consequences of CRD CaLM mutations depend strongly on the full signaling assembly. This underscores the need to assess RET variants within their native multiprotein environment to understand how disease-associated mutations may alter receptor function.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"144 ","pages":"Article 109301"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079025","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":"Molecular dynamic simulation elucidates temperature- and pH-dependent film-forming mechanisms of soybean β-conglycinin and glycinin","authors":"Meiling Liu ,&nbsp;Yuan Zhao ,&nbsp;Linfan Shi ,&nbsp;Zhongyang Ren ,&nbsp;Wuyin Weng ,&nbsp;Meitian Xiao","doi":"10.1016/j.jmgm.2026.109297","DOIUrl":"10.1016/j.jmgm.2026.109297","url":null,"abstract":"<div><div>The effects of temperature (25–95 °C) and pH (7.0–9.0) on the film-forming mechanisms of soybean <em>β</em>-conglycinin (7S) and glycinin (11S) were investigated using molecular dynamics (MD) simulations and experimental validation. All MD simulations achieved equilibrium within 50 ns. The elevated temperatures and lower pH conditions reduced the center-of-mass distance and the radius-of-gyration (Rg) between 7S and 11S, while increasing hydrogen bond formation and binding free energy. Solvent-accessible surface area decreased with temperature, while root-mean-square fluctuation remained stable at pH 7.0 but increased with temperature at pH 9.0. The 7S-11S films prepared at higher temperatures exhibited enhanced tensile strength and higher proportion of hydrophobic interactions. With increasing temperature of the 7S-11S solution, the elongation at break increased at pH 7.0, but initially increased and then decreased at pH 9.0. Fourier transform infrared spectra revealed that hydrogen bonds and <em>β</em>-sheet structures increased with increasing temperature. In conclusion, heating the film-forming solution at pH 7.0 promoted 7S-11S molecular interactions, thereby improving the mechanical properties.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"144 ","pages":"Article 109297"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003781","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":"Evaluation of CendR peptides mined from protein databases as potential inhibitors of neuropilin-1 using an in-silico molecular modeling approach","authors":"Muslim Raza ,&nbsp;Nurit Haspel ,&nbsp;Anu Sharma ,&nbsp;Sung Hugh Choi ,&nbsp;Xavier De Luna ,&nbsp;Jason J. Evans","doi":"10.1016/j.jmgm.2026.109279","DOIUrl":"10.1016/j.jmgm.2026.109279","url":null,"abstract":"<div><div>Neuropilin 1 (NRP1) mediates lung branching angiogenesis and plays a vital role in cancer progression, especially in solid tumors. Its natural ligands, VEGFA and VEGFB, bind to the b1 binding pocket of NRP1 through hydrophilic c-terminus sites. Viral, bacterial and human proteins have evolved to interact with NRP1, facilitating entry into the cell, and therefore probing databases for hydrophilic CendR sequences could be a useful source of potential inhibitors of NRP1. Molecular docking was used to estimate the binding energies of 4185 naturally occurring CendR peptides to the b1 binding pocket of NRP1. The data predicts that proline, alanine, phenylalanine, leucine, tryptophan and tyrosine in the X positions of XXXXRXXR significantly strengthens the binding of the CendR peptides to the b1 binding pocket of NRP1 and that the presence of glutamic acid, lysine and serine tend to negatively impact binding. Three peptides predicted to have strong affinities and three peptides predicted to have weaker affinities were selected for molecular dynamic (MD) simulations. The data confirms that the interactions between the c-terminal arginine of these CendR peptides with several key residues, including Asp320, Thr316, Tyr297, and Tyr353, of the b1 binding site of NRP1 are particularly stable. During the MD simulations the three peptides predicted to be strong binders showed negative average free energies of interaction, while the three peptides predicted to bind more weakly showed positive free energies of interaction, providing validation of the docking results.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"144 ","pages":"Article 109279"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010722","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":"Integrated experimental and DFT study of dielectric relaxation and optical properties in the chlorobenzene–n-butyl alcohol","authors":"Samir Azizov ,&nbsp;Vusala Nabi Jafarova ,&nbsp;Khayala Ajdar Hasanova","doi":"10.1016/j.jmgm.2026.109305","DOIUrl":"10.1016/j.jmgm.2026.109305","url":null,"abstract":"<div><div>An integrated experimental and first-principles investigation was carried out to elucidate the dielectric relaxation and optical properties of the chlorobenzene–n-butyl alcohol binary system containing 0.25 vol fraction of alcohol. The real (<em>ε</em>′) and imaginary (<em>ε</em>″) parts of the complex dielectric permittivity were measured over microwave wavelengths λ = 2.14–37.9 cm and radio frequencies of 0.047–15 MHz in a wide temperature range from −40 °C to 100 °C. The dielectric spectra in the liquid phase reveal two well-defined Debye-type relaxation regions, which are assigned to the independent reorientation of chlorobenzene and n-butyl alcohol molecules, as well as an asymmetric dispersion near the liquidus–solidus interval that is satisfactorily described by the Davidson–Cole model and attributed to hydrogen-bonded alcohol clusters. These features indicate pronounced microheterogeneity and cluster formation governed by hydrogen bonding. Complementary density functional theory (DFT) calculations were performed to provide atomistic insight into the polarization mechanisms and electronic structure of the chlorobenzene–n-butyl alcohol complex. Optical properties were systematically investigated using both the GGA-PBE approach and the more advanced LDA-RPA framework, allowing assessment of polarization screening and collective excitation effects. The calculations predict a wide band gap of about 4–4.5 eV and reveal strong optical anisotropy in the dielectric function, refractive index, optical conductivity, reflectivity, and absorption spectra, with the dominant response along the hydrogen-bonded molecular axis. The onset of intense π→π∗ and n→σ∗ electronic transitions above 4 eV in both GGA-PBE and LDA-RPA spectra is consistent with the experimentally observed dielectric relaxation and absorption behavior. The close agreement between experimental dielectric measurements and DFT-based optical responses confirms that hydrogen-bond-assisted dipole alignment governs both dielectric relaxation and optical polarization. As a result, the chlorobenzene–n-butyl alcohol system can be classified as a low-loss, wide-band-gap dielectric material, making it a promising candidate for microwave resonators, optoelectronic coatings, and polarization-sensitive sensing applications.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"144 ","pages":"Article 109305"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079022","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 assessment of benzyl C-analogues of dapagliflozin as potential SGLT2 inhibitors for type 2 diabetes","authors":"Mwashi F. Misungwi ,&nbsp;Geradius Deogratias ,&nbsp;Lucas Kwiyukwa ,&nbsp;Sixberth Mlowe ,&nbsp;Andrew S. Paluch ,&nbsp;Lucas Paul","doi":"10.1016/j.jmgm.2026.109321","DOIUrl":"10.1016/j.jmgm.2026.109321","url":null,"abstract":"<div><div>Type 2 diabetes (T2D) is a chronic metabolic disorder managed by drugs like the sodium-glucose cotransporter-2 (SGLT2) inhibitor dapagliflozin. Due to associated adverse effects, the search for safer benzyl C-analogues is warranted. In this <em>in silico</em> study, nine novel analogues (A1–A9) and a reference compound (A10) were evaluated as potential SGLT2 inhibitors. All compounds satisfied drug-likeness criteria and exhibited favourable ADMET profiles, with five classified as toxicity class V.</div><div>Molecular docking and <span><math><mrow><mn>300</mn><mspace></mspace><mtext>ns</mtext></mrow></math></span> molecular dynamics (MD) simulations identified A1 as the most promising candidate. A1 consistently demonstrated the most favourable binding free energy (<span><math><mtext>MM/GBSA</mtext></math></span>: <span><math><mrow><mo>−</mo><mn>152</mn><mo>.</mo><mn>86</mn><mo>±</mo><mn>16</mn><mo>.</mo><mn>27</mn><mspace></mspace><mtext>kJ/mol</mtext></mrow></math></span>) compared to A10 (<span><math><mrow><mo>−</mo><mn>130</mn><mo>.</mo><mn>06</mn><mo>±</mo><mn>11</mn><mo>.</mo><mn>63</mn><mspace></mspace><mtext>kJ/mol</mtext></mrow></math></span>), driven by van der Waals and electrostatic interactions. Furthermore, A1 induced superior dynamic stability, characterized by lower RMSD (<span><math><mrow><mn>0</mn><mo>.</mo><mn>268</mn><mo>±</mo><mn>0</mn><mo>.</mo><mn>023</mn><mspace></mspace><mtext>nm</mtext></mrow></math></span>), reduced SASA (<span><math><mrow><mn>236</mn><mo>.</mo><mn>93</mn><mo>±</mo><mn>3</mn><mo>.</mo><mn>65</mn><mspace></mspace><msup><mrow><mtext>nm</mtext></mrow><mrow><mn>2</mn></mrow></msup></mrow></math></span>), and restricted collective motions (PCA).</div><div>Crucially, the computational ranking strongly correlated with available <em>in vitro</em> data, where A1 exhibited the highest inhibitory potency (<span><math><mrow><msub><mrow><mtext>IC</mtext></mrow><mrow><mn>50</mn></mrow></msub><mo>=</mo><mn>0</mn><mo>.</mo><mn>64</mn><mspace></mspace><mtext>nM</mtext></mrow></math></span>). These combined findings suggest that compound A1 is a promising candidate, which warrants further experimental validation for T2D treatment.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"144 ","pages":"Article 109321"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146180821","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":"Boron and nitrogen-doped coronene as high-performance sensors for gamma-hydroxybutyrate drug sensing: A DFT/TD-DFT study","authors":"Mubarak A. Alamri ,&nbsp;Mohamed Enneiymy ,&nbsp;Yassine Riadi ,&nbsp;Ali Altharawi ,&nbsp;Taibah Aldakhil ,&nbsp;Bharath Kumar Chagaleti ,&nbsp;Ali Oubella ,&nbsp;Reda A. Haggam","doi":"10.1016/j.jmgm.2026.109299","DOIUrl":"10.1016/j.jmgm.2026.109299","url":null,"abstract":"<div><div>Gamma-hydroxybutyrate (GHB) is a psychoactive compound of high clinical and forensic concern due to its involvement in drug-facilitated intoxications and its rapid metabolic clearance, which complicates reliable detection. The reliance of conventional analytical techniques on centralized laboratories and costly instrumentation highlights the urgent need for fast, sensitive, and on-site sensing platforms. While carbon nanomaterial-based sensors have been widely investigated for narcotics detection, the sensing potential of coronene remains largely unknown. In this work, we present the first systematic DFT and TD-DFT investigation of pristine coronene (Cor) and its boron- and nitrogen-doped derivatives (B-Cor and N-Cor) for GHB detection, revealing a clear dopant-dependent sensing functionality. B-Cor emerges as the most effective GHB adsorbent, exhibiting a strong adsorption energy of −13.52 kcal mol⁻¹, a large increase in dipole moment from 0.24 to 2.07 Debye, and enhanced polarizability (290.04–332.70 a.u.). These effects lead to an exceptional bathochromic shift in the UV–Vis spectrum (<em>λ</em>_max from 373 to 594 nm, Δλ = 221 nm) and a decrease in exciton energy from 3.3 to 2.1 eV, establishing B-Cor as a highly promising single-use adsorptive and colorimetric sensor for naked-eye GHB detection. In contrast, N-Cor is identified as an optimal electrochemical sensor, characterized by a dramatically reduced HOMO-LUMO gap (0.57 eV), high chemical softness (1.75 eV^-1), elevated electrical conductivity (2.75 × 10⁹ A.m⁻²), and an ultra-fast recovery time of 5.63 × 10⁻⁶ s, enabling rapid and reusable sensing. Moderate increases in dipole moment (0.21–0.72 Debye) and polarizability (283.06–325.85 a.u.) further support its strong electronic responsiveness upon GHB binding. By distinctly identifying B-Cor as a superior adsorbent and colorimetric sensor and N-Cor as an efficient electrochemical sensor, this study introduces coronene as a versatile and tunable sensing scaffold and provides a robust theoretical foundation for the rational design of next-generation GHB sensing platforms for forensic and clinical applications.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"144 ","pages":"Article 109299"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035985","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}