Journal of molecular graphics & modelling最新文献

{"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":"Computational modeling of ubiquitin specific protease 7 (USP7) complexes with N-benzylpiperidinol derivatives incorporating binding site flexibility","authors":"Jorge Luis Valdés-Albuernes,&nbsp;Erbio Díaz-Pico,&nbsp;José Luis Velázquez-Libera,&nbsp;Julio Caballero","doi":"10.1016/j.jmgm.2025.109272","DOIUrl":"10.1016/j.jmgm.2025.109272","url":null,"abstract":"<div><div>Ubiquitin-specific protease 7 (USP7) is a key regulator of protein homeostasis, playing critical roles in various cellular processes, including DNA damage response, immune signaling, and oncogenesis. Targeting USP7 with small-molecule inhibitors has emerged as a promising therapeutic strategy, particularly in the context of cancer and autoimmune diseases. Among the diverse scaffolds explored for USP7 inhibition, <em>N</em>-benzylpiperidinol (NBP) derivatives have shown notable potential due to their structural versatility and bioactivity. Computationally, it is possible to access models of complexes between these inhibitors and USP7 by utilizing the crystallographic structures of USP7 available in the Protein Data Bank. In a classical approach, models of NBPs can be obtained within a rigid USP7 structure. In this work, we report models of complexes between 58 NBPs and variable conformations of USP7 using a flexible docking protocol employing the novel CorrEA method. As part of this protocol, we obtained diverse USP7 structures through molecular dynamics (MD) and selected complex models with inhibitors based on their biological activities. Model quality was validated using LigRMSD and interaction fingerprints (IFP). The flexible treatment of USP7 enabled the capture of binding-site conformational changes. These changes are critical for explaining the activity differences among the studied compounds.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"144 ","pages":"Article 109272"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145928864","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}

{"title":"A molecular dynamics study of PIM2 lipid bilayer membranes","authors":"Yago Mendes Paes ,&nbsp;João L.R. Scaini ,&nbsp;Vania R. de Lima ,&nbsp;Adriano Velasque Werhli ,&nbsp;Pedro Almeida da Silva ,&nbsp;José Rafael Bordin ,&nbsp;Karina dos Santos Machado","doi":"10.1016/j.jmgm.2026.109284","DOIUrl":"10.1016/j.jmgm.2026.109284","url":null,"abstract":"<div><div>Developing simplified yet representative models of the complex <em>Mycobacterium tuberculosis</em> inner membrane is crucial for advancing Molecular Dynamics of this pathogen. Phosphatidyl-myo-inositol dimannosides (PIM<span><math><msub><mrow></mrow><mrow><mn>2</mn></mrow></msub></math></span>), one of the most abundant lipids in this membrane, provides an ideal basis for such a model. In this study, we proposed a minimal, single-component atomistic PIM<span><math><msub><mrow></mrow><mrow><mn>2</mn></mrow></msub></math></span> bilayer for use in <em>M. tuberculosis</em> research. We validate the model by assessing its ability to reproduce distinct temperature-dependent ordering regimes, with a more ordered, gel-like behavior at 310 K and increased fluidity at 363.15 K, its capacity for spontaneous self-assembly, and its interaction with the native transmembrane efflux pump, Tap (Rv1258c). Our simulations confirm that the model exhibits the correct phase behavior at experimental temperatures and readily self-assembles into an extended lamellar bilayer-like structure. Importantly, the PIM<span><math><msub><mrow></mrow><mrow><mn>2</mn></mrow></msub></math></span> membrane provides a significantly more stable environment for the embedded Tap protein compared to a standard dipalmitoylphosphatidylcholine (DPPC) bilayer. These findings confirm the PIM<span><math><msub><mrow></mrow><mrow><mn>2</mn></mrow></msub></math></span> bilayer as a robust and promising model. It is particularly well suited for investigating the protein–lipid interactions central to multidrug resistance in <em>M. tuberculosis</em> and for exploring phenomena such as the bacterial immunological thermostat.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"144 ","pages":"Article 109284"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146029906","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":"Effects of taurine on the ion solvation scenario and its counteraction against the urea-induced denaturation of protein","authors":"Chinmay Parida,&nbsp;Pragin Chettiyankandy,&nbsp;Deepak Kumar Mahanta,&nbsp;Snehasis Chowdhuri","doi":"10.1016/j.jmgm.2026.109315","DOIUrl":"10.1016/j.jmgm.2026.109315","url":null,"abstract":"<div><div>Molecular dynamics (MD) simulations have carried out to investigate the solvation scenario of ions (Na⁺, K⁺, Cl⁻, I⁻, NH₄⁺, CH₃COO⁻) in the binary water-taurine and ternary water-taurine-urea mixtures at 308 K. The hydrogen bond (H-bond) properties and dynamics of water‒water, taurine‒water, and ammonium/acetate ion‒water are also explored. Our study revealed that monovalent cations have a higher tendency towards oxygen of taurine than water. NH₄⁺ preferably interacts with the oxygen of the sulfonate group, whereas acetate ions are attributed towards the amino-hydrogens of taurine compared to the oxygen and hydrogens of water. It is found that taurine forms stronger H-bonds with water molecules through its amino group indicating the higher donating tendency of taurine. The translational and orientational relaxation dynamics of water molecules are slowed down in both the binary and ternary mixtures. The average lifetime of the water's H-bonds is higher in the ternary mixtures than the binary mixtures. Addition of urea enhances the overall lifetime of the ammonium ion-water (H_AMM…O_WAT) and acetate ion-water (O_ACE…H_WAT) H-bonds. We have also observed that taurine counteracts the denaturation effect of urea on human islet amyloid polypeptide (hIAPP), as evidenced by the secondary structure. The α-helix content of hIAPP is restored with the addition of 0.45 M taurine in 5.60 M urea concentrations.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"144 ","pages":"Article 109315"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142674","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 drug delivery potential of functionalized calix [4] arene for carboplatin-drug: A computational study analyzing static electric field and solvent effects through DFT, TD-DFT, and NLO techniques","authors":"M. Rezaei-Sameti,&nbsp;M. Heydari","doi":"10.1016/j.jmgm.2026.109275","DOIUrl":"10.1016/j.jmgm.2026.109275","url":null,"abstract":"<div><div>Targeted and precise drug delivery using nanomaterials remains a major goal in cancer therapy. In this study, the interaction of carboplatin, a key anticancer drug, with pristine and functionalized calix[4]arene (CHO, COOH, NH₂, NO₂) was investigated under varying solvent environments (water, ethanol, DMSO) and static electric fields (SEF) using density functional theory (DFT) at the GD3-Cam-B3LYP/Lanl2DZ level. The negative adsorption energy (E_ads) and enthalpy (ΔH) values confirm exothermic and thermodynamically favorable interactions across all complexes. Among them, CC-NO₂-II exhibits the highest E_ads (−32.54 kcal/mol in the gas phase), while CC-COOH derivatives demonstrate exceptional stability across solvents due to strong hydrogen bonding and dipolar interactions. Under SEF (z+0.05 a.u.), CC-NH₂ exhibits the most significant enhancement in E_ads (−276.01 kcal/mol), highlighting its potential for field-assisted drug delivery. The CC-COOH complex shows the greatest E_gap reduction (83.6 %), attributed to its high dipole moment and polarizability. Non-covalent interactions, including hydrogen bonding, van der Waals forces, and electrostatic interactions, were confirmed through atoms-in-molecules (AIM) and reduced density gradient (RDG) analyses. These findings underscore the potential of functionalized calix [4] arene as an efficient and tunable drug carrier, with external fields and solvents serving as effective modulation factors. This work provides valuable insights for the molecular design of advanced, field-responsive drug delivery systems for targeted chemotherapy applications.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"144 ","pages":"Article 109275"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079128","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}