Journal of molecular graphics & modelling最新文献

{"title":"Structure-based design of a multi-epitope vaccine candidate against marburg virus using immunoinformatics and dynamics simulations.","authors":"Mohamed J Saadh, Faris Anad Muhammad, Rafid Jihad Albadr, Suhas Ballal, Abhayveer Singh, Anita Devi, Kamal Kant Joshi, Saida Saidkhodjaeva, Waam Mohammed Taher, Mariem Alwan, Mahmood Jasem Jawad, Ali M Ali Al-Nuaimi","doi":"10.1016/j.jmgm.2025.109130","DOIUrl":"10.1016/j.jmgm.2025.109130","url":null,"abstract":"<p><p>The Marburg virus, a close relative of the Ebola virus, is a menacing Filovirus known for its devastating outbreaks in Germany and recent outbreaks in Guinea and Tanzania. This deadly pathogen triggers severe hemorrhagic fever, posing a grave threat to public health and demanding urgent attention from the global medical community. The amino acid sequence and PDB of the Envelope glycoprotein (GP) were extracted from RCSB for use in predicting epitopes (IEDB server). The construction of the multi-epitope vaccine included an adjuvant and linkers (AAY, EAAAK, GPGPG), which were assessed with the ProtParam tool to characterize their physico-chemical properties. Additionally, modeling was carried out with the Robetta server, and the modeled vaccine was docked with Toll-like receptor 4 (TLR4). Finally, immune and molecular dynamic simulations were implemented using the C-ImmSim and GROMACS packages. The final multi-epitope vaccine consists of 211 amino acids, created with 5 CTL and 4 HTL epitopes that were validated and passed assessments for antigenicity, allergenicity, and toxicity. The modeled multi-epitope vaccine was evaluated and demonstrated high model quality. The best molecular docking candidate was selected and evaluated using PDBsum. Subsequently, by assessing RMSD, RMSF, and Gyration, the molecular dynamic simulation revealed considerable binding with TLR4, and the complex remained stable throughout the simulation. Ultimately, the multi-epitope vaccine can stimulate both humoral and cell-mediated immune responses, validated computationally. The overall implication of this investigation shows the potency of the multi-epitope construct as an efficient protective vaccine against the Marburg virus.</p>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"141 ","pages":"109130"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812116","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":"Efficient structure elucidation and investigation on the antibacterial activity of Carbamide-Butanedioic Acid: DFT perspectives.","authors":"Radhika P V, J T Anandhi, S K Amjath Kudos, R S Bemina, Binisha B, S Madhan Kumar, T Joselin Beaula","doi":"10.1016/j.jmgm.2025.109137","DOIUrl":"10.1016/j.jmgm.2025.109137","url":null,"abstract":"<p><p>In the quest to combat rising antimicrobial resistance, this study explores the synthesis, characterization, and pharmacological potential of carbamide compounds combined with Butanedioic acid. Leveraging both experimental and computational methodologies, we synthesized Carbamide-Butanedioic Acid (CBA) crystals through a controlled evaporation process. Characterization was conducted using techniques such as FT-IR, UV-visible spectroscopy, powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). These methods elucidated the crystal structure, molecular interactions, and physicochemical properties of the synthesized compounds. Computational studies, employing Density Functional Theory (DFT) and other quantum chemical calculations, provided insights into the molecular geometry, vibrational spectra, and electronic properties, including the identification of reactive sites and intermolecular interactions. The antibacterial efficacy of the synthesized compounds was assessed using the agar well diffusion method, revealing promising inhibitory effects against bacterial pathogens. This study highlights CBA compounds as promising next-generation antibacterial agents, providing a new approach to tackle antimicrobial resistance.</p>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"141 ","pages":"109137"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812115","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":"Comparative efficiency of structure activity relationship and proteochemometric modelling.","authors":"Georgy S Malakhov, Dmitry A Karasev, Boris N Sobolev","doi":"10.1016/j.jmgm.2025.109134","DOIUrl":"10.1016/j.jmgm.2025.109134","url":null,"abstract":"<p><p>Virtual screening of biologically active compounds is widely applied for the search of drug leads. The well-known methods of structure-activity relationship (SAR) are based on the chemical structure comparison. In the last years, an approach known as proteochemometrics (PCM) has also gained popularity. PCM extends the capabilities of SAR by incorporating the protein target descriptors into the model. Unlike SAR, PCM can be used to predict new targets with unknown spectra of ligands. As both approaches can be used to predict ligands for the known proteins, several researchers apply PCM to solve this task, without providing compelling reasons to support the superiority of the PCM approach over SAR. To correctly compare the performance of SAR and PCM in the given situation, we have developed a special validation scheme. As a result, we did not find any advantages of PCM over SAR in the prediction of ligands for the protein with an established ligand spectrum. At the same time, the validation procedure commonly used for PCM models considerably inflates the evaluation scores compared to our technique. Widespread use of such validation scheme leads to conclusions that PCM has great advantage over SAR in contrast to our findings. Thus, our study emphasizes that a transparent and correct validation scheme is essential for comparison of different methods.</p>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"141 ","pages":"109134"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812114","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":"Phytochemicals from Bacopa monnieri as small molecule modulators of MARK4: A multi-modal strategy for preventing Alzheimer's disease-causing tau aggregation.","authors":"S Rehan Ahmad, Md Zeyaullah, Yousef Zahrani, Mohammad Suhail Khan, Khursheed Muzammil, Adam Dawria","doi":"10.1016/j.jmgm.2025.109135","DOIUrl":"10.1016/j.jmgm.2025.109135","url":null,"abstract":"<p><p>Neurodegenerative tauopathies, such as Alzheimer's disease, are closely associated with the dysregulation of tau phosphorylation, a process regulated in part by the serine/threonine kinase MARK4. In this study, we explored phytochemicals derived from Bacopa monnieri as potential natural inhibitors of MARK4. Using pressurized liquid extraction with an ethanol-water mixture, we efficiently extracted bioactive compounds from Bacopa leaves. LC-MS analysis identified 25 distinct phytoconstituents spanning flavonoids, triterpenoids, cucurbitacins, sterols, and alkaloids. In silico analysis revealed that several compounds, including oroxindin, cucurbitacin B, and bacosine, bind strongly to the catalytic pocket of MARK4. Molecular dynamics simulations confirmed their stability within the MARK4 active site, with oroxindin demonstrating the most favorable thermodynamic and conformational profile. Principal component and free energy landscape analyses further supported their capacity to stabilize MARK4 in low-energy conformations. Microscale thermophoresis further validated high-affinity binding of MARK4 with oroxindin, while other four compounds also show strong interaction with MARK4. MTT assays in SH-SY5Y cells confirmed the non-cytotoxic nature of all five lead compounds across a concentration range of 10 nM to 10 μM. Cellular assays revealed a significant reduction in Tau-GFP aggregates upon treatment with the compounds, particularly oroxindin. These results highlight oroxindin and other Bacopa monnieri phytochemicals as promising natural inhibitors of MARK4, with potential to attenuate tau pathology in neurodegenerative diseases.</p>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"140 ","pages":"109135"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799376","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":"Engineering graphyne-supported single-atom catalysts for efficient nitrogen reduction to ammonia: First-principles investigation.","authors":"Nahed H Teleb, Yasmeen G Abou El-Reash, Nuha Y Elamin, Mahmoud A S Sakr, Mohamed A Saad, Hazem Abdelsalam","doi":"10.1016/j.jmgm.2025.109136","DOIUrl":"10.1016/j.jmgm.2025.109136","url":null,"abstract":"<p><p>The electrochemical nitrogen reduction reaction (N₂RR) offers a sustainable route to ammonia production under ambient conditions but remains limited by inert N ≡ N bond activation and competitive hydrogen evolution reaction (HER). Herein, we employ first-principles density functional theory (DFT) to systematically investigate the N₂RR activity of graphyne (GY) doped with single-atom transition metals (Fe, Mo, Ru, W). Structural analysis reveals strong binding and minimal distortion of the TM dopants on the porous, π-conjugated GY scaffold, with Fe-GY and W-GY exhibiting the highest stability. TM doping induces substantial bandgap narrowing and introduces localized d-orbital states near the Fermi level, enhancing charge transfer and catalytic potential. Adsorption studies show that TM sites effectively activate N₂ via π-backdonation, with W-GY inducing the greatest N ≡ N bond elongation. Free energy profiles demonstrate that TM-GY catalysts significantly lower the limiting potential for N₂RR compared to pristine GY, with Fe-Gy and W-GY achieving the most favorable limiting potential via the alternating mechanism. HER analysis reveals Ru-GY possesses near-optimal hydrogen adsorption energy (ΔG_H = -0.25 eV), suggesting high activity but possible competition with N₂RR. In contrast, Mo-GY and W-GY exhibit stronger H binding, potentially suppressing HER and improving N₂RR selectivity. This work identifies TM-doped GY as a versatile platform for single-atom catalysis and offers design principles for optimizing selectivity and efficiency in electrochemical nitrogen fixation.</p>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"140 ","pages":"109136"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804180","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":"Decomposition of 5-(Dinitromethylene)-4,5-dihydro-1H-1,2,4-triazole at elevated temperatures coupled with high pressures: A molecular dynamics study.","authors":"Dandan Li, Wenpeng Wang, Xinwei Cao","doi":"10.1016/j.jmgm.2025.109190","DOIUrl":"https://doi.org/10.1016/j.jmgm.2025.109190","url":null,"abstract":"<p><p>The thermal decomposition mechanisms of 5-(dinitromethylene)-4,5-dihydro-1H-1,2,4-triazole (DNMDHT), a FOX-7 derivative, were systematically investigated under extreme conditions via ReaxFF-lg reactive molecular dynamics simulations. Two distinct regimes were examined: (1) high-temperature conditions (2500-3500 K) and (2) combined high-temperature-high-pressure conditions (3000 K, 0-50 GPa). There are two possible decomposition pathways for DNMDHT-FOX, one of which is that the DNMDHT-FOX molecule will first undergo condensation under high-temperature, and polymerized to form a polymer under high-pressure, then the decomposition pathway initiates with sequential C-N bond cleavages, first eliminating nitro groups followed by ring-opening, succeeded by C=C and C=N bond ruptures. Primary decomposition products include H₂O, CO₂, N₂, H₂, and NH₃ as stable products, with NO₂, NO, and CO identified as key intermediates. Notably, pressure-dependent studies revealed NH₃ yields increase monotonically with pressure (0-50 GPa), while all other product yields demonstrate inverse pressure dependence. These findings establish that temperature accelerates decomposition kinetics whereas pressure exerts an inhibitory effect, except for NH₃ formation. This work provides fundamental insights into the decomposition chemistry of energetic FOX-7 derivatives under extreme conditions, offering valuable guidance for the design and safety evaluation of novel high-energy materials.</p>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"142 ","pages":"109190"},"PeriodicalIF":3.0,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286405","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":"Predictive modeling of physicochemical properties of antihypertensive drugs using degree-based topological indices and machine learning algorithm","authors":"Saood Azam,&nbsp;Sadia Noureen,&nbsp;Tasra Yaqoob","doi":"10.1016/j.jmgm.2025.109189","DOIUrl":"10.1016/j.jmgm.2025.109189","url":null,"abstract":"<div><div>Quantitative prediction of physicochemical properties through molecular graph theory has become an important focus in cheminformatics. This study introduces a set of degree-based topological indices—ABC, ABS, MMR, SDD, SI, SO, SO<span><math><msub><mrow></mrow><mrow><mn>3</mn></mrow></msub></math></span>, and SO<span><math><msub><mrow></mrow><mrow><mn>4</mn></mrow></msub></math></span>—to model 23 antihypertensive drugs. A QSPR framework is developed using both classical linear regression and ensemble-based machine learning algorithms (Random Forest and XGBoost). Model performance is evaluated using standard error metrics (MAE, MSE, RMSE, <span><math><msup><mrow><mi>R</mi></mrow><mrow><mn>2</mn></mrow></msup></math></span>), and feature importance is analyzed through Gini, permutation, and Shapley Additive exPlanations (SHAP). The proposed indices show strong correlations with boiling point, melting point, critical volume, LogP, molar refractivity, and CLogP. Among the tested models, XGBoost performs best, achieving <span><math><mrow><msup><mrow><mi>R</mi></mrow><mrow><mn>2</mn></mrow></msup><mo>&gt;</mo><mn>0</mn><mo>.</mo><mn>99</mn></mrow></math></span> across all properties. Beyond predictive accuracy, the findings show that degree-based indices capture structural features of drug molecules while offering interpretable insights into lipophilicity, stability, and thermodynamic behavior. These results demonstrate the potential of graph-theoretical descriptors as cost-effective alternatives to experimental assays, thereby accelerating rational drug design and screening workflows. Overall, this study establishes a generalizable modeling framework that bridges mathematical chemistry and pharmaceutical applications, providing valuable directions for high-throughput drug discovery.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"142 ","pages":"Article 109189"},"PeriodicalIF":3.0,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145267855","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":"Interpretable support vector classifier for reliable prediction of antibacterial activity of modified peptides against Escherichia coli","authors":"Remmer L. Salas ,&nbsp;Portia Mahal G. Sabido ,&nbsp;Ricky B. Nellas","doi":"10.1016/j.jmgm.2025.109188","DOIUrl":"10.1016/j.jmgm.2025.109188","url":null,"abstract":"<div><div>Antimicrobial peptides (AMPs) are promising alternatives to traditional antibiotics, whose effectiveness is declining due to rising antimicrobial resistance (AMR). To accelerate AMP discovery, we developed ISCAPE (<strong>I</strong>nterpretable <strong>S</strong>upport Vector <strong>C</strong>lassifier of <strong>A</strong>ntibacterial Activity of <strong>P</strong>eptides against <strong><em>E</em></strong><em>scherichia coli</em>), a machine learning (ML) model that addresses the limitations of current AMP predictors. ISCAPE requires only a Simplified Molecular-Input Line-Entry System (SMILES) string as input and can predict the activity of both natural and chemically modified peptides against <em>E. coli</em> ATCC 25922. Activity is defined by a minimum inhibitory concentration (MIC) threshold of ≤16 μg/mL. To ensure reliability, only MIC values obtained under comparable experimental conditions were included in our curated dataset. ISCAPE outperformed the state-of-the-art AntiMPmod, achieving an area under the receiver operating characteristic curve (AUROC) of 91.83% and a Matthew's correlation coefficient (MCC) of 71.86%. Features driving this performance include the fraction of carbon-carbon pairs and feature- and count-based extended connectivity fingerprints (ECFPs). Model interpretability is enhanced through SHapley Additive exPlanations (SHAP), which identifies the molecular features most critical for AMP activity. To our knowledge, ISCAPE is the first interpretable ML predictor capable of predicting antibacterial activity for both natural and modified peptides against a specific <em>E. coli</em> strain. It is a user-friendly tool that allows experimentalists to pinpoint key molecular features, reducing the need for extensive structure-activity relationship (SAR) studies and guiding the design of novel AMPs.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"142 ","pages":"Article 109188"},"PeriodicalIF":3.0,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145267854","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":"Structure-based identification of small molecule inhibitors targeting trigger factor and peptidyl prolyl cis/trans isomerase B (PpiB) of Bacillus anthracis Sterne: Towards new therapeutic interventions against anthrax","authors":"Roopshali Rakshit ,&nbsp;Aayush Bahl ,&nbsp;Gargi Gautam ,&nbsp;Saurabh Pandey ,&nbsp;Deeksha Tripathi","doi":"10.1016/j.jmgm.2025.109185","DOIUrl":"10.1016/j.jmgm.2025.109185","url":null,"abstract":"<div><div>Anthrax, caused by <em>Bacillus anthracis</em>, remains a critical zoonotic threat, with treatment efficacy increasingly compromised by advanced infection progression and rising antibiotic resistance. This study leverages integrative computational strategies to identify and characterize novel therapeutic targets among previously uncharacterized molecular chaperones-Trigger Factor (BASTig) and peptidyl-prolyl <em>cis-trans</em> isomerase B (BASPpiB)-from <em>B. anthracis</em> Sterne. Structural elucidation using homology modelling and AlphaFold revealed distinctive architectures for BASTig (425 residues) and BASPpiB (145 residues). High-throughput virtual screening of diverse chemical libraries pinpointed compounds 51002 and 50423 as promising inhibitors, with strong binding affinities of −52.58 and −66.4 kcal/mol, respectively. ADME profiling confirmed favourable drug-like properties, and molecular dynamics simulations demonstrated stable protein–ligand interactions. Quantum mechanical calculations further supported the electronic complementarity and thermodynamic stability of these complexes. Electrostatic surface potential (ESP) analysis revealed that compound 51002 features predominantly positive charge distributions, favouring interactions with acidic residues in BASTig, while compound 50423 displays heterogeneous electrostatic regions, enabling adaptive binding to BASPpiB's dynamic pocket. Toxicity predictions indicated acceptable safety profiles for both leads. Immunogenicity assessment showed differential antigenic potential (BASPpiB: 100 %, BASTig: 66 %). Epitope mapping with ABCpred identified multiple high-scoring, spatially distributed B-cell epitopes in both proteins, with substantial concordance between predictive algorithms. These results highlight the therapeutic promise of targeting molecular chaperones in <em>B. anthracis</em> and provide a foundation for both small-molecule drug discovery and rational immunogen design, addressing urgent needs in anthrax intervention and antimicrobial resistance.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"142 ","pages":"Article 109185"},"PeriodicalIF":3.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232652","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 insights on the binding site and function of cannabinoids and cannabinoid acids on human 5-HT1A receptor","authors":"Beow Keat Yap ,&nbsp;Scott Palmer ,&nbsp;Thomas Piccariello","doi":"10.1016/j.jmgm.2025.109186","DOIUrl":"10.1016/j.jmgm.2025.109186","url":null,"abstract":"<div><div>Previous studies reported that the acid congener of the cannabinoids, cannabidiolic acid, was approximately 1000 times more effective than the neutral congener, cannabidiol, in alleviating emesis. The biological actions of cannabinoids were proposed to be mediated by the enhancement of somatodendritic 5-HT_1A receptors. However, to date, the potential mechanism that may be involved in the enhancement of the 5-HT_1A activity by the acid congener is still lacking. To address this gap, molecular docking and molecular dynamics simulations were performed on different pairs of neutral and acidic cannabinoids in a human 5-HT_1A receptor model. Analyses showed that simulated cannabinoid acids (cannabidiolic acid and tetrahydrocannabivarinic acid) and tetrahydrocannabivarin were preferentially bound at the allosteric site of 5-HT_1A and were able to maintain the receptor in its active state when a full agonist, R(+)-8-OH-DPAT, was bound at the orthosteric site. Importantly, these results also suggest that the strong activity of cannabidiolic acid is not due to its strong affinity for the 5-HT_1A receptor but its positive allosteric modulation of the agonist activity on 5-HT_1A, presumably by blocking the exit of the orthosteric ligand, hence promoting continuous activation of the receptor. This study also demonstrates that cannabidiol and both neutral and acidic cannabigerol prefer binding at the orthosteric site and are potential partial agonists of 5-HT_1A. In conclusion, these findings propose that every cannabinoid, regardless of whether neutral or acidic, is unique on its own in terms of its binding and function.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"142 ","pages":"Article 109186"},"PeriodicalIF":3.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244577","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}