In silico pharmacology最新文献

{"title":"Deciphering the immunomodulatory mechanisms of piperine during HIV-Mtb co-infection: network pharmacology, docking and molecular dynamics.","authors":"Ankur Gupta, Anusha Chettri, Pratiksha Khanal, Salika Aru Gupta, Santi Chettri, Phunchok Norbu Sherpa, Jun Moni Kalita, Dhrubajyoti Gogoi","doi":"10.1007/s40203-026-00754-w","DOIUrl":"10.1007/s40203-026-00754-w","url":null,"abstract":"<p><p>Human immunodeficiency virus (HIV) and <i>Mycobacterium tuberculosis</i> (Mtb) co-infection synergistically weakens the host immune system. Previous studies have investigated the involvement of multiple signalling pathways and genes such as TNF, IL6, PI3K-AKT1, and JAK/STAT3 in regulating host immune functions during HIV and Mtb infection. These pathways have also been explored for apoptosis, autophagy, and anti-neoplastic activity of several bioactive compounds, including piperine, the major alkaloid of Piper nigrum. However, the therapeutic potential of piperine in modulating host immune responses during HIV/Mtb co-infection has not been studied. Therefore, the present investigation aims to elucidate the potential immunomodulatory role of piperine during HIV/Mtb co-infection using network pharmacology, docking and molecular dynamics (MD) simulations. The gene targets related to HIV, Mtb, and piperine were retrieved from public databases. Common gene targets were identified using Venny 2.0.2/Appyters. Protein-protein interaction (PPI) networks were constructed via STRING and analysed with Cytoscape to determine hub genes. Gene Ontology (GO) enrichment and KEGG pathway analyses were carried out using SRplot. Our study identified 78 potential therapeutic targets and 20 hub genes associated with piperine. Among these, TNF, IL6, AKT1, STAT3 and CASP3 emerged as central targets across the top signalling pathways during HIV/Mtb co-infection. Molecular docking demonstrated strong binding affinities of piperine with host, HIV, and Mtb targets, showing binding energies between - 6.0 and - 9.2 kcal/mol. Furthermore, 100 ns molecular dynamics simulations confirmed the structural stability of the selected protein-ligand complexes, exhibiting low structural deviations, limited residue fluctuations, preserved protein compactness, and persistent hydrogen-bond interactions throughout the simulation period. These findings suggest that piperine could serve as a promising immunomodulatory compound in the treatment of HIV/Mtb co-infection.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at https://doi.org/10.1007/s40203-026-00754-w.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"250"},"PeriodicalIF":0.0,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149066844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of potential RdRp catalytic domain inhibitors against Crimean-Congo hemorrhagic fever virus from <i>Andrographis paniculata</i> via LC-MS/MS profiling and computational approaches.","authors":"Abdul Rehman Riaz, Muhammad Islam, Hamid Saeed, Kalim Ullah, Aneeqa Saleem","doi":"10.1007/s40203-026-00755-9","DOIUrl":"10.1007/s40203-026-00755-9","url":null,"abstract":"<p><p>Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic zoonotic virus associated with significant mortality and currently lacks FDA-approved therapeutic options. Owing to its endemic nature and epidemic potential, it has been included in WHO priority pathogen list under its R&D Blueprint, highlighting the urgent need for development of novel antiviral agents. The present study explores antiviral potential of phytoconstituents from <i>Andrographis paniculata</i> targeting viral catalytic domain of RNA-dependent RNA polymerase (RdRp). Cold Ethanolic leaf extract was prepared using ultrasonic-assisted extraction and subjected to LC-MS/MS QQQ profiling, leading to identification of 44 phytochemicals, mostly andrographolide diterpenes lactones and flavonoids. Among these, 11 major compounds were selected based on abundance and spectral reliability for computational evaluation. Molecular docking revealed strong binding affinities of bisandrographolide (- 8.212 kcal/mol), andrographiside (- 7.659 kcal/mol), 3-O-β-D-glucopyranosyl-andrographolide (- 7.653 kcal/mol), andrographidin A (- 7.540 kcal/mol) and neoandrographolide (- 7.353 kcal/mol) towards the catalytic domain of RdRp which is comparable to standard Ribavirin (- 8.314 kcal/mol). MD simulations of 100 ns were performed which demonstrated stable <i>Andrographis paniculata</i> ligand-RdRp complexes through consistent RMSD, RMSF, radius of gyration, hydrogen bonding, minimum distance (~ 0.25-0.30 nm) and SASA profiles, except for neoandrographolide, showed comparatively lower conformational stability. In silico ADMET analysis indicated generally acceptable pharmacokinetic and safety profiles, although some compounds exhibited low GIT absorption. Collectively, results suggest that <i>Andrographis paniculata</i> phytoconstituents, particularly andrographolide diterpenes lactones possess promising inhibitory potential against catalytic domain of CCHFV RdRp and may serve as lead candidates for antiviral drug development. Further mechanistic studies are needed to elucidate exact mode of RdRp catalytic domain inhibition while in vitro and in vivo validation is crucial to confirm their therapeutic potential and translational relevance.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"249"},"PeriodicalIF":0.0,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149066867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abietic acid attenuates hyperglycemia and oxidative stress via TLR4-mediated inflammation and PPAR-γ-Nrf2 activation: evidence from network pharmacology and in vivo validation.","authors":"Akash Mishra, Hital Shah","doi":"10.1007/s40203-026-00743-z","DOIUrl":"10.1007/s40203-026-00743-z","url":null,"abstract":"<p><p>To reconnoitre the mechanism of Abietic acid (AA) in diabetes by <i>in-silico</i> and <i>in-vivo</i> experiments. Using GeneCards, diabetes gene targets were obtained. The protein-protein interaction and network topology analysis were performed using the String platform and Cytoscape 3.7.2. The enrichment analysis was done by Shiny GO. The docking was by Autodeck. Diabetes was induced by injecting STZ (55 mg/kg, i.p once) in Sprague-Dawley rats. The parameters included glucose, lipids, blood pressure, ECG, OGTT, kidney and cardiac markers, liver enzymes, AMPK, Nrf2, PPAR-γ, TLR-4, oxidative markers, LVF tests, and histopathology. AA interacts with 15 important targets (PIK3CD, MAPK1, NF-κB, mTOR, STAT3, GRIN1, ITGB3, ACACA, HSP90AB1, SERPINE1, ADRB1, ULK1, TLR4, CTSD, CDK5). The signalling pathways, like insulin, MAPK1, TLR, AMPK, JAK-STAT, are associated with these proteins. In docking, the highest affinity of AA was observed for ITGB3 (- 8.1), TLR4 (- 7.8), and ACACA (- 7.3). In rats, AA(40 and 80 mg/kg) decrease hyperglycaemia and hyperinsulinemia, improves glucose tolerance, normalize blood pressure, combat dyslipidaemia (decrease triglyceride, total cholesterol, LDL, increase HDL), preserves myocytes and ventricular function (decrease troponin-I, LDH, CK-MB, LVEDP, normal ECG), hepatoprotective (decrease AST, ALT), reno-protective (decrease creatinine, urea, uric acid) and combat oxidative stress (decrease MDA, increase SOD, catalase). Nrf2, AMPK, and PPAR γ levels were increased while TLR-4 levels were decreased after AA treatment. The study is supported by the preserved histopathological architecture of pancreatic, renal, hepatic, and cardiac cells. The present study preliminarily clarifies that AA exhibits therapeutic potential in preclinical models through multitargets and multi-pathways (Nrf/TLR4/PPAR γ), which points out a new direction for further research and clinical application.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"245"},"PeriodicalIF":0.0,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149066902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico evaluation of physicochemical properties, drug-likeness, molecular docking, MD simulations and MM-PBSA energy calculations of bioactive compounds from antarctic sponge <i>Suberites</i> sp. against SARS-CoV-2 main proteases.","authors":"Amit Ranjan Pandey, Amit Anand Panday, Alok Dwivedi, Volkan Eyüpoğlu, Ravi Rawat, Rishi Ranjan Pandey","doi":"10.1007/s40203-026-00736-y","DOIUrl":"10.1007/s40203-026-00736-y","url":null,"abstract":"<p><p>Building on prior research by Joe Bracegirdle and colleagues, who isolated sesterterpene compounds (1-11) from the Antarctic sponge <i>Suberites</i> sp., including Suberitenones A, B, and F, which exhibited antiviral activity against RSV, this study explored the potential of these compounds as inhibitors of the SARS-CoV-2 main proteases (PDB IDs: 6LU7 and 6W63) utilising in silico drug design approaches. All the ligands were subjected to molecular docking with the SARS-CoV-2 main protease. The results indicated significant binding affinities, ranging from - 6.1 to -7.6 kcal/mol for 6LU7 and - 6.8 to -8.2 kcal/mol for 6W63. Further assessment of their ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties and drug-likeness revealed favourable pharmacokinetic characteristics for these compounds. Among them, Suberitenone E (2) and Suberitenone I (6) stood out as the most promising. Compound 2 exhibited a strong binding affinity of -8.2 kcal/mol with 6W63. In comparison, compound 6 showed an affinity of -7.6 kcal/mol with 6LU7, both demonstrating robust interactions with the SARS-CoV-2 main protease receptor and acceptable ADMET profiles. The stability and binding strength of these ligand-protease complexes were further confirmed through molecular dynamics simulations and MMPBSA energy calculations. Molecular dynamics simulations assessed the binding affinity of two compounds to the SARS-CoV-2 main protease receptors. Among the 11 ligands tested, compounds 2 and 6 exhibited superior binding affinity. This suggests their potential for modulating enzyme activity and potential relevance in COVID-19 treatment. The collective findings suggest that these compounds possess strong potential as natural antiviral agents. This study highlights compounds 2 and 6 as particularly promising drug leads, warranting further experimental validation through in vitro and in vivo studies to confirm their antiviral activity.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"246"},"PeriodicalIF":0.0,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149066915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated bulk-single-cell transcriptomics identifies IL17RB as a candidate prognostic marker in colon cancer.","authors":"Deborah Oluwaseun Babalola, Xiaoli Sun, Pengchao Deng, Shizhu Jin","doi":"10.1007/s40203-026-00746-w","DOIUrl":"https://doi.org/10.1007/s40203-026-00746-w","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Patients with colon cancer can experience substantially different outcomes despite comparable anatomical stage, highlighting the need for molecular markers that complement conventional clinicopathological risk assessment. The interleukin-17 (IL-17) cytokine family has context-dependent roles in mucosal inflammation and tumour biology, but the prognostic relevance and cellular context of individual IL-17 receptors in colon cancer remain incompletely characterised. A prespecified family-wide analysis of 11 IL-17 ligands and receptors was performed in the GSE39582 Discovery cohort using continuous-expression Cox regression with Benjamini-Hochberg correction. The lead candidate, &lt;i&gt;IL17RB&lt;/i&gt;, was evaluated in the predefined GSE39582 Validation subset and independently in TCGA-COAD, followed by clinical and molecular adjustment, model diagnostics, influence analyses and prognostic-model evaluation. Donor-aware single-cell analysis of GSE178341, exploratory Human Protein Atlas immunohistochemistry and DepMap Public 26Q1 colon adenocarcinoma cell-line analysis were used to characterise the cellular, protein-level and experimental-model context of &lt;i&gt;IL17RB&lt;/i&gt;. &lt;i&gt;IL17RB&lt;/i&gt; showed the strongest overall-survival association in the GSE39582 Discovery cohort (HR per 1-SD increase = 0.780, 95% CI 0.672-0.904; &lt;i&gt;P&lt;/i&gt; &lt; 0.001; q = 0.011). The association was directionally concordant in the predefined Validation subset (HR = 0.722, 95% CI 0.533-0.979; &lt;i&gt;P&lt;/i&gt; = 0.036), although it did not remain significant after family-wide correction (q = 0.122), and was also observed for relapse-free survival. In TCGA-COAD, the simple linear association was weaker, whereas clinically adjusted spline modelling showed significant overall association and non-linearity (&lt;i&gt;P&lt;/i&gt; = 0.003 and &lt;i&gt;P&lt;/i&gt; = 0.005, respectively). Clinical and molecular sensitivity analyses generally retained the direction of association. Addition of &lt;i&gt;IL17RB&lt;/i&gt; produced modest improvements in prognostic-model performance, but confidence intervals around incremental Validation metrics included zero. Donor-aware single-cell analysis localised &lt;i&gt;IL17RB&lt;/i&gt; predominantly to epithelial cells and showed higher expression within an independently annotated tuft-cell cluster. Exploratory HPA assessment showed predominantly low or undetectable IL-17RB protein staining in colon adenocarcinoma, whereas the primary continuous DepMap analysis showed no significant association between &lt;i&gt;IL17RB&lt;/i&gt; and the predefined tuft-cell transcriptional programme. &lt;i&gt;IL17RB&lt;/i&gt; represents a candidate prognostic marker with complementary epithelial and tuft-cell-associated biological context. Its incremental contribution to clinical risk prediction remains modest and requires additional independent validation. Higher &lt;i&gt;IL17RB&lt;/i&gt; expression was associated with favourable survival most consistently in GSE39582, while TCGA-COAD revealed a more complex nonlinear relationship. The combined findings support further pr","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"247"},"PeriodicalIF":0.0,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149066865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An interpretable consensus pipeline for candidate dopamine D2 receptor ligands.","authors":"Sphamandla Mtambo, Hezekiel M Kumalo, Cornelius Cano Ssemakalu","doi":"10.1007/s40203-026-00749-7","DOIUrl":"10.1007/s40203-026-00749-7","url":null,"abstract":"<p><p>Machine learning accelerates GPCR ligand discovery but often lacks interpretability and struggles to generalise to structurally novel chemical space. We present an integrated framework combining ensemble learning, SHAP interpretability, and complementary structure-based analyses to prioritise putative candidates for the dopamine D₂ receptor (DRD2). Models were trained on 1247 curated ChEMBL compounds using Bemis-Murcko scaffold-split validation. Feature ablation showed that Morgan fingerprints alone were sufficient for classification (AUC = 0.910), whereas combined physicochemical descriptors improved regression (R² = 0.606). Random Forest achieved scaffold-split classification AUC = 0.906 ± 0.016, and external PubChem BioAssay validation on non-overlapping compounds achieved AUC = 0.954. SHAP analysis identified nitrogen-containing substructural motifs consistent with Asp3.32 recognition, supporting the canonical DRD2 pharmacophore hypothesis. The pipeline recovered nine known DRD2-active compounds among the top 100 docked DrugBank candidates, corresponding to ≈ 14.6-fold enrichment over random selection. Virtual screening of DrugBank prioritised Roginolisib (DB18088), DB08010, and Bitopertin (DB12426) as putative DRD2 candidates. The near-zero correlation between ML predictions and docking scores (<i>r</i> = 0.090, <i>p</i> = 0.37, <i>n</i> = 100) supports their use as complementary evidence streams. Molecular dynamics simulations (200 ns) and MM-GBSA calculations indicated stable binding modes with geometries distinct from the reference ligand 8NU. By requiring agreement across complementary computational evidence streams, this consensus pipeline provides a reproducible framework for prioritising compounds in extrapolative GPCR chemical space. Experimental validation through radioligand binding and functional assays is required to confirm DRD2 activity.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at https://doi.org/10.1007/s40203-026-00749-7.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"251"},"PeriodicalIF":0.0,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149066837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated network pharmacology, molecular docking, ADMET profiling and In vitro α-amylase inhibitory evaluation of <i>Cardiospermum halicacabum</i> Linn. Against diabetes mellitus.","authors":"Manu B Math, Prakash Dabadi, A M Krupanidhi","doi":"10.1007/s40203-026-00756-8","DOIUrl":"10.1007/s40203-026-00756-8","url":null,"abstract":"<p><p>Diabetes mellitus is a chronic metabolic disorder characterized by impaired glucose homeostasis, insulin resistance, and progressive complications. Although <i>Cardiospermum halicacabum</i> Linn. has demonstrated antihyperglycemic activity in traditional medicine, its molecular mechanisms remain poorly understood. This study investigated its antidiabetic mechanisms using network pharmacology, molecular docking, ADMET profiling, and in vitro α-amylase inhibition. Preliminary phytochemical screening was performed on the ethanolic extract. Phytoconstituents were retrieved from the IMPPAT database and screened for drug-likeness. Potential targets were predicted using SwissTargetPrediction and SuperPred, while diabetes-associated genes were collected from GeneCards and OMIM. Network pharmacology, GO and KEGG enrichment analysis, molecular docking with redocking validation, ADMET prediction, and in vitro α-amylase inhibition assays were conducted. Thirty-seven phytoconstituents, 417 compound-related targets, and 1,025 diabetes-related targets yielded 210 overlapping targets. Apigenin, luteolin, chrysoeriol, kaempferol, and quercetin were identified as principal phytoconstituents, while AKT1, PTPN1, PIK3CA, and MAPK8 emerged as hub targets. KEGG analysis highlighted the AGE-RAGE and MAPK signalling pathways. Apigenin showed the strongest predicted binding affinity toward PIK3CA (- 9.61 kcal/mol). The extract exhibited concentration-dependent α-amylase inhibition, reaching 71.27 ± 1.31% inhibition at 1000 μg/mL, with an IC₅₀ of 218.40 μg/mL, whereas acarbose showed 97.10 ± 0.60% inhibition at 1000 μg/mL, with an IC₅₀ of 62.43 μg/mL. <i>Cardiospermum halicacabum</i> may exert antidiabetic activity through multitarget mechanisms. These findings provide computational evidence supported by preliminary experimental validation; however, further target-specific in vitro, in vivo, and clinical studies are required to confirm the proposed mechanisms.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at https://doi.org/10.1007/s40203-026-00756-8.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"248"},"PeriodicalIF":0.0,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149066924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the interaction landscape of NDM-1 with a novel β-lactam-based inhibitor: implications for rational drug design.","authors":"Saraswathy Nagendran, Sugunadevi Sakkiah","doi":"10.1007/s40203-026-00747-9","DOIUrl":"10.1007/s40203-026-00747-9","url":null,"abstract":"<p><p>The rise of antibiotic resistance mediated by New Delhi metallo-β-lactamase-1 (NDM-1) poses a major challenge to antimicrobial therapy. In this study, structure-based virtual screening, molecular docking, post-docking MM-GBSA rescoring, and 1 μs molecular dynamics (MD) simulations were used to prioritize β-lactam-derived inhibitors of NDM-1. Three compounds were advanced for energetic and dynamic evaluation. Among them, 5YLP_14953 showed the most favorable single-structure Prime MM-GBSA score (- 73.38 kcal/mol). These calculated values are used for relative ranking and should not be interpreted as experimentally measured absolute binding free energies. Interaction and trajectory analyses indicated persistent contacts with the dinuclear Zn²⁺ center and catalytic-site residues, including His122, Asp124, Cys208, and His250. The ligand-bound systems retained stable global folds, while local fluctuations were concentrated mainly in terminal and loop regions. The results support 5YLP_14953, 5YLP_10079, and 5YLP_27558 as computationally prioritized leads for experimental testing. Because the study used one trajectory per complex and did not include apo-NDM-1 or a known-inhibitor control, the conclusions are limited to pose stability and comparative computational prioritization.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"239"},"PeriodicalIF":0.0,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149013487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated metabolite profiling, L-DOPA quantification, antioxidant, anti-inflammatory and computational evaluation of <i>Mucuna pruriens</i> (L.) seeds for neuroprotective applications.","authors":"Sudheendra Rao Kulkarni, Ramesh Babu Yarajarla","doi":"10.1007/s40203-026-00751-z","DOIUrl":"10.1007/s40203-026-00751-z","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a progressive neurodegenerative disorder that features oxidative stress, dopaminergic neuronal degeneration and dysfunction in dopaminergic metabolism. The therapeutic relevance of <i>Mucuna pruriens</i> has been known for a certain period of time in PD. However, there is need of detailed and in-depth studies that involve phytochemical profiling, antioxidant activity, pharmacokinetic assessment, and molecular interaction via in silico. The present study reports the exploration of phytochemistry and computational insights based on <i>Mucuna pruriens'</i> neuro-protective potential. Preliminary visual confirmation of the metabolites assured aqueous extract to contain phenolics, saponins, flavonoids, tannins, catechol, and terpenoids in higher concentration. GC-MS analysis of 5 extracts reported 33 tentative compounds. Catechol, 4-methyl catechol, maltol, pyrogallol, and n-hexadecanoic acid were found to be BBB permeable and pharmacokinetic properties in ADMET. Molecular docking analysis showed favorable ligand-protein interactions with Parkinson's disease-related targets. It includes matrix metalloproteinase-9 (MMP-9) (- 5.012 kcal/mol), adenosine A2A receptor (- 5.026 kcal/mol), and catechol-O-methyltransferase (COMT) (- 5.126 kcal/mol). Catechol exhibits the highest binding affinity toward COMT. Furthermore, molecular dynamics simulations of the catechol-COMT complex (100 ns) demonstrated stable protein-ligand interactions. It showcases a favorable binding conformation throughout the simulation and supports the stability of the docked complex. The antioxidant potential of the extracts was further confirmed by DPPH, ABTS, and FRAP assays. The aqueous extract showed significant free radical scavenging activity, with 84.75% inhibition of DPPH. These findings demonstrate that <i>Mucuna pruriens</i> is a rich source of bioactive phytochemicals with significant antioxidant activity and promising neuroprotective potential. The identified metabolites may help regulate dopaminergic pathway. Further in vitro and in vivo investigations may also reveal their capability in managing PD and related neurodegenerative disorders.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at https://doi.org/10.1007/s40203-026-00751-z.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"243"},"PeriodicalIF":0.0,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149013526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GC-MS profiling, network pharmacology, and computational investigations of canola phytochemicals as potential cardioprotective agents.","authors":"Zohaib Younas, Ilyas Ahmad, Naveed Iqbal Raja, Ashfaq Ahmad, Donald Fernandes, Zia Ur Rehman Mashwani","doi":"10.1007/s40203-026-00744-y","DOIUrl":"10.1007/s40203-026-00744-y","url":null,"abstract":"<p><p><i>Brassica napus</i> L. (canola) is one of the major global sources of edible oil for human nutrition and rich in bioactive compounds with medicinal value. Gamma irradiation treatments (0-30 Gy) were applied to Canola Super-8, NARC-Sarson, Punjab canola, and Sundal canola, resulting in putative annotation of 155 compounds through gas chromatography mass spectroscopy (GC-MS) analysis. By integrating network pharmacology, eight representative compounds were chosen for target prediction, showing 380 common targets among canola-derived metabolites and proteins related to cardiovascular disease (CVD). In the protein-protein interaction network, epidermal growth factor receptor (EGFR) had a degree of 118 and C-terminal domain of human heat shock factor 1 (HSF1) had a degree of 88, reflecting their central hub positions among the common CVD targets. Hydrogen bond and π-π stacking with the amino acid residue forms the oleic acid-C-terminal domain of HSF1 complex, that is stable and exhibits highest binding affinity of - 7.9 kcal/mol, higher than that of standard drug atorvastatin-C-terminal domain of human heat shock factor 1 (HSF1) complex with affinity score of - 7.8 kcal/mol. Molecular dynamics simulation for 100 ns reaffirms the root-mean-square deviation (RMSD) for control and complex to be 1.5 Å, indicating high structural stability. Radius of gyration (RoG) values of 21 and 21.1 Å in the case of control and complex indicates comparable compactness. The protein-ligand complex shows an average solvent accessible surface area (SASA) of 6254.33 Ų and buried surface area (BSA) value of 638.64 Ų. The present study is the first in its ability to enumerate a range of potentially pharmacologically active compounds/bioactive compounds in canola variety seed/seed oil by GC-MS analysis and enunciates a novel nutraceutical approach for the prevention of CVD.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at https://doi.org/10.1007/s40203-026-00744-y.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"240"},"PeriodicalIF":0.0,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149013528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}