In silico pharmacology最新文献

{"title":"Ethnomedicinal plants for pain and inflammation in Malakand Top, Pakistan: an ethnopharmacological and in silico evaluation.","authors":"Majid Khan, Fazli Amin, Muhammad Hassan, Amir Zeb, Najm Ur Rahman, Muhammad Jawad, Abdullah","doi":"10.1007/s40203-026-00752-y","DOIUrl":"10.1007/s40203-026-00752-y","url":null,"abstract":"<p><p>Pain remains one of the most common health concerns worldwide, and medicinal plants continue to play an important role in its traditional management. This study aimed to document and evaluate medicinal plants traditionally used for pain management in the Malakand region of Pakistan using ethnopharmacological approaches. A semi-structured questionnaire survey was conducted across ten villages involving 377 informants. Ethnopharmacological indices, including Relative Frequency of Citation (RFC) and Fidelity Level (FL), were used to assess the importance of reported medicinal plants. Major phytoconstituents from the five most frequently cited species were further subjected to in silico pharmacokinetic and drug-likeness evaluation using the SwissADME web server. A total of 35 medicinal plant species belonging to 27 families were documented. Lamiaceae and Fabaceae were the most represented plant families. Dietary and topical preparations were the predominant modes of administration. The documented plants were used to treat various pain-related conditions, with arthritis (15 species) and stomachache (14 species) being the most frequently reported, followed by toothache, backache, headache, and peripheral pain. <i>Curcuma longa</i> exhibited the highest RFC (0.84) and FL (84.8%), followed by <i>Acacia nilotica, Nigella sativa, Dodonaea viscosa</i>, and <i>Mentha spicata</i>. SwissADME analysis suggested favorable drug-likeness profiles for curcumin, thymoquinone, quercetin, catechin, and limonene, with all compounds satisfying Lipinski's rule of five and had a predicted bioavailability score of 0.55. The BOILED-Egg model further predicted blood-brain barrier permeability for thymoquinone and limonene. The study highlights the rich ethnomedicinal knowledge of the Malakand region and identifies several promising plant species used in traditional pain management. In silico analysis provided preliminary support for the pharmacokinetic suitability of major phytoconstituents, warranting further experimental and clinical investigations. Conservation strategies are recommended to preserve these valuable medicinal resources.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"241"},"PeriodicalIF":0.0,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149013461","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":"Design, synthesis and in silico evaluation of quinoline-indole chalcone hybrids for potential antibacterial, anticancer and antineurodegenerative applications.","authors":"Swetha Manjunathaiah, HemanthKumar Dharmapuri, Madhushree B N, Anchal Singhal","doi":"10.1007/s40203-026-00735-z","DOIUrl":"10.1007/s40203-026-00735-z","url":null,"abstract":"<p><p>This investigation centres on the design, synthesis and computational evaluation of novel N-heterocyclic hybrid molecules that possess three-in-one functionalities: quinoline-indole chalcone (QIC). These hybrids have been successfully synthesized using Claisen-Schmidt condensation reaction between 3-acetyl-2-methyl-4-phenylquinoline <b>(3a)</b> (AcQ)/ 1-(6-bromo-2-methyl-4-phenylquinolin-3-yl)ethan-1-one (B-AcQ) <b>(3b)</b> and indole-3-aldehyde <b>(4a-e)</b> precursors. Structural integrity and purity of all the compounds were confirmed by ¹H-NMR, ¹³C-NMR, FTIR, HRMS and HPLC. The computational study was executed using ADMETlab 3.0 online tool favoring drug-likeness and pharmacokinetic properties for all the compounds, adhering to Lipinski's Rule of Five. Molecular docking was performed using key protein targets to evaluate antibacterial <i>(PDB IDs: 3TTZ</i> and <i>7C7O)</i>, anticancer <i>(PDB IDs: 4HJO</i> and <i>3W2S)</i> and antineurodegenerative <i>(PDB IDs: 2V5Z</i> and <i>2Z5X)</i> properties of all the synthesized compounds. The results indicated stronger binding interactions of <b>5f (- 11.86 kcal/mol)</b> and <b>5g (- 9.71 kcal/mol)</b> with antibacterial, <b>5d (- 11.89 kcal/mol) and 5h (- 11.72 kcal/mol)</b> with anticancer and <b> 5h (- 14.89 kcal/mol)</b> and <b>5a (- 8.53 kcal/mol)</b> with antineurodegenerative protein targets compared with the co-crystal ligands <b>07N</b> and <b>FKU</b> for antibacterial <b>(- 8.67 kcal/mol and - 10.95 kcal/mol) respectively</b>, co-crystal ligand <b>W2R (- 13.73 kcal/mol)</b> and <b>reference drug erlotinib (- 7.87 kcal/mol)</b> for anticancer, <b>safinamide (- 9.64 kcal/mol)</b> and <b>harmine</b> <b>(- 7.61 kcal/mol)</b> for antineurodegenerative targets. These compounds showed comparable or stronger predicted binding affinities under the applied docking conditions.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at https://doi.org/10.1007/s40203-026-00735-z.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"242"},"PeriodicalIF":0.0,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149013458","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 metabolomics and molecular dynamics simulation reveals moupinamide and echitoserpidine as promising neuroprotective scaffolds from <i>Persea americana</i> seed extract.","authors":"Yusuf Salami, Holiness Stephen Adedeji Olasore, Osaretin Albert Taiwo Ebuehi","doi":"10.1007/s40203-026-00739-9","DOIUrl":"10.1007/s40203-026-00739-9","url":null,"abstract":"<p><p>Neurodegenerative diseases represent a growing global health burden, largely driven by population ageing and the absence of disease-modifying therapies. Current treatment strategies remain largely symptomatic, highlighting the need for the identification of novel neuroprotective agents targeting key pathological mechanisms such as impaired proteostasis and dysregulated signalling pathways. In this study, an integrated in silico workflow was employed to investigate LC-MS-annotated metabolites from <i>Persea americana</i> (avocado) seed extract for their binding interactions with two neurodegeneration-related protein targets, GPR52 and UCHL1. Untargeted LC-MS profiling was followed by metabolite annotation, target prediction, molecular docking, molecular dynamics (MD) simulations (50 ns for GPR52 and 100 ns for UCHL1), and binding free energy calculations using MM/GBSA and MM/PBSA approaches. Among LC-MS-putatively identified metabolites, moupinamide and echitoserpidine showed stable binding across molecular dynamics simulations, supported by consistent structural stability and favourable binding free energies against GPR52 and UCHL1 respectively. In contrast, scoulerine and piperine exhibited less favourable MM/PBSA binding free energies despite their moderate docking scores, indicating weaker predicted binding affinity. ADMET analysis revealed generally acceptable drug-like properties, but limitations in pharmacokinetics and central nervous system accessibility, particularly blood-brain barrier permeability, cardiotoxicity and metabolic stability. Overall, the results suggest that LC-MS-annotated metabolites from <i>Persea americana</i> seed extract may represent potential candidates for further investigation as modulators of GPR52 and UCHL1, with moupinamide and echitoserpidine emerging as the most promising scaffolds among the evaluated metabolites based on integrated docking, molecular dynamics, and binding free-energy analyses. However, further structural optimization and experimental validation are required to confirm their biological relevance and assess their suitability for neurodegeneration-related drug discovery.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"244"},"PeriodicalIF":0.0,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149013506","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":"Computational engineering of the scorpion venom peptide Ttap3 enhances membrane selectivity and antimicrobial potential.","authors":"Stephenson Obeng Owusu, Sharifa Fatao, Michael Konney Laryea, Cedric Dzidzor Kodjo Amengor, Lawrence Sheringham Borquaye","doi":"10.1007/s40203-026-00742-0","DOIUrl":"10.1007/s40203-026-00742-0","url":null,"abstract":"<p><strong>Abstract: </strong>Venom-derived antimicrobial peptides (AMPs) are promising scaffolds for next-generation antimicrobial agents because of their structural diversity and membrane-targeting mechanisms. Ttap3, a peptide isolated from scorpion venom, exhibits weak antimicrobial activity despite possessing characteristic amphipathic features associated with membrane-active peptides. This study employed a computational engineering strategy to redesign Ttap3 and investigate how sequence modifications influence membrane selectivity and antimicrobial potential. Structural modelling showed that Ttap3 adopted a predominantly α-helical amphipathic conformation with moderate hydrophobic moment and relatively high hydrophobicity. Molecular dynamics simulations demonstrated preferential interaction with bacterial membrane models relative to mammalian membranes, although measurable interaction with mammalian bilayers was also observed. Rational sequence modifications involving residue substitution, sequence reversal, and modulation of amphipathicity and flexibility generated analogues with improved predicted selectivity profiles. Multi-scale molecular dynamics simulations revealed distinct membrane interaction behaviours among the redesigned analogues, including surface-associated destabilization, localized pore formation, and insertion-driven membrane perturbation. Coordinated membrane disruption involving hydrogen bond loss, lipid disorder, phospholipid deflection, altered pore radii, and increased water influx was observed predominantly in bacterial membrane systems. Partial reduction in peptide helicity during membrane interaction also appeared to contribute to selective membrane destabilization. These findings demonstrate that rational computational redesign can substantially improve the predicted antimicrobial potential and membrane selectivity of weakly active venom-derived peptides.</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/s40203-026-00742-0.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"237"},"PeriodicalIF":0.0,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13582730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148993228","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 molecular docking, simulation dynamics and cytotoxicity assays of <i>Desmodium gangeticum</i>-derived phytochemicals for multi-target cancer therapy.","authors":"Baably Swayamsidha, Shubhranshee Sanshlishta Sahu, Animesh Pattnaik, Rukmini Mishra, Raj Kumar Joshi","doi":"10.1007/s40203-026-00748-8","DOIUrl":"10.1007/s40203-026-00748-8","url":null,"abstract":"<p><p>Cancer continues to be a significant worldwide health concern, requiring ongoing research into new and efficient treatment options. This study used an integrated in-vitro and in-silico strategy to systematically examine the anticancer potential of phytoconstituents produced by <i>Desmodium gangeticum</i> (Linn.). Using phytochemicals found in the root and shoot extracts, molecular docking investigations were carried out against three important cancer-associated targets: BCL-XL, translocator protein (TSPO), and tubulin. With docking scores of - 7.27 and - 8.15, respectively, squalene and benzenamine, 4,4'-ethylidenebis [N, N-diethyl-3-methyl-], showed significant binding affinities toward BCL-XL, TSPO, and tubulin among the root-derived compounds. From among the shoot-derived compounds, stigmasterol had the highest affinity for TSPO (- 11.81 kcal/mol) and tubulin (- 8.17 kcal/mol), while γ-sitosterol showed the strongest binding association with BCL-XL (- 9.39 kcal/mol). BIOVIA Discovery Studio was used to visualise protein-ligand interactions, and SwissADME was used to assess the lead compounds' drug-likeness and pharmacokinetic profiles in compliance with Lipinski and Veber's guidelines. The stability and conformational flexibility of the γ-sitosterol protein complexes throughout a 50-ns trajectory were further validated by molecular dynamics simulations. The chloroform root extract showed the highest antiproliferative activity against OVCAR-3 and HeLa cancer cell lines. Collectively, these findings highlight <i>D. gangeticum</i> as a promising source of bioactive compounds with significant anticancer potential, warranting further mechanistic and preclinical investigations.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at https://doi.org/10.1007/s40203-026-00748-8.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"238"},"PeriodicalIF":0.0,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13582687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148993250","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 investigation and identification of potential phytocompounds targeting dengue virus NS5 methyltransferase.","authors":"Sumiya Ahmad Sejuti, Mijan Mia, Apurbo Pal, Ahsan Habib","doi":"10.1007/s40203-026-00723-3","DOIUrl":"10.1007/s40203-026-00723-3","url":null,"abstract":"<p><p>Dengue is an escalating public health threat in warm climate zones, particularly in tropical and subtropical regions. The World Health Organization (WHO) recorded approximately 4 million cases and 3000 deaths in 97 countries between January and July 2025, highlighting the urgent need for effective antiviral therapeutics. The presence of four genetically distinct serotypes of dengue virus (DENV) and the lack of a broadly effective drug pose major challenges for disease control. This study utilized an in silico approach to suggest potential phytocompounds targeting the non-structural protein 5 (NS5) methyltransferase, a crucial protein involved in 5'-mRNA capping. A total of 605 phytocompounds from <i>Allium sativum, Curcuma longa, Camellia sinensis,</i> and <i>Carica papaya</i> were screened based on Lipinski's rule of five and docked against the NS5 methyltransferase protein. Eight compounds exhibited higher predicted binding affinities than the control (-7.648 kcal/mol) with Dehydrocarpaine-I showing the most favorable predicted binding affinities (-9.456 kcal/mol). Top candidates were further evaluated based on their pharmacokinetic properties, toxicity profiles, and the protein-ligand interactions. Molecular dynamics simulations and principal component analysis (PCA) suggested the stability and favorable dynamic behavior of Dehydrocarpaine-I, Theasapogenol-B, and Brassinolide. MM-PBSA calculations showed that Theasapogenol-B (-62.48 kcal/mol) and Brassinolide (-44.82 kcal/mol) exhibited more favorable binding free energies compared to the control (-43.46 kcal/mol). This study suggests Theasapogenol-B and Brassinolide as potential lead compounds targeting NS5 methyltransferase and provides a basis for further comprehensive in silico, in vitro and in vivo validation.</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/s40203-026-00723-3.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"236"},"PeriodicalIF":0.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13575057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148979164","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":"Enhanced antioxidant and anti-inflammatory activities of BerbiQ compared with berberine and silymarin: integrated in vitro and in silico investigations.","authors":"V Anantha Bhairavi, V Anantha Narayanan, Sreelakshmi Aravind Kuppadakath, Ardra Das, Augustine Amalraj, Sreeraj Gopi","doi":"10.1007/s40203-026-00733-1","DOIUrl":"10.1007/s40203-026-00733-1","url":null,"abstract":"<p><p>Berberine is a bioactive isoquinoline alkaloid with reported antioxidant and anti-inflammatory properties, however, its therapeutic application is limited by poor solubility and bioavailability. BerbiQ is a novel OMICS technology based berberine formulation developed through complexation with silymarin and coconut derived lipid protein matrices to enhance the solubility, stability, bioavailability and biological efficacy of berberine. This study comparatively evaluated the biological activities of berberine, silymarin and its formulation BerbiQ using integrated in vitro and in silico approaches. Antioxidant activity was assessed with 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, while anti-inflammatory activity was evaluated in RAW 264.7 macrophages through nitric oxide, lipoxygenase and cyclooxygenase inhibitory assays. In silico molecular docking and molecular dynamics simulations were performed to investigate the interactions of berberine and silymarin with Kelch-like ECH-associated protein 1 (keap1) and inducible nitric oxide synthase (iNOS), key targets associated with oxidative stress and inflammatory signaling pathways. Antioxidant evaluation revealed that BerbiQ exhibited enhanced radical scavenging activity compared with berberine and silymarin. All test samples demonstrated concentration-dependent anti-inflammatory activity in RAW 264.7 macrophages, with BerbiQ exhibiting comparatively higher inhibitory activity against anti-inflammatory pathways. Computational analyses further demonstrated favourable binding affinities and stable interaction profiles of berberine and silymarin with keap1 and iNOS, supporting their potential modulatory effects on oxidative stress and inflammatory responses. Collectively, the findings demonstrate that BerbiQ preserves the intrinsic pharmacological properties of berberine by combining with silymarin while enhancing its antioxidant and anti-inflammatory efficacy. The study highlights the importance of advanced formulation strategies in improving the biological and therapeutic potential of natural bioactive compounds.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"234"},"PeriodicalIF":0.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13575084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148979162","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 analysis of MALAT1 and H19 lncRNA interactions with the diabetes-related proteins ASK1 and YAP1.","authors":"Leonardo Elías Cabrera-Nájera, Olga Nelly Rodríguez-Peña, Cesar Mateo Flores-Ortíz, Martín Palomar-Morales","doi":"10.1007/s40203-026-00734-0","DOIUrl":"10.1007/s40203-026-00734-0","url":null,"abstract":"<p><p>Dysregulation of RNA-protein signalling networks contributes to the progression of diabetes-associated complications, yet the structural mechanisms underlying lncRNA interactions with key signalling proteins remain largely unknown. This study investigates potential interaction interfaces between MALAT1-ASK1 and H19-YAP1 using a hypothesis-generating in silico approach. A computational pipeline integrating structure prediction, molecular docking, and molecular dynamics simulations was employed. Structural assessment showed high local confidence for both proteins and lncRNAs (PAE < 1 Å) but low global lncRNA folding reliability (pTM < 0.5), consistent with intrinsic structural flexibility. ASK1 and YAP1 exhibited multiple surface cavities and disordered regions involved in signalling regulation. Docking and simulations suggested MALAT1 binding to exposed ASK1 surfaces, while H19 was predicted to associate with YAP1 regions encompassing the TEAD-binding domain and conserved regulatory phosphorylation sites, including residues corresponding to Ser109, Ser127, and Thr119. Molecular dynamics indicated transient stabilisation with persistent conformational heterogeneity. These results identify structurally plausible RNA-protein interaction interfaces that overlap with known regulatory hotspots in YAP1. Overall, this work provides a framework for experimental validation of lncRNA-mediated regulation in diabetes-related signalling pathways.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"235"},"PeriodicalIF":0.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13575055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148979194","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":"Computational prediction of flavonoid inhibitors targeting the infectious bronchitis virus spike protein through integrated virtual screening and molecular dynamics.","authors":"Irfan Gul, Sadaf Bashir, Muttahir Aman, Amreena Hassan, Muzamil Ahmad Rather, Ubaid Sofi, Naveed Anjum Chikan, Nadeem Shabir","doi":"10.1007/s40203-026-00727-z","DOIUrl":"10.1007/s40203-026-00727-z","url":null,"abstract":"<p><p>Infectious bronchitis virus (IBV) remains a major threat to the poultry industry owing to its high transmissibility and the continuous emergence of antigenically diverse variants that compromise vaccine efficacy. The viral spike protein, which mediates host cell attachment and membrane fusion, represents an attractive target for antiviral intervention. In this study, a structure-based computational approach was employed to identify phytochemical inhibitors targeting the IBV spike protein. A curated library (PCLibVer2) comprising 2,400 phytochemicals derived from poultry-safe botanicals was subjected to hierarchical virtual screening using Glide against two receptor-binding domain-associated binding pockets. The three top-ranked lead phytochemicals were evaluated by three independent 100 ns molecular dynamics simulations, followed by trajectory-based Prime MM-GBSA binding free energy calculations and principal component analysis. All three phytochemicals exhibited favourable docking scores and stable protein-ligand interactions throughout the simulations. Molecular dynamics analyses demonstrated stable structural behaviour, persistent hydrogen-bond interactions, and reduced conformational sampling relative to the apo protein. MM-GBSA analysis predicted favourable binding free energies for all complexes, with Rutin exhibiting the strongest binding affinity at both binding pockets (- 50.07 ± 13.14 and - 55.14 ± 20.22 kcal/mol). Principal component analysis further showed that Rutin consistently produced the most compact conformational ensemble, indicating reduced protein flexibility. In silico ADMET analysis identified comparable pharmacokinetic profiles for the three lead phytochemicals. Collectively, these findings highlight the potential of flavonoid-based phytochemicals as natural inhibitors of IBV spike-mediated viral entry. This study provides a computational framework for the development of phytochemical-based interventions that may complement existing vaccination strategies and support efforts to reduce antibiotic use in poultry, pending experimental validation.</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/s40203-026-00727-z.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"222"},"PeriodicalIF":0.0,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13547205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148908406","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":"Can docking-score differences support 5-HT2A/5-HT2B subtype-selectivity decisions? An audited paired benchmark.","authors":"Sen Ye","doi":"10.1007/s40203-026-00745-x","DOIUrl":"10.1007/s40203-026-00745-x","url":null,"abstract":"<p><p>Subtype selectivity is a paired drug-design property, and some structure-based studies infer it from score comparisons across receptors without directly validating the score difference against paired experimental selectivity. We evaluated Vina-family docking-score differences in an audited 5-HT2A/5-HT2B benchmark comprising 419 same-endpoint paired activity records, 413 unique compounds, and 411 docking-complete compounds across two structures per subtype. Experimental selectivity was ΔpX = pX(5-HT2A) - pX(5-HT2B), and docking selectivity was Δscore = mean score(5-HT2B) - mean score(5-HT2A), so positive values favored 5-HT2A. Vina Δscore gave Pearson <i>r</i> = 0.097 (95% confidence interval 0.020 to 0.173) and Spearman ρ = 0.057 (95% confidence interval - 0.039 to 0.151); both intervals lay below the predefined |r| = 0.20 practical threshold. Strong-selectivity discrimination gave an area under the receiver-operating-characteristic curve of 0.544 (95% confidence interval 0.427 to 0.664). The continuous association weakened with alternative scoring and disappeared after full Vinardo redocking. Under scaffold cross-validation, descriptor-plus-docking was indistinguishable from its ligand-only baseline. Fingerprint-plus-docking reduced error by 0.037 pX (ΔRMSE = - 0.037, 95% confidence interval - 0.051 to - 0.023); the point estimate was below the 0.05 pX practical threshold, although the interval narrowly reached it. Within this fixed, ligand-context-asymmetric, non-transducer-bound four-structure benchmark, Vina-family score-level features provide hypothesis-generating evidence rather than convincing stand-alone support for 5-HT2A/5-HT2B selectivity decisions.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at https://doi.org/10.1007/s40203-026-00745-x.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"230"},"PeriodicalIF":0.0,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13547201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148908418","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}