In silico pharmacology最新文献

{"title":"Integrated molecular docking, toxicity prediction, and molecular dynamics simulations studies to identify potential antimalarial candidates targeting enoyl-acyl carrier protein reductase enzyme.","authors":"Abozur Mohamed Mohyeldin Khalil, Carlos Eliel Maya-Ramírez, Ammar A Razzak Mahmood, Ebaa Mohammed Alfatih Ahmed, Mosab Yahya Al-Nour, Bashir A Yousef","doi":"10.1007/s40203-026-00637-0","DOIUrl":"https://doi.org/10.1007/s40203-026-00637-0","url":null,"abstract":"<p><p>Malaria remains a life-threatening disease, and the emergence of drug-resistant Plasmodium falciparum highlights the urgent need for new antimalarial agents. Targeting enoyl-acyl carrier protein reductase (ENR), a key enzyme in the parasite's fatty acid synthesis pathway, offers a promising strategy for drug development. In this study, an integrated in silico approach was employed to identify potential ENR inhibitors from the Life Chemicals' Plasmodium Focused Library (7,900 compounds). Virtual screening was performed using Glide, followed by pharmacokinetic and toxicity prediction with pkCSM and ProTox 3.0, and molecular dynamics (MD) simulations with Desmond. The top five compounds-Cd3, Cd5, Cd7, Cd8, and Cd9-demonstrated favorable binding affinities and drug-like properties. Cd3 (docking score: -9.15) exhibited 100% intestinal absorption, favorable volume of distribution, moderate clearance, and higher predicted binding stability (RMSD < 3 Å) compared to Triclosan, the reference inhibitor. Toxicity predictions indicated potential hepatotoxicity, neurotoxicity, immunotoxicity, and respiratory toxicity for the top candidates, suggesting the need for structural optimization. Based on their overall pharmacokinetic and safety profiles, Cd3 and Cd5 are highlighted as the most promising candidates for further development. In vitro validation studies are recommended toconfirm binding affinities and antimalarial efficacy. This study demonstrates a cost-effective computational workflow for prioritizing ENR inhibitors, providing a foundation for the development of novel antimalarial agents.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"210"},"PeriodicalIF":0.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803450","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":"Exploring the anti-<i>Helicobacter pylori</i> activity of Guluchyadi Kashayam through in-vitro and in-silico analysis.","authors":"Priya Venugopal, Abel John Koshy, Anuroopa G Nadh, Sini S Raj, Rajesh Raju, Amjesh Revikumar","doi":"10.1007/s40203-026-00709-1","DOIUrl":"https://doi.org/10.1007/s40203-026-00709-1","url":null,"abstract":"<p><p><i>Helicobacter pylori</i> infection, a driver of chronic gastritis and gastric cancer, requires new therapeutic strategies due to rising antibiotic resistance. Guluchyadi Kashayam, a traditional Ayurvedic formulation, serves as a potential source of anti-<i>H. pylori</i> compounds. Anti-<i>H. pylori</i> activity was evaluated using solvent-fractionated extracts and in vitro assays. GC-MS-identified constituents were screened for ADME properties. Promising compounds underwent molecular docking against essential <i>H. pylori</i> proteins, with lead complexes analyzed via 200 ns molecular dynamics simulations and MM/GBSA calculations. Multiple solvent fractions showed inhibitory activity. GC-MS identified 129 phytochemicals, with four showing favorable ADME profiles. Molecular docking identified Benzenemethanimine, <i>N</i>-(1,1-dimethylethyl)-α-[(formylamino)methyl]-4-methyl- (CID: 546407) as the top candidate, demonstrating high affinity for the β-clamp protein (docking: - 7.479 kcal/mol; MM/GBSA ΔGbind: - 32.94 kcal/mol). Molecular dynamics and MM-GBSA analyses identified it as the sole viable lead (ΔG = - 10.94 kcal/mol). Driven by robust Van der Waals forces, it avoids the massive entropic penalties hindering other compounds. Structurally, it induces a stable, highly compact, yet uniquely solvent-exposed conformation without triggering localized flexibility disruptions. This study supports the anti-<i>H. pylori</i> potential of Guluchyadi Kashayam. We identify the β-clamp protein as a therapeutic target and CID 546,407 as a promising lead for drug development.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-026-00709-1.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"213"},"PeriodicalIF":0.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803489","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":"Replicated molecular dynamics of five natural products at the human Keap1 ETGE pocket prioritises catalpol and geniposide for experimental validation.","authors":"Byungwoong Yoo","doi":"10.1007/s40203-026-00724-2","DOIUrl":"https://doi.org/10.1007/s40203-026-00724-2","url":null,"abstract":"<p><p>The Keap1-Nrf2-ARE pathway coordinates cellular antioxidant defence and is a potential target for limiting oxidative and neuroinflammatory injury. Natural products can activate Nrf2 through several mechanisms, but persistent non-covalent occupancy of the Keap1 ETGE pocket has rarely been demonstrated experimentally. We compared catalpol, geniposide, loganin, morroniside and coptisine using a uniform workflow based on docking to the human Keap1 Kelch domain, independently replicated all-atom molecular dynamics, and conformational and interaction analyses for the full panel; a quality-controlled endpoint-energy sensitivity check was restricted to the reproducibly retained catalpol and geniposide complexes. Protein compactness, correlated Cα motions, conformational probability density, ligand displacement, pocket contacts, hydrogen bonding, solvent burial and anchor-residue behaviour were assessed across replicates. Catalpol and geniposide were retained most reproducibly near the ETGE pocket, whereas loganin showed heterogeneous excursions, morroniside was not reproducibly retained and coptisine was consistently displaced. Global Keap1 conformational sampling remained compact, and the dominant cross-correlation patterns were shared across retained and non-retained complexes; without an apo control, these patterns do not support ligand-specific allosteric inference. The preliminary prioritisation of morroniside was therefore not reproduced. These findings identify catalpol and geniposide as computational candidates, not experimentally established Keap1 binders or Nrf2 activators through pocket competition. Direct-binding and ETGE-peptide competition assays, followed by cellular target-engagement and pathway studies, are required to test the proposed mechanism and its neuroprotective relevance.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-026-00724-2.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"211"},"PeriodicalIF":0.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803517","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":"Structure-based discovery of novel ROCK2 inhibitors using integrated virtual screening, molecular dynamics, metadynamics and absolute binding free energy calculations.","authors":"Shradheya R R Gupta, Rashmi Rameshwari, Indrakant K Singh, Vanshika Rustagi","doi":"10.1007/s40203-026-00714-4","DOIUrl":"https://doi.org/10.1007/s40203-026-00714-4","url":null,"abstract":"<p><p>Breast cancer remains one of the most prevalent and deadly malignancies in women globally, with metastasis and invasion contributing significantly to its poor prognosis. Rho-associated kinase 2 (ROCK2), a key regulator in the Ras homolog family member (Rho) GTPase signaling pathway, is implicated in tumor progression and cytoskeletal remodeling, making it an attractive therapeutic target. This study presents a structure-based computational strategy to identify and characterize novel ROCK2 inhibitors. An integrated pipeline involving virtual screening of over 1.5 million compounds focused on heterocyclic scaffolds chosen for their structural compatibility. Promising candidates were refined using MM/GBSA rescoring and molecular dynamics simulations. Conformational stability was assessed through principal component analysis and free energy landscape mapping, while well-tempered metadynamics simulations provided detailed free energy surface profiles. Binding affinities were estimated via Absolute Binding Free Energy Perturbation (ABFEP) calculations. Two lead compounds, ASN52 and Selles74, were identified with synthetically tractable heterocyclic cores and demonstrated strong, stable interactions within the ROCK2 active site. ASN52 exhibited a pronounced energetic minimum at 4 Å (- 11 kcal/mol), indicating a highly favorable binding conformation. ABFEP binding free energies of - 6.7 ± 1.27 kcal/mol (ASN52) and 6.15 ± 1.78 kcal/mol (Selles74) further supported their potential as effective ROCK2 inhibitors. These findings provide a computational foundation for the rational design and preclinical development of ROCK2-targeted therapeutics. The approach and results are applicable to the discovery of both small-molecule and peptidomimetic inhibitors, supporting broader efforts in structure-guided drug design targeting kinases involved in cancer and other diseases.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-026-00714-4.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"216"},"PeriodicalIF":0.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803570","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":"Beyond gluten-free diet: repurposing pitavastatin and lubiprostone as cathepsin S inhibitors for celiac disease therapy.","authors":"Rahul Soloman Singh, Gladson David Masih, Ashutosh Singh, Benjamin Suroy, Gitika Batra, Shiv Charan, Ajay Prakash, Bikash Medhi","doi":"10.1007/s40203-026-00648-x","DOIUrl":"https://doi.org/10.1007/s40203-026-00648-x","url":null,"abstract":"<p><p>Celiac disease is an autoimmune enteropathy associated with the dietary protein, gluten, and affects specific populations carrying genes HLADQ2/8. Currently, the only available treatment is a lifelong gluten-free diet (GFD), and even when following a stringent GFD, about 30% of patients still have symptoms. Another important protein, Cathepsin S, specifically processes gluten proteins for presentation to these MHCs and is therefore a potential target for the disease. The study aims to use a drug repurposing or repositioning strategy to identify a potential Cathepsin S (CatS) inhibitor via a structure-based virtual screening method in drug discovery. The crystal structure of human CatS (PDB: 4P6G) was prepared using Schrödinger Suite and validated through PROCHECK analysis. Virtual screening was performed on 1,615 FDA-approved small molecules from the ZINC15 database using the Glide hierarchical workflow (HTVS, SP, and XP). Lead compounds were evaluated using MM-GBSA binding energy calculations, 100-ns molecular dynamics simulations with Desmond, and ADME property predictions with QikProp. With a docking score of - 9.396 kcal/mol and an MM-GBSA binding energy of - 53.09 kcal/mol, Pitavastatin (ZINC000001534965) was the top-ranked FDA-approved drug according to virtual screening. The second top-ranked compound was Lubiprostone (ZINC000004217732), with a docking score of - 8.935 kcal/mol and an MMGBSA binding energy of - 33.85 kcal/mol. Compared with the co-crystallised reference inhibitor 2FZ (- 7.920 kcal/mol), both compounds exhibited significantly improved binding affinity. Protein-ligand interactions were stable with RMSD values < 2.0 Å over 100 ns trajectories, according to molecular dynamics simulations (Pitavastatin: 1.31 ± 0.37 Å; Lubiprostone: 1.86 ± 0.32 Å). Both compounds exhibited excellent ADME profiles, characterised by favourable lipophilicity and adherence to Lipinski's rule of five, with expected oral absorption exceeding 85% in humans. A focused screening of FDA-approved drugs identified pitavastatin and lubiprostone as promising cathepsin S inhibitors for CeD therapy. Established safety profiles and well-established pharmacokinetics are just a few of the substantial advantages these medicines offer for clinical translation.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"209"},"PeriodicalIF":0.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803395","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":"Enhancing renal tuberculosis treatment: lysozyme-mediated targeted drug delivery approaches.","authors":"Harshita Sonar, Prokriti Paul, Sanchaita Rajkhowa, Borakha Bura Gohain, Manasi Bora","doi":"10.1007/s40203-026-00691-8","DOIUrl":"10.1007/s40203-026-00691-8","url":null,"abstract":"<p><p>Renal tuberculosis (TB) is an extrapulmonary form of TB, and is becoming more common and challenging to treat. This is because many anti-tubercular drugs have nephrotoxicity and have poor drug penetration into renal tissues. These problems highlight the urgent need for safer, kidney-targeted treatment regimes, particularly in patients with compromised kidney function. Thus, this study investigates lysozyme, which is a low-molecular-weight protein and has natural kidney-affinity, as a potential carrier for targeted renal drug delivery. Here, a comprehensive <i>in silico</i> approach has been utilized to identify non-nephrotoxic anti-TB drugs and evaluate their suitability for lysozyme-mediated renal-targeted delivery. For this study, a total of 21 clinically important anti-TB drugs, including first-line, second-line, and newly developed agents, were screened for nephrotoxicity using the SA-Predictor and ProTox 3.0 tools. Of these, eight drugs were predicted to be non-nephrotoxic and were used for molecular docking studies with hen egg-white lysozyme (HEWL). The non-nephrotoxic anti-TB drugs which showed better binding with HEWL, were subjected to 100 ns molecular dynamics simulations to examine protein-drug complex stability and were assessed using RMSD, RMSF, hydrogen-bond occupancy, and radius of gyration. Our study showed that ethambutol, pretomanid, and terizidone demonstrated the most stable interactions with HEWL. This work establishes a systematic computational pipeline that integrates nephrotoxicity profiling, molecular docking, and MD simulations to identify safe anti-TB drugs suitable for renal-targeted delivery. Additionally, in vitro and in vivo validation will be essential for advancing these findings toward clinical application.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-026-00691-8.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 2","pages":"197"},"PeriodicalIF":0.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655454","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":"On neighborhood degree sum-based indices of Nirmatrelvir and its QSPR investigation with some other COVID-19 drugs.","authors":"Shibsankar Das, Arti Kumari","doi":"10.1007/s40203-026-00663-y","DOIUrl":"10.1007/s40203-026-00663-y","url":null,"abstract":"<p><p>Chemical graph theory is a branch of mathematical chemistry that combines chemistry and graph theory. In this field, the topological index is a helpful tool for comprehending physicochemical properties and forecasting the behavior of chemical molecules. The COVID-19 pandemic has underscored the urgent need for effective antiviral therapeutics. Nirmatrelvir, an orally bioavailable SARS-CoV-2 main protease ([Formula: see text]) inhibitor co-administered with Ritonavir (Paxlovid), has emerged as a promising treatment. In this study, we present a detailed topological characterization of Nirmatrelvir by deriving several neighborhood degree sum-based topological indices using its NM-polynomial. Furthermore, we present the QSPR analysis using curvilinear regression models among the obtained topological indices and physicochemical properties of the antiviral COVID-19 drugs, such as Molnupiravir, Arbidol, Chloroquine, Hydroxychloroquine, Thalidomide, Remdesivir, Ritonavir, Theaflavin and Lopinavir, including Nirmatrelvir. The results reveal that several considered indices show significant correlations with the physicochemical properties and cubic regression models consistently provide superior predictive accuracy. These findings demonstrate neighborhood degree sum-based topological indices as robust and reliable molecular descriptors in QSPR modelling, highlighting their significant potential for effective prediction of drug properties and their valuable role in facilitating rational drug design and development.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 2","pages":"198"},"PeriodicalIF":0.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655500","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":"Anti-nociceptive property of thymol: animal study with molecular docking and MD simulation studies.","authors":"Rokibul Islam Chowdhury, Mehedi Hasan Bappi, Shoyaeb Ahammed, Md Sabbir Hossain, Md Showkath Akbor, Md Emon, Armanul Islam, Abdullah Al Shamsh Prottay, Naznin Shahria, Faisal H Altemani, Carolina Bandeira Domiciano, Henrique Douglas Melo Coutinho, Md Torequl Islam","doi":"10.1007/s40203-026-00713-5","DOIUrl":"10.1007/s40203-026-00713-5","url":null,"abstract":"<p><p>Nociceptive pain is a physiological response to tissue injury that activates peripheral and central pain pathways. Thymol (THY) has been reported to possess various pharmacological activities, including potential analgesic effects. In this study, we investigated the anti-nociceptive activity of THY and explored its possible interaction with cyclooxygenase (COX) enzymes using both in vivo and in silico approaches. 60 Swiss albino mice were randomly divided into experimental groups (<i>n</i> = 5 per group) and administered THY orally at doses of 15, 30, and 60 mg/kg. The anti-nociceptive effects were evaluated using the acetic acid-induced writhing test and the hot plate test. Diclofenac sodium (Di-Na) (10 mg/kg) was used as the standard reference drug, while distilled water served as the vehicle control. In addition, molecular docking studies were performed to predict the binding affinity of THY and diclofenac sodium toward COX-1 and COX-2 enzymes, and ligand-receptor interactions were visualized using computational tools. The results demonstrated that THY produced a dose-dependent reduction in nociceptive responses in both experimental models compared to the control group. In silico analysis showed that THY exhibited binding affinities of - 6.3 kcal/mol with COX-1 and COX-2, forming hydrogen bond interactions with the binding site of both enzymes. MD simulation results indicated that the THY-COX complexes remained stable throughout the simulation period, supporting the plausibility of these predicted interactions. Overall, THY showed significant anti-nociceptive activity in vivo, while computational results suggest potential interaction with COX enzymes. However, further biochemical and mechanistic studies are required to confirm its exact mode of action.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 2","pages":"207"},"PeriodicalIF":0.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655293","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 data mining, network pharmacology and molecular docking to explore the medication rules and mechanism of traditional Chinese medicine compound in the treatment of acne.","authors":"Wanyun Zhu, Ziyan Cheng, Qimei Xie, Bin Sun, Min Wei, Songfeng Wang, Yiyun Qian, Pingping Song","doi":"10.1007/s40203-026-00702-8","DOIUrl":"10.1007/s40203-026-00702-8","url":null,"abstract":"<p><p>Through data mining of traditional Chinese medicine (TCM) formulas for acne, high-frequency herbs were identified, including <i>Glycyrrhizae Radix et Rhizoma</i> (gancao, GC)<i>, Scutellariae Radix</i> (huangqin, HQ)<i>, Lonicerae Japonicae Flos</i> (jinyinhua, JYH)<i>, Salviae Miltiorrhizae Radix et Rhizoma</i> (danshen, DS)<i>, and Paeoniae Radix Rubra</i> (chishao, CS). These herbs collectively exhibit cold, warm, and neutral properties; bitter, sweet, and pungent tastes; and tropism to the liver, lung, and stomach meridians, reflecting a therapeutic strategy that clears heat, resolves dampness, and promotes blood circulation. The core triad <i>Eriobotryae Folium</i> (pipaye, PPY), <i>Mori Cortex</i> (sangbaipi, SBP), and <i>Scutellariae Radix</i> and formulas like Erzhi Pills, Sanhuang Lotion, and Xiaoyao Powder suggest key clinical combinations. Network pharmacology revealed that several biological pathways may play important roles in acne treatment, including pathways in cancer, lipid and atherosclerosis, fluid shear stress and atherosclerosis, and chemical carcinogenesis-receptor activation. These pathways are closely linked to inflammation, sebum metabolism, and oxidative stress-core pathological processes in acne vulgaris. Finally, docking showed quercetin, kaempferol, luteolin, and wogonin had strong affinities with AKT1, TNF, IL-6, and TP53 (energies < -5.0 kcal/mol). These findings provide a pharmacological basis for the clinical efficacy of the identified herbs and offer directions for further experimental validation. Crucially, atomistic molecular dynamics simulations and free energy landscape analysis validated the dynamic and thermodynamic stability of these four lowest-energy complexes, confirming that these flavonoids lock the target proteins into deeply stabilized, inactive conformations. Overall, this study bridges clinical experience with dynamic structural biology, providing a high-resolution molecular rationale for anti-acne therapeutics.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 2","pages":"205"},"PeriodicalIF":0.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655468","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 docking and molecular dynamics simulation analysis of phytochemicals targeting human metapneumovirus fusion protein.","authors":"Amna Syeda, Rafat Ali, Md Amjad Beg","doi":"10.1007/s40203-026-00716-2","DOIUrl":"10.1007/s40203-026-00716-2","url":null,"abstract":"<p><p>Human Metapneumovirus (HMPV) continues to be a major cause of respiratory infections around the world, despite the availability of many treatment options and the existence of effective vaccines against other respiratory viruses such as influenza and parainfluenza virus. Since the virus poses a significant public health threat, yet there are no approved antiviral medications or vaccines against it, an effective therapy is still needed. This work aimed to find natural phytochemical inhibitors for HMPV fusion (F) glycoprotein by using a structure-based in silico drug discovery approach. As the protein has an important role in viral attachment to cells and membrane fusion, the choice of HMPV F glycoprotein as a drug target seemed to be appropriate. Compounds from the Indian Medicinal Plants, Phytochemistry and Therapeutics (IMPPAT) 2.0 database were screened by performing molecular docking analysis of their interactions and binding affinities towards the HMPV F protein. The top-ranking molecules were further analyzed by conducting 300-nanosecond molecular dynamics simulations in order to obtain insights into complex stabilities, flexibilities, and conformations. Several phytochemicals showed promising docking results and contributed to structural stabilization of the target protein, especially its heptad repeat and fusion loops regions responsible for membrane fusion. These findings support their potential as fusion inhibitors and offer a promising foundation for future experimental validation and antiviral drug development.</p><p><strong>Graphical abstract: </strong>Human Metapneumovirus (HMPV) causes serious respiratory illness, yet no vaccines or antivirals exist. Using computer-based screening, we tested natural compounds from the IMPPAT 2.0 database against the virus's fusion (F) protein. Several phytochemicals showed stable binding, especially at key functional regions, suggesting they could block viral entry. These results highlight promising natural candidates for future HMPV drug development.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-026-00716-2.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 2","pages":"206"},"PeriodicalIF":0.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655503","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}