Journal of Biomolecular Structure & Dynamics最新文献

{"title":"Exploring a kinase inhibitor targeting PI3KCA mutant cancer cells.","authors":"Dana F AlKharboush, Maan T Khayat, Alam Jamal, Moustafa E El-Araby, Aeshah A Awaji, Mohammad Imran Khan, Abdelsattar M Omar","doi":"10.1080/07391102.2025.2502137","DOIUrl":"https://doi.org/10.1080/07391102.2025.2502137","url":null,"abstract":"<p><p>The PI3K/mTOR signaling pathway is often disrupted in human cancers, with PI3Kα being one of the most mutated kinases. There has been considerable interest in developing small-molecule inhibitors aimed at blocking the mutant PI3Kα-driven phosphatidylinositol 3-kinase (PI3K) signaling pathway as a potential treatment for cancer. In this study, we describe our effort to identify a compound, phenylacetamide-1H-imidazol-5-one (KIM-161), from our in-house oncogenic kinase-targeting inhibitors. KIM-161 showed excellent anti-proliferative activities at sub-nanomolar concentrations, primarily against mutant PI3Kα breast cancer cell lines, when compared with wild-type PI3Kα breast cancer cell lines, producing both dose- and time-dependent effects with an IC50 range of 1.42 - 0.064 µM. Next, we observed that KIM-161 was able to induce ROS production by modulating breast cancer metabolism, suggesting its broad effects on mutant PI3Kα regulated downstream pathways. We also computationally analyzed the binding interactions between KIM-161 and PI3K-alpha (PDB ID: 8EXL). Molecular docking showed that KIM-161 had a docking score of -7.44 Kcal/mol, compared to the reference compound, which had a docking score of -7.67 Kcal/mol. Moreover, molecular dynamics simulation studies demonstrated that the PI3Ka-KIM-161 complex remained stable throughout the 100 ns simulation, when compared to the PI3Ka complex with the co-crystallized inhibitor. These findings present KIM-161 as a promising lead, providing valuable insights into treatment approaches and resistance mechanisms associated with PI3K inhibitors in specific PIK3CA-mutant cancer subtypes.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-18"},"PeriodicalIF":2.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 identification of potential 2-thioxothiazolidin-4-one derivatives against peroxisome proliferator-activated receptor-gamma by molecular docking, MM-GBSA, molecular dynamic simulation, and toxicity studies.","authors":"Mahendra Gowdru Srinivasa, Manohar M, Sudeep D Ghate, Shivakiran Alva, Vinay C Sangamesh, Revanasiddappa B C","doi":"10.1080/07391102.2025.2506713","DOIUrl":"https://doi.org/10.1080/07391102.2025.2506713","url":null,"abstract":"<p><p>The metabolic disorder diabetes mellitus occurs when there is an inadequate level of insulin or excessive insulin resistance. There has been evidence that this pathogenesis has been approached <i>via</i> a different strategy. It activates homeostatic glucose and improves peripheral glucose utilization by targeting the PPAR-γ. In this regard, the present study aims to investigate 2-thioxothiazolidin-4-one derivatives <b>(D1-15)</b> as PPAR-γ regulators by computational approach followed by evaluation of physicochemical properties and ADMET profiles. The protein target PPAR-γ (PDB ID: 3DZY) was docked against 2-thioxothiazolidin-4-one derivatives using the glide suite. The results indicate the high binding affinity of compounds <b>D7, D11</b> (-6.509 and -7.276 kcal/mol) and they were compared against standard drug rosiglitazone <b>(-7.289</b> kcal/mol). MD simulation studies were also carried out at 150 ns to identify the key interactions in protein-ligand complexes in a dynamic environment not only to confirm our findings but to validate them as well. The findings indicated that certain designed compounds, namely D7 and D11, exhibited notable activity against PPAR-γ inhibitors, as evidenced by their favorable glide scores. The chosen derivatives of 2-thioxothiazolidin-4-one appear to hold promise as potential sources for advancing the development of antidiabetic agents targeting the PPAR-γ enzyme.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-13"},"PeriodicalIF":2.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening the absorbed active components of Danggui Sini Decoction in the treatment of diabetic peripheral neuropathy by network pharmacology combined with molecular docking and dynamics simulation.","authors":"Qichang Xing, Wei Li, Jia Chen, Zheng Liu, Yixiang Hu, Wencan Li, Xiang Liu, Can Xiao","doi":"10.1080/07391102.2025.2505251","DOIUrl":"https://doi.org/10.1080/07391102.2025.2505251","url":null,"abstract":"<p><p>Diabetic peripheral neuropathy (DPN) is a prevalent and detrimental condition that can be debilitating and even fatal if not treated; however, there remains a dearth of efficacious pharmaceutical interventions for DPN. The Danggui Sini Decoction (DSD), a renowned traditional Chinese medicine prescription, has been utilized in the clinic for the treatment of DPN because of its efficacy in addressing yang deficiency and cold coagulation. However, the active components and underlying mechanisms of DSD remain unclear. In this study, we devised a conventional approach to screen the absorbed active ingredients in DSD, employing LC-MS to identify the principal active compounds of DSD in the blood of rats and then validating these components using network pharmacology for target prediction and molecular dynamics simulations for further validation. We identified 17 potentially active components in the serum and 47 main targets that might be relevant for treating DPN with DSD. These targets were associated with pathways including neuroactive ligand-receptor interaction, HIF-1, and AGE-RAGE signaling pathways, all of which are implicated in diabetic complications. Through molecular docking, we found that glycyrrhetinic acid and betulonic acid-two active components identified by LC-MS in the DSD-containing serum of rats-exhibited strong binding activities with AKT1 and STAT3. Furthermore, molecular dynamics simulations of the docking results indicated that the AKT1-glycyrrhetinic acid and AKT1-betulonic acid complexes were highly stable throughout the kinetic simulations. These findings suggest that the molecular mechanism underlying DSD treatment of DPN may involve the activation of AKT1 by glycyrrhetinic acid and betulonic acid.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-14"},"PeriodicalIF":2.7,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of potential 3CLpro inhibitors-modulators for human norovirus infections through an advanced virtual screening approach.","authors":"Shovonlal Bhowmick, Tapan Kumar Mistri, Mohammad K Okla, Ibrahim A Saleh, Achintya Saha, Pritee Chunarkar Patil","doi":"10.1080/07391102.2025.2502672","DOIUrl":"https://doi.org/10.1080/07391102.2025.2502672","url":null,"abstract":"<p><p>The present study aimed to screen small molecular compounds such as human noroviruses (HuNoV) inhibitors/modulators that could potentially be responsible for exhibiting some magnitude of inhibitory/modulatory activity against HuNoV 3CLPro. The structural similarity-based screening against the ChEMBL database is performed against known chemical entities that are presently under pre-clinical trial. After the similarity search, remaining molecules were considered for molecular docking using SCORCH and PLANTS. On detailed analyses and comparisons with the control molecule, three hits (CHEMBL393820, CHEMBL2028556, and CHEMBL3747799) were found to have the potential for HuNoV 3CLpro inhibition/modulation. The binding interaction analysis revealed several critical amino acids responsible to hold the molecules tightly at the close proximity site of the catalytic residues of HuNoV 3CLpro. Further, MD simulation study was performed in triplicate to understand the binding stability and potentiality of the proposed molecule toward HuNov 3CLpro. The binding free energy based on MM-GBSA has revealed their strong interaction affinity with 3CLpro.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-17"},"PeriodicalIF":2.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational insights into mutation-induced binding changes in Bruton's Tyrosine Kinase with non-covalent inhibitors.","authors":"Justice Josiah Mallen, Shilpa Sharma, Md Nazmul Hasan, Arjun Saha","doi":"10.1080/07391102.2025.2502140","DOIUrl":"https://doi.org/10.1080/07391102.2025.2502140","url":null,"abstract":"<p><p>Kinases are pivotal in regulating signaling pathways, and their dysregulation is associated with various diseases, including cancers, making them prime therapeutic targets. Bruton's Tyrosine Kinase (BTK) is crucial for B-cell development, and BTK inhibitors have proven effective in treating B-cell malignancies like Chronic Lymphocytic Leukemia (CLL). Non-covalent inhibitors offer a promising therapeutic approach by avoiding covalent bond formation with the protein. However, therapeutic resistance due to BTK mutations in the catalytic domain has led to relapses and refractory cases in CLL, highlighting the need for a deeper understanding of these mutations' impact on treatment outcomes. This study investigates the effects of four prevalent single-point mutations-A428D, T474I, C481S, and L528W-within the catalytic domain of BTK. Using 12.5 microseconds of molecular dynamics simulations and computational drug discovery methods, we examine how these mutations influence the binding affinities and interactions of non-covalent BTK inhibitors. Molecular Mechanics-Poisson-Boltzmann Surface Area (MM-PBSA) analysis showed that mutant forms of BTK significantly decreased ligand binding free energies compared to the wild types, with a few exceptions. With pocket volume and solvent-accessible surface area analysis, we also show that mutations reduce the binding pocket volume, forcing the inhibitors to move out of the pocket, disrupting the critical non-covalent interactions of the inhibitors with mutant BTK. This confirms the experimental and clinical observations of why these BTK mutations impair inhibitor efficacy fostering drug resistance. Our results offer vital insights for designing next-generation BTK inhibitors to overcome resistance and enhance therapeutic outcomes in B-cell malignancies.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-17"},"PeriodicalIF":2.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic and molecular insights into a <i>cypovirus</i> isolated from <i>Antheraea assamensis</i> Helfer (<i>Lepidoptera: Saturniidae</i>) and modelling of its polyhedrin protein structure.","authors":"Surajit Basak, Kangkon Saikia, Aditya Narayan Konwar, Rahul P Hepat, Aparup Patra, Rajiv Borah, Jamie Bojko, Ashis Kumar Mukherjee, Debajit Thakur","doi":"10.1080/07391102.2025.2501674","DOIUrl":"https://doi.org/10.1080/07391102.2025.2501674","url":null,"abstract":"<p><p><i>Antheraea assamensis</i> Helfer (<i>A. assamensis</i>) or Muga silkworm is popularly known for producing golden silk and endemic to the region of Northeast India. The present work characterizes a <i>cypovirus</i> variant infecting <i>A. assamensis</i> larvae, exhibiting characteristic symptoms of flacherie disease. Scanning electron microscope and transmission electron microscope imaging revealed the presence of polyhedral occlusion bodies (OBs) and virion particles measuring 40-50 nm in size. The cypovirus strain comprised of 10 dsRNA genome segments, which were sequenced, assembled and annotated. The encoded viral proteins from different genomic fragments were studied. The phylogenetic analysis of the RNA-dependent RNA polymerase and polyhedrin revealed a close relationship with the previously classified Antheraea mylitta cypovirus 4. The strain was characterized as Antheraea assamensis cypovirus 4 (AaCPV4) with substantial genomic and proteomic evidence that was previously unexplored. The peptide fingerprints of the polyhedrin protein were analysed in the diseased and healthy silkworm lysate by using LC-MS/MS. The polyhedrin protein of AaCPV4 was modelled by different <i>in silico</i> methods and compared with the previously reported cypovirus strains. The multimeric models of polyhedrin were studied and demonstrated the mechanism of formation of OB geometry. Our study provides new insights into the complete genome of AaCPV4 and its viral proteins, which were previously unknown. The present work will help in understanding the differentiation of CPV4 variants infecting <i>Antheraea</i> species and different host adaptations.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-15"},"PeriodicalIF":2.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and synthesis of new benzimidazole-hybrids as anti-microbial agents: exploring the mechanistic insights as DNA gyrase inhibitors via <i>in silico</i> and <i>in vitro</i> based studies.","authors":"Anand Maurya, Upendra Kumar Patel, Punit Tiwari, Gaurav Joshi, Roshan Kumar, Ragini Tilak, Alka Agarwal","doi":"10.1080/07391102.2025.2501669","DOIUrl":"https://doi.org/10.1080/07391102.2025.2501669","url":null,"abstract":"<p><p>Two series of antibacterial agents, 1,2,3-triazole and aminopyrimidine benzimidazole hybrids, were designed, synthesized, and characterized by IR, NMR, Mass spectroscopy, and X-ray crystallography studies. The biological studies revealed that compounds <b>5a</b>, <b>5b</b>, <b>5c</b>, <b>5d</b>, <b>5e</b>, <b>5f</b>, <b>5g</b>, <b>5h</b>, <b>8d</b>, <b>8e</b>, <b>9d</b>, <b>9e</b>, <b>9f</b>, <b>9h</b>, <b>9j</b>, and <b>9k</b> exhibited significant antibacterial activity <i>in vitro</i> compared to the standard drug ciprofloxacin, against Gram-positive and Gram-negative bacterial strains. The study of hemotoxicity displayed a negligible toxicity profile for all the compounds. Furthermore, the mechanistic insights predicted <i>via</i> molecular docking studies on DNA gyrase revealed (Glide Scores) that compounds <b>5c</b> and <b>5f</b> possess better affinity within the active domain of DNA gyrase, which was further corroborated using molecular dynamics followed by direct DNA gyrase-based inhibition assays. Compound <b>5f</b> was the most potent, while <b>5c</b> showed an equipotent inhibition compared to a standard drug.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-20"},"PeriodicalIF":2.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioassay-guided isolation of a new cytotoxic compound targeting carbonic anhydrase-II: <i>in-vitro</i> structure-activity relationships and dynamics studies.","authors":"Rabia Maqsood, Saeed Ullah, Faizullah Khan, Muhammad Waqas, Sobia Ahsan Halim, Ajmal Khan, Javid Hussain, Usama Qayum, Simon Gibbons, Najeeb Ur Rehman, Amjad Hussain, Ahmed Al-Harrasi","doi":"10.1080/07391102.2025.2500680","DOIUrl":"https://doi.org/10.1080/07391102.2025.2500680","url":null,"abstract":"<p><p>Bioassay-guided isolation of <i>Anogeissus dhofarica</i> A.J. Scott afforded one new natural product (lupeol butyl ether, <b>1</b>), along with sixteen known metabolites (<b>2</b>-<b>17</b>) reported from this source for the first time. Structural elucidation of the isolates was performed by NMR and mass spectrometry. An <i>in vitro</i> carbonic anhydrase-II (CA-II) inhibition assay was performed on the crude extract, the fractions, and the resulting pure constituents. The activity against CA-II of the crude extract and fractions was in the range of IC₅₀ 45.10-102.56 µg/mL. Among the isolates, <b>14</b> was the most active with an IC₅₀ of 7.19 ± 0.20 µM followed by <b>10</b> (IC₅₀ = 13.61 ± 0.30 µM), <b>12</b> (IC₅₀ = 17.30 ± 0.58 µM) and <b>1</b> (21.63 ± 0.48 µM), with the remaining compounds having moderate to low inhibition. Fourteen compounds were evaluated against breast cancer (MDA-MB-231) and normal cell (3T3-L1) lines in an MTT assay, with most natural products exhibiting moderate activity against MDA-MB-231 cells (<b>1</b>, IC₅₀ = 34.5 ± 0.8 μM/mL), and less active to the normal cell line. Additionally, the molecular binding of the active hits was predicted through an in-silico approach, specifically docking molecular dynamic (MD) simulations, which revealed that acetate and carboxyl moieties play an important role in ligand binding with the Zn²⁺ ion of the CA-II active site. The MD simulation of the structure dynamics revealed that the most active inhibitors (<b>10</b> and <b>14</b>) had strong affinity with the CA-II active site and brought structural conformational changes to the protein.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-17"},"PeriodicalIF":2.7,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of the bonding affinities between human PSGL-1 and Vpu derived from the different HIV-1 groups - in silico insights.","authors":"Silvere D Zaongo, Farooq Rashid, Muhammad Suleman, Vijay Harypursat, Fangzhou Song, Yaokai Chen","doi":"10.1080/07391102.2025.2500682","DOIUrl":"https://doi.org/10.1080/07391102.2025.2500682","url":null,"abstract":"<p><p>Human P-selectin glycoprotein ligand 1 (PSGL-1) and HIV-1 viral protein U (Vpu) play major roles in limiting and increasing the ability of HIV-1 to infect cells, respectively. There is currently no published data reporting on the specific interactions between PSGL-1 and Vpu, and possible outcomes and consequences of these interactions. To date, it has only been established that Vpu binds human PSGL-1 to degrade PSGL-1 and therefore promote HIV replication. There are, however, four different types of HIV-1, and it would be helpful to know how VpuM, VpuN, VpuO, and VpuP can bind to and possibly inhibit PSGL-1 expression. Bioinformatics methods were used to find out how strongly each type of Vpu found in the different HIV-1 groups bonds with human PSGL-1. Thus, we used molecular docking (MD) and molecular dynamics simulations (MDS) to figure out how PSGL-1 and VpuM, VpuN, VpuO, and VpuP interact with each other. To ensure the reliability of the predicted outcomes, the binding energy of each model was calculated using the MM/GBSA technique. Our findings show that PSGL-1-VpuP (4 H bonds, 2 salt bridges) and PSGL-1-VpuM (3 H bonds, 2 salt bridges) have stronger bonding affinities than PSGL-1-VpuN (4 H bonds, no salt bridges) and PSGL-1-VpuO (2 H bonds, 1 salt bridge). The MDS test also shows that PSGL-1-VpuM and PSGL-1-VpuP protein complexes are more stable and compact, with lower residual fluctuations compared to PSGL-1-VpuN and PSGL-1-VpuO protein complexes. Binding free energies of -82.27 ± 1.35 kcal/mol, -82.17 ± 0.84 kcal/mol, -67.84 ± 0.63 kcal/mol, and -131.86 ± 1.08 kcal/mol were recorded for each of PSGL1-VpuM, PSGL1-VpuN, PSGL1-VpuO, and PSGL1-VpuP, respectively, which further supports our results. Our research shows that Vpu from the M and P HIV-1 groups may be better at blocking human PSGL-1 than VpuO and VpuN groups. These results are novel in this specific realm of HIV research, and as such, further investigations in more robust experimental studies are warranted.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-11"},"PeriodicalIF":2.7,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatics approach reveals the modulatory role of JUN in atorvastatin-mediated anti-breast cancer effects.","authors":"Mohamed Y Foda, Sara A Al-Shun, Guendouzi Abdelkrim, Mohamed L Salem, Nevin A Salah, Omali Y El-Khawaga","doi":"10.1080/07391102.2025.2499950","DOIUrl":"https://doi.org/10.1080/07391102.2025.2499950","url":null,"abstract":"<p><p>Atorvastatin, a widely prescribed cholesterol-lowering drug, has recently shown potential anticancer effects. However, its influence on gene expression and its biological functions in cancer, in particular breast cancer, still unclear. We aim to identify the dysregulated genes associated with atorvastatin treatment and the main players in their biological network. A total of 103 differentially expressed genes (DEGs) in the unified signature were identified, and the functional enrichment analysis suggested their relation to multiple cancer-related pathways. JUN was identified as the hub gene in the protein-protein interaction (PPI) network and was shown to be responsive to atorvastatin in breast cancer. Atorvastatin exhibited notable predicted cytotoxicity against breast cancer lines, with the activity positively correlated with JUN expression. JUN was significantly downregulated in breast cancer expression inversely correlated with cancer progression, whereas higher JUN expression was linked with better survival outcomes. Atorvastatin may directly interact with JUN protein forming a more compact and stable conformation. These findings demystify the potential therapeutic mechanism of atorvastatin in breast cancer, possibly by fine tuning of JUN expression. As such, JUN might serve as a valuable prognostic biomarker in breast cancer.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-21"},"PeriodicalIF":2.7,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}