Journal of Biomolecular Structure & Dynamics最新文献

{"title":"<i>In silico</i> analysis of bioactive compounds of Nigella sativa as potential inhibitors of NS5B RdRp protein involved in the pathogenesis of hepatitis C virus.","authors":"Tarique Sarwar, Ahmad Almatroudi, Saleh A Almatroodi, Hajed Obaid A Alharbi, Arshad Husain Rahmani","doi":"10.1080/07391102.2025.2515254","DOIUrl":"https://doi.org/10.1080/07391102.2025.2515254","url":null,"abstract":"<p><p>The Hepatitis C virus (HCV) is a small, enveloped virus characterized by a positive-sense single-stranded RNA belonging to the Flaviviridae family. It causes hepatitis C, which leads to liver inflammation. It manifests as both acute and chronic hepatitis, ranging from mild illness to life-threatening conditions, such as liver fibrosis, cirrhosis, and hepatocellular carcinoma. The NS5B RNA-dependent RNA polymerase (RdRp) protein plays a vital role in the replication of the hepatitis C virus as the main RNA-synthesizing enzyme. It is crucial for forming new viral RNA, making it an ideal target for antiviral drugs. Inhibiting NS5B can inhibit virus replication, potentially preventing severe liver diseases, including cancer. Scientists have mapped the structure of the NS5B RdRp, revealing how different inhibitors interact with it, guiding the creation of targeted drugs. Nigella sativa, known for diverse bioactive compounds, is now being explored for its potential to combat viruses. Our research aims to determine whether compounds extracted from Nigella sativa can inhibit the NS5B RdRp enzyme of HCV. Through advanced computational analysis and molecular docking, Nigella sativa's phytoconstituents were scrutinized for their ability to bind and potentially inhibit NS5B RdRp. Amentoflavone, Rutin, and Catechin were selected based on their pharmacokinetic and enzyme-binding properties, which prompted further examination. Thorough molecular dynamics simulations affirmed the formation of stable complexes between these molecules and NS5B RdRp and provided valuable information about their influence on the enzyme's structural stability. The findings suggest these compounds have potent inhibitory actions, highlighting them as potential natural medicinal options against hepatitis C.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-20"},"PeriodicalIF":2.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248037","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":"Investigation of the interaction between bromocriptine and human serum albumin with spectroscopic techniques and computational approaches.","authors":"Sevinc Ayla Ozsar, Cigdem Kanbes-Dindar, Fazal Rehman, Saharuddin B Mohamad, Bengi Uslu","doi":"10.1080/07391102.2025.2513017","DOIUrl":"https://doi.org/10.1080/07391102.2025.2513017","url":null,"abstract":"<p><p>Fluorescence and absorption spectroscopy coupled with molecular docking techniques were chosen to reveal the molecular relationship between bromocriptine (BRC), a dopamine agonist, and human serum albumin (HSA), the major carrier protein in the bloodstream. The gradual decrease of Stern-Volmer constant (K_SV) with increasing temperatures noted that BRC induced quenching in HSA fluorescence occurred <i>via</i> a static quenching mechanism, thus indicating the formation of complexes between BRC and HSA. The changes observed in the UV-vis absorption spectra of HSA as a result of BRC addition and the fact that the biomolecular quenching rate constants (K_q) calculated for the BRC-HSA interaction are significantly larger than the highest value of the dynamic quenching rate constant also support this conclusion. Considering the experimentally obtained binding constant (K_a) values ​​(2.6 - 3.8 x 10⁴ M^-1), BRC appeared to bind to HSA with a moderate affinity. Analysis of thermodynamic data suggested the association of hydrophobic interactions, H-bonds and van der Waals forces as the main interaction forces in the BRC-HSA binding. It was determined by 3-D fluorescence spectra that the binding of BRC to the protein led to significant changes in the Tyr/Trp microenvironment of the protein. Docking analyses and drug displacement experiments identified that BRC likely binds to subdomain IIA (Site I) of HSA.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-18"},"PeriodicalIF":2.7,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225570","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":"Exploring the anti-inflammatory potential of purified <i>Plumbago zeylanica</i> L. root extracts: an integrated <i>in silico</i>, <i>in vitro</i>, and <i>in vivo</i> approach.","authors":"Nandita Mandal, Mousumi Paul, Yadu Nandan Dey, Parthasarathi Panda, Pukar Khanal, Manish M Wanjari, Tamal Pal, Tanmoy Das, Kunal Bhattacharya, Shridhar Chougule","doi":"10.1080/07391102.2025.2513015","DOIUrl":"https://doi.org/10.1080/07391102.2025.2513015","url":null,"abstract":"<p><p>The utilization of purified roots from <i>Plumbago zeylanica</i> in traditional Ayurvedic medicine for addressing various inflammatory conditions such as arthritis prompted this study to explore the <i>in vitro</i> anti-inflammatory potential of distinct extracts derived from these roots. Additionally, the study assessed the anti-inflammatory and analgesic activities of the most potent extract in Wistar rats (either sex) and predicted the bioactive phytoconstituents through in silico molecular docking with the cyclooxygenase-II enzyme. The purification of the plant material involved the traditional detoxification process of shodhana. The purified roots underwent hot continuous extraction (Soxhlet extraction) to produce extracts with increasing polarity. The <i>in vitro</i> anti-inflammatory activity of these extracts, at varying concentrations, was evaluated through assays measuring the inhibition of albumin denaturation and hypotonicity-induced hemolysis. Analgesic activity and anti-inflammatory activities were assessed in rats through formalin-induced pain and carrageenan-induced paw edema models, respectively. Prediction of bioactive compounds was conducted through molecular docking and dynamics of different phytoconstituents of the purified roots of <i>P. zeylanica</i> with the cyclooxygenase-II (COX-2) enzyme. <i>In vitro</i> studies demonstrated the anti-inflammatory effects in different extracts, methanolic extract being the most potent. <i>In vivo</i> studies revealed analgesic and anti-inflammatory activities in the methanolic extract. Molecular docking results indicated good interaction between phytoconstituents of the methanolic extract and COX-2 enzyme, with chitranone being the most inhibiting compound having stable ligand anchoring. The study concludes that the methanolic extract of purified roots of <i>P. zeylanica</i> possesses notable anti-inflammatory and analgesic activities, potentially attributed to the presence of its COX-2 inhibitor compounds.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-23"},"PeriodicalIF":2.7,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234273","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":"Bioprospecting potential, metabolic profiling, and molecular docking studies of metabolites from endophytic fungi associated with <i>Teucrium stocksianum</i>.","authors":"Sajid Iqbal, Faisal Ahmad, Abdul Haleem, Bushra Rehman, Salma Mohammed Aljahdali, Sajjad Ahmad, Muniba Jadoon, Qurban Ali, Talmeez Ur Rehman, Sajjad Ahmed Khan, Safia Ahmed","doi":"10.1080/07391102.2025.2513571","DOIUrl":"https://doi.org/10.1080/07391102.2025.2513571","url":null,"abstract":"<p><p>Endophytic fungi associated with <i>Tecurium stocksianum</i> signify under-explored repository of promising biologically active metabolites. The aim of this current research was to identify endophytic fungi with antimicrobial properties that are linked to <i>T. stocksianum</i>. Natural compounds found in plants have demonstrated significant potential, but often, the levels of these bioactive substances in plant tissues are insufficient. To tackle this challenge, the study sought to uncover and utilize endophytes. Following cultivation, crude ethyl acetate extracts of the endophytes were screened for antimicrobial, antioxidant, cytotoxic activities and subjected to high resolution LCMS characterization. Among nine of the isolated endophytic fungi, two isolates HS11 and HS12 expressed significant biological activities. Metabolic profiling of the partially purified ethyl acetate extract of the isolate HS12 <i>Fusarium oxysporium</i> led to the detection of potent bioactive molecules, i.e. (5ξ)-11,12-Dihydroxyabieta-8(14),9(11),12-trien-20-oic acid, 2,2'-Methylenebis(4-methyl-6-tert-butyl phenol, L-Phenylalanine and 7-Methoxycoumarin-4-acetic acid. These metabolites have been investigated <i>via</i> molecular docking strategy against a conserved antibiotic resistance protein target of ESKAPE pathogens. Molecular dynamics simulation has further validated these complexes and has been inferred that 2 complex systems are more stable than the (5ξ)-11,12-Dihydroxyabieta-8(14),9(11),12-trien-20-oic acid complex system in a 100 ns time scale. Results inferred high binding affinities of the compounds against the target molecule. Thus, our study demonstrates promising bio-prospecting potential of endophytic fungi associated with <i>T. stocksianum</i> and advocates up-scaling for compound isolation studies; in particular; from candidate HS12 <i>F. oxysporium.</i></p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-16"},"PeriodicalIF":2.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215950","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":"New derivatives of paracetamol as potent <i>α</i>-glucosidase inhibitors: synthesis, <i>in vitro,</i> and <i>in silico</i> studies.","authors":"Rukhsana Bibi, Mumtaz Ali, Abdul Latif, Saeed Ullah, Aftab Alam, Ammara, Manzoor Ahmad, Asaad Khalid, Ajmal Khan, Ahmed Al-Harrasi","doi":"10.1080/07391102.2025.2502136","DOIUrl":"https://doi.org/10.1080/07391102.2025.2502136","url":null,"abstract":"<p><p>Twenty novel derivatives (<b>4</b>-<b>24</b>) of the commercially available drug paracetamol (<b>1</b>) were synthesized in decent yields by refluxing ethyl chloroacetate with paracetamol in the presence of potassium carbonate in DMF solvent to obtain ethyl 2-(4-acetamidophenoxy)acetate (<b>2</b>), which was further treated with hydrazine hydrate in absolute ethanol to get paracetamol hydrazide (<b>3</b>). Finally, various substituted aliphatic and aromatic aldehydes were refluxed with the hydrazide to get hydrazone-Schiff base derivatives (<b>4-24</b>). Structures of the synthesized derivatives were deduced through modern spectroscopic techniques (¹³C-,¹H-NMR, and HR-ESI-MS). All the compounds were tested for <i>α</i>-glucosidase inhibitory potential because <i>α</i>-glucosidase inhibitors slow down carbohydrate digestion thus normalize blood glucose level indicates a promising target for the treatment of diabetes. Among them, five compounds including <b>4</b> (IC₅₀ = 90.98 ± 0.68 µM), <b>5</b> (IC₅₀ = 78.12 ± 0.47 µM), <b>11</b> (IC₅₀ = 27.54 ± 0.16 µM), <b>12</b> (IC₅₀ = 83.52 ± 0.70 µM), and <b>13</b> (IC₅₀ = 89.38 ± 0.67 µM) were found potent inhibitors of <i>α</i>-glucosidase as compared to the standard acarbose (IC₅₀ = 873.34 ± 1.67 µM). <i>In silico</i> studies were conducted to evaluate the binding affinity of the synthesized compounds with the target enzyme.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-14"},"PeriodicalIF":2.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215951","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":"Stimulation of the immune system and apoptosis induction by new cobalt(III) H₂salophen complexes in breast cancer mouse model and docking calculations.","authors":"Fatemeh Ghorbani, Rana Ezzeddini, Dariush Haghmorad, Bahman Yousefi, Ali Khaleghian, Majid Ghorbani, Mehdi Salehi, Rahime Eshaghi Malekshah, Mahdieh Tarahomi, Amir Salek Farrokhi","doi":"10.1080/07391102.2025.2511149","DOIUrl":"https://doi.org/10.1080/07391102.2025.2511149","url":null,"abstract":"<p><p>The increasing resistance of cancer drugs, especially in the treatment of breast cancer, underlines the urgent need for new and effective cancer drugs. Chemotherapeutic agents based on metal complexes are recognized as highly effective treatment options. The aim of this study is to synthesize a non-platinum chemotherapeutic agent with high efficacy and to investigate its therapeutic effect in mice with tumors. Novel transition metal complexes derived from Schiff base ligands (cobalt(III) H₂salophen complexes) were synthesized, characterized and optimized by quantum calculations based on DFT-D. MDA-MB231 and 4T1 cells were cultured and the scavenging and hemolysis activity, cytotoxic effect, migration and apoptosis were investigated. In addition, the therapeutic effects of the complex were investigated in mice with tumors. The interactions of the target macromolecules were investigated by molecular docking. The results showed that the complexes exhibited considerable cytotoxicity, apoptosis and migration inhibition against tumor cell lines and inhibition of tumor growth in mice, and greatly increased IFN-γ and TNF-α and reduced IL-4 and IL-1β. Data suggest that complex C treatment can enhance immune responses with a Th1 dominance by inducing the secretion of proinflammatory cytokines. Molecular docking experiments confirmed that complex C binds to the most stable state and induces apoptosis by interacting with the DNA minor groove. Our results suggest that complex C triggers apoptosis, leading to a lethal effect on malignant tumor cells, and has the potential to inhibit tumor growth through direct cytotoxic effects. It also stimulates the immune system and alters the cytokine profile.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-22"},"PeriodicalIF":2.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199244","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":"Repurposing integrase inhibitors against human T-lymphotropic virus type-1: a computational approach.","authors":"Prashasti Sinha, Anil Kumar Yadav","doi":"10.1080/07391102.2024.2304681","DOIUrl":"10.1080/07391102.2024.2304681","url":null,"abstract":"<p><p>Adult T-cell Lymphoma (ATL) is caused by the delta retrovirus family member known as Human T-cell Leukaemia Type I (HTLV-1). Due to the unavailability of any cure, the study gained motivation to identify some repurposed drugs against the virus. A quick and accurate method of screening licensed medications for finding a treatment for HTLV-1 is by cheminformatics drug repurposing in order to analyze a dataset of FDA approved integrase antivirals against HTLV-1 infection. To determine how the antiviral medications interacted with the important residues in the HTLV-1 integrase active regions, molecular docking modeling was used. The steady behavior of the ligands inside the active region was then confirmed by molecular dynamics for the probable receptor-drug complexes. Cabotegravir, Raltegravir and Elvitegravir had the best docking scores with the target, indicating that they can tightly bind to the HTLV-1 integrase. Moreover, MD simulation revealed that the Cabotegravir-HTLV-1, Raltegravir-HTLV-1 and Elvitegravir-HTLV-1 interactions were stable. It is obvious that more testing of these medicines in both clinical trials and experimental tests is necessary to demonstrate their efficacy against HTLV-1 infection.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4686-4697"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485635","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":"Development of venetoclax with 2-hydroxypropyl-beta-cyclodextrin inclusion complex for improved bioavailability.","authors":"Smalant Kishor Patil, Padakanti Sandeep Chary, Sarvan Maddipatla, Y V Madhavi, Siva Singothu, Vasundhra Bhandari, Ekta Pardhi, Kuldeep Kumar Bansal, Neelesh Kumar Mehra","doi":"10.1080/07391102.2024.2305695","DOIUrl":"10.1080/07391102.2024.2305695","url":null,"abstract":"<p><p>Cyclodextrin complexes loaded with venetoclax for improved solubility and therapeutic efficacy as repurposed drug. The venetoclax-cyclodextrin inclusion complex was prepared using kneading method. Primarily in-silico molecular docking study was performed to examine the possible interaction between venetoclax and hydroxypropyl-β-cyclodextrin (HP-β-CD) and extensively characterized. The in-vitro studies were performed using A-549 lung epithelial cancer cells. The in-vivo pharmaco-kinetic studies was performed on wistar rats. The aqueous solubility of venetoclax was increased upto 3.16 folds, as compared with pure venetoclax with entrapment efficiency (EE%) was determined 95.44 ± 0.3%. In-vitro cytotoxicity studies were carried on A-549 lung epithelial cancer cells, wherein BCL-2 receptors were highly over-expressed and IC 50 values for venetoclax and venetoclax- HP-β-CD complex was calculated at 24 and 48 hrs in the order of 1.241 µg/ml, 0.68 µg/ml and 0.757719 µg/ml, 0.6125 µg/mL, respectively. The oral bioavailability was increased 4.03 times compared to the pure drug. The venetoclax-HP-β-CD inclusion complexes showed the increased aqueous solubility with improved anticancer activities.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4847-4864"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511923","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":"Quantum biochemical analysis of the binding interactions between a potential inhibitory drug and the Ebola viral glycoprotein.","authors":"Jaerdyson M da Rocha, Daniel M de O Campos, Stephany C Esmaile, Gabriela de L Menezes, Katyanna S Bezerra, Roosevelt A da Silva, Edilson D da S Junior, Jehad Zuhair Tayyeb, Shopnil Akash, Umberto L Fulco, Taha Alqahtani, Jonas I N Oliveira","doi":"10.1080/07391102.2024.2305314","DOIUrl":"10.1080/07391102.2024.2305314","url":null,"abstract":"<p><p>Ebola virus disease (EVD) causes outbreaks and epidemics in West Africa that persist until today. The envelope glycoprotein of Ebola virus (GP) consists of two subunits, GP1 and GP2, and plays a key role in anchoring or fusing the virus to the host cell in its active form on the virion surface. Toremifene (TOR) is a ligand that mainly acts as an estrogen receptor antagonist; however, a recent study showed a strong and efficient interaction with GP. In this context, we aimed to evaluate the energetic affinity features involved in the interaction between GP and toremifene by computer simulation techniques using the Molecular Fractionation Method with Conjugate Caps (MFCC) scheme and quantum-mechanical (QM) calculations, as well as missense mutations to assess protein stability. We identified ASP522, GLU100, TYR517, THR519, LEU186, LEU515 as the most attractive residues in the EBOV glycoprotein structure that form the binding pocket. We divided toremifene into three regions and evaluated that region i was more important than region iii and region ii for the formation of the TOR-GP1/GP2 complex, which might control the molecular remodeling process of TOR. The mutations that caused more destabilization were ARG134, LEU515, TYR517 and ARG559, while those that caused stabilization were GLU523 and ASP522. TYR517 is a critical residue for the binding of TOR, and is highly conserved among EBOV species. Our results may help to elucidate the mechanism of drug action on the GP protein of the Ebola virus and subsequently develop new pharmacological approaches against EVD.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4753-4769"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139521087","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":"Association between GSTP1 I105V polymorphisms and responses to GSTP1 inhibitor treatment: in silico and in vitro insights.","authors":"Hao Jiao, Aoqi Song, Long Cheng, Dexi Zhou, Jiajie Luan, Hao Lin, Zhirui Zhang","doi":"10.1080/07391102.2024.2309329","DOIUrl":"10.1080/07391102.2024.2309329","url":null,"abstract":"<p><p>Glutathione S-transferase P1 (GSTP1) has gradually become a promising target for cancer prevention and treatment. However, subtle variations in GSTP1 can lead to the occurrence of single nucleotide polymorphisms (SNPs). The correlation between specific genotypes of GSTP1 and the clinical outcome of the disease has been extensively investigated, demonstrating a significant area of research in this field. However, their impact on the responses to GSTP1 inhibitor treatment remains to be elucidated. Among the various SNPs of GSTP1, I105V polymorphisms is the most widely studied. In this study, a silico model of GSTP1 I105V polymorphism was successfully established to predict the changes of binding model and binding affinity between GSTP1 I105(WT) or GSTP1 V105 and ethacrynic acid <i>via</i> molecular docking and molecular dynamics, and ultimately further evaluated for its anticancer effects. The result demonstrated that the binding capacity of ethacrynic acid decreases with the I105V mutation of GSTP1, indicating the changes in its anticancer activities. Cancer cells expressing GSTP1 V105 may exhibit greater tolerance to ethacrynic acid-induced toxicity compared to other genotypes. In summary, this study provides the first evidence that the GSTP1 I105V polymorphism may impact cancer cell sensitivity to its inhibitor through theoretical prediction. Furthermore, a comprehensive understanding of the correlation between GSTP1 I105V polymorphisms and responses to GSTP1 inhibitor treatment would offer valuable insights for future drug development targeting GSTP1 in cancer-related diseases.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4835-4846"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139575729","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}