Journal of Biomolecular Structure & Dynamics最新文献

{"title":"Molecular modeling and cytotoxic activity studies of oxirane-2-carboxylate derivatives.","authors":"Muhammed Tilahun Muhammed, Mustafa Er, Senem Akkoc","doi":"10.1080/07391102.2024.2428826","DOIUrl":"10.1080/07391102.2024.2428826","url":null,"abstract":"<p><p>In this study, five 3-aryloxirane-2-carboxylate derivatives were prepared, and the antiproliferative activities of molecules were screened in lung and colon cancer cell lines. The results showed that molecules had antiproliferative activity on cancerous cells with IC₅₀ values under 100 µM. Furthermore, all of the molecules were found to have a much higher cytotoxic effect than cisplatin in colon cancer cells. The interactions of the relatively active compounds to the crucial enzyme in cancer cell proliferation, cyclin-dependent kinase 1 (CDK1), were investigated using molecular docking. The stability of the resulting CDK1-compound complexes procured from the docking was also assessed through molecular dynamics (MD) simulations. Then, the binding affinity of compounds <b>2-3a</b> and <b>2-3c</b> to the target enzyme was computed by MMPBSA. The molecular docking study demonstrated that the two most active compounds could bind to the enzyme. The binding potential of <b>2-3a</b> is anticipated to be higher as it had one more conventional hydrogen bond and a slightly lower binding energy than compound <b>2-3c</b>. The MD simulation study exhibited that the two compounds formed a stable complex with the enzyme. On the other hand, the MMPBSA energy computation implicated a slightly higher binding affinity for compound <b>2-3c</b> toward the enzyme. Furthermore, electrical and frontier molecular orbital analysis of all of the tested compounds was conducted by density functional theory (DFT) studies. Compound <b>2-3a</b> is anticipated to be the most chemically stable as it gave the highest energy gap value in the DFT analysis.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-12"},"PeriodicalIF":2.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621310","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":"Revisiting <i>Aspergillus terreus</i> MTCC6324 recombinant alcohol oxidase (rAOx): enhanced <i>in-silico</i> insight into structure, function, and substrate sequestration mechanism.","authors":"Mrityunjay Nigam, Mitun Chakraborty","doi":"10.1080/07391102.2024.2424946","DOIUrl":"https://doi.org/10.1080/07391102.2024.2424946","url":null,"abstract":"<p><p>Alcohol oxidase (AOx) enzymes have gained significant attention for their potential in industrial applications due to their unique ability to catalyze irreversible oxidation of diverse alcohol substrates without external co-factors. This study revisits and enhances <i>in-silico</i> work on <i>Aspergillus terreus</i> MTCC6324 recombinant AOx (rAOx) enzyme, combining artificial intelligence (AlphaFold), molecular docking (AutoDock Vina) techniques and Molecular dynamics (MD) simulations (Desmond). Comprehensive sequence analysis revealed a high degree of conservation among 23 AOx amino acid sequences from various <i>Aspergillus</i> species highlights conserved regions, affirming its GXGXXG Rossmann fold motif. AlphaFold-predicted 3D structure of rAOx demonstrated improved stereo-chemical stability compared to I-TASSER predicted structure with 87.6% amino acid residues in most favourable region of Ramachandran plot compared to 79.5%, respectively. Molecular docking revealed the binding affinities of co-factors FAD and diverse alcohol substrates, with cinnamyl alcohol exhibiting robust interaction with rAOx holoenzyme. MD simulations further elucidate the stability and dynamics of rAOx-FAD-cinnamyl alcohol complex over 100 nanoseconds. The simulations showcase FAD's stable binding within the protein core and highlights transient substrate interactions, dissociating within the active site after 75 ns suggesting a substrate sequestration mechanism. The study unveils substrate sequestration mechanism wherein cinnamyl alcohol exhibits temporary binding, leading to quick detachment from active site, mimicking reported exponential kinetics. This study not only validates previous findings but also offers a comprehensive understanding of intricate dynamics governing rAOx enzymatic activity. The improved sequence-to-structure prediction and detailed molecular insights into substrate sequestration provide a valuable foundation for future experimental investigations and rational design of bio-catalytic processes.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-12"},"PeriodicalIF":2.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621341","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":"Targeting transcriptional regulatory protein RfaH with natural compounds to develop novel therapies against <i>Klebsiella pneumoniae</i>.","authors":"Anam Ashraf, Arunabh Choudhary, Mohammad Ali Khan, Saba Noor, Afzal Hussain, Mohamed F Alajmi, Md Imtaiyaz Hassan","doi":"10.1080/07391102.2024.2427376","DOIUrl":"10.1080/07391102.2024.2427376","url":null,"abstract":"<p><p>The growing threat of antibiotic-resistant <i>K. pneumoniae</i> infections demands novel treatment strategies. This study focuses on the transcriptional regulatory protein RfaH, a protein crucial for the bacteria's virulence by promoting gene expression for its capsule, cell wall, and pilus. As <i>K. pneumoniae</i> becomes resistant to existing antibiotics, targeting RfaH with specific inhibitors offers a promising alternative. The diverse benefits of natural compounds, including efficacy against microbial diseases, modulation of inflammatory processes, and potential in cancer therapy, have led to their increasing use in medicine. Through natural compound screening, we aimed to identify potential RfaH inhibitors and understand their interactions with the active site pocket of RfaH. Disrupting interactions of specific residues in RfaH by ligand binding could offer a means to interfere with its function selectively. We found that Naringenin and Quercetin have a strong binding affinity for RfaH β'CH binding pocket and form stable complexes, as evident from the MD simulation studies. The binding affinity of Naringenin and Quercetin was further validated experimentally by fluorescence measurements. This knowledge can be used to design potent and selective RfaH inhibitors for a new therapeutic approach to combat <i>K. pneumoniae</i> infections and address the urgent need for effective treatments.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-13"},"PeriodicalIF":2.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621345","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, synthesis, biological evaluation, and molecular modeling studies of some quinazolin-4(3<i>H</i>)-one-benzenesulfonamide hybrids as potential α-glucosidase inhibitors.","authors":"Emre Kadir Ayan, Güneş Çoban, Zeynep Soyer","doi":"10.1080/07391102.2024.2427373","DOIUrl":"https://doi.org/10.1080/07391102.2024.2427373","url":null,"abstract":"<p><p>Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia, posing serious health risks and becoming increasingly prevalent. Prolonged hyperglycemia can lead to complications such as nephropathy, neuropathy, retinopathy, cardiovascular damage, and blindness. Controlling hyperglycemia through α-glucosidase inhibitors, which slow down carbohydrate breakdown, is an effective treatment strategy. However, current inhibitors like acarbose, voglibose, and miglitol while used to manage type 2 diabetes, have significant side effects. Therefore, developing new α-glucosidase inhibitors that are more effective and have fewer side effects is crucial. In this study, a series of novel quinazolin-4(3<i>H</i>)-one-benzenesulfonamide hybrid compounds were designed, synthesized, and evaluated for <i>in vitro</i> α-glucosidase inhibitory activity. The compounds showed higher enzyme inhibition potency, with IC₅₀ values ranging between 129.2 ± 0.5 and 558.7 ± 13.7 µM, compared to acarbose (IC₅₀=814.3 ± 13.5 µM). Among the tested compounds, compound <b>10</b>, bearing a 4-chlorophenyl ring on the nitrogen atom of the sulfonamide group, was the most active, with an IC₅₀ value of 129.2 ± 0.5 µM. Enzyme kinetics analyses and molecular modeling studies were conducted to understand their inhibition mechanisms and interactions with the enzyme. The kinetic studies revealed a mixed-type inhibition model, indicating that the compounds bind to the enzyme-substrate complex with higher affinity than to the free enzyme. Molecular modeling results confirmed these findings. Additionally, <i>in silico</i> prediction studies showed that the selected compounds have favourable physicochemical and drug-like properties. These results suggest these compounds have potential for further optimization and development as effective α-glucosidase inhibitors for diabetes treatment.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-21"},"PeriodicalIF":2.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621277","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 targets and biomarkers for doxorubicin-induced cardiotoxicity in humans: implications drawn from toxicogenomic data and molecular modelling.","authors":"Fuat Karakuş, Abdulilah Ece, Burak Kuzu","doi":"10.1080/07391102.2024.2427380","DOIUrl":"https://doi.org/10.1080/07391102.2024.2427380","url":null,"abstract":"<p><p>The doxorubicin-induced cardiotoxicity continues to be a life-threatening adverse effect in the clinic. Doxorubicin-induced acute cardiotoxicity is reversible, whereas chronic cardiotoxicity is irreversible, leading to dilated cardiomyopathy and heart failure. The aim of this study was to identify the molecular mechanisms associated with doxorubicin metabolites in doxorubicin-induced chronic cardiotoxicity. For this purpose, literature searches and <i>in silico</i> toxicogenomic analyses were conducted using various tools, including the Comparative Toxicogenomic Database, GeneMANIA, Metascape, MIENTURNET, ChEA3, and AutoDock. Additionally, molecular dynamics simulations were performed for 500 ns using Schrödinger software to assess the stability and dynamics of the representative docked complexes. We observed that doxorubicin biotransformed into five metabolites in the human heart and identified 11 common genes related to doxorubicin, its metabolites, dilated cardiomyopathy, and heart failure. Our findings revealed that doxorubicin and its metabolites primarily exhibited binding affinity to the beta-1 adrenergic receptor and fatty acid synthase. Furthermore, we identified several key transcription factors, especially the Homeobox protein Nkx-2.6, and hsa-miR-183-3p associated with this cardiotoxicity. Finally, we observed that, in addition to doxorubicinol, 7-deoxidoxorubicinone, another metabolite of doxorubicin, may also contribute to this cardiotoxicity. These findings contribute to our understanding of the processes underlying doxorubicin-induced chronic cardiotoxicity.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-13"},"PeriodicalIF":2.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621315","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":"Discerning potent CSF-1r inhibitors for targeting and therapy of neuroinflammation using computational approaches.","authors":"Anupriya Adhikari, Anwesh Pandey","doi":"10.1080/07391102.2024.2427366","DOIUrl":"https://doi.org/10.1080/07391102.2024.2427366","url":null,"abstract":"<p><p>Microglia, the primary cellular mediator of neuroinflammation, plays a pivotal role in numerous neurological disorders. Precise and non-invasive quantification of microglia is of paramount importance. Despite various investigations into cell-specific biomarkers for assessing neuroinflammation, many suffer from poor cellular specificity and low signal-to-noise ratios. Colony-stimulating factor-1 receptor (CSF-1R), also known as FMS kinase, has emerged as a promising neuroinflammation biomarker with significant relevance to inflammatory diseases. Additionally, CSF-1R inhibitors (CSF-1Ri) have shown therapeutic potential in central nervous system (CNS) pathological conditions by depleting microglia. Therefore, the development of more specific CSF-1R inhibitors for targeting and treating various CNS insults and neurological disorders is imperative. This study focuses on the search for novel CSF-1R inhibitors. Based on the literature on CSF-1R inhibitors, we proposed and investigated ten ligands as novel CSF-1R inhibitors. Among these, the top three ligands, selected based on their maximum binding scores in docking calculations, are subjected to 100 nanoseconds of molecular dynamics (MD) simulation, alongside three reference ligands. All protein-ligand complexes remain stable throughout the dynamics and exhibit minimal fluctuations during the analysis. The results obtained through this study may prove significant for the future design of CSF-1R inhibitors with potential applications in the field of biomedicine.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-12"},"PeriodicalIF":2.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621279","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":"Molecular dynamics simulations provide insights into ULK-101 potency and selectivity toward autophagic kinases ULK1/2.","authors":"Robert M Vaughan, Bradley M Dickson, Katie R Martin, Jeffrey P MacKeigan","doi":"10.1080/07391102.2024.2425833","DOIUrl":"10.1080/07391102.2024.2425833","url":null,"abstract":"<p><p>Kinase domains are highly conserved within proteins in both sequence and structure. Many factors, including phosphorylation, amino acid substitutions or mutations, and small molecule inhibitor binding, influence conformations of the kinase domain and enzymatic activity. ULK1 and ULK2 are serine/threonine kinases that serve important roles in autophagy, an intracellular recycling process capable of degrading proteins and organelles <i>via</i> fusion with lysosomes. ULK1/2 are emerging as therapeutic targets in human cancer, particularly KRAS-driven malignancies. Here, we performed molecular dynamics (MD) simulations to hypothesize bound poses for the ULK1/2 small molecule inhibitor, ULK-101. We observed stable bound states for ULK-101 to the adenosine triphosphate (ATP)-binding site of ULK2, coordinated by hydrogen bonding with the hinge backbone and the catalytic lysine sidechain. Notably, ULK-101 occupies a hydrophobic pocket associated with the N-terminus of the αC-helix. Large movements in the phosphate-binding loop (P-loop) are also associated with ULK-101 inhibitor binding and exit from ULK2. Together, our data support a model to explain ULK-101 potency toward ULK1/2.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-8"},"PeriodicalIF":2.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621298","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":"Discovering Lassa virus nucleoprotein inhibitors via in silico drug repositioning approach.","authors":"Handan Şimşek, Şeref Gül","doi":"10.1080/07391102.2024.2427370","DOIUrl":"https://doi.org/10.1080/07391102.2024.2427370","url":null,"abstract":"<p><p>Lassa fever, caused by the zoonotic Lassa virus (LASV), poses a significant health threat in Africa, leading to thousands of infections and deaths annually and has the potential to spread to other parts of the world. Despite the urgency for effective treatments, there are currently no approved drugs or vaccines for Lassa fever. LASV possesses a unique negative-sense RNA genome, and NP plays a crucial role in viral assembly and infection. Crystallographic analysis reveals distinct domains in NP, with the N-terminal domain involved in RNA binding and the C-terminal domain exhibiting exoribonuclease activity, suppressing type I interferon-mediated immune responses. This study explores the potential of repurposing existing FDA-approved drugs by targeting the N-terminal domain of LASV's nucleoprotein (NP). Docking simulations and molecular dynamics experiments were conducted, revealing promising interactions between NP and widely used and well tolerated drugs such as metacycline, eltrombopag, glimepiride, lurasidone, paliperidone, prednisone, doxazosin, flavin mononucleotide, and pimozide. These drugs exhibited stable binding throughout 100 ns simulations, with interactions resembling those observed with the natural ligand, dTTP. Binding free energy calculations identified key amino acids, particularly Phe176 and Arg300, as crucial for drug-NP interactions. Notably, drugs like FMN, prednisone, metacycline, pimozide, and glimepiride displayed binding affinities comparable to dTTP, suggesting their potential as LASV inhibitors. The study underscores the importance of further experimental and clinical validation of these in silico findings. The identified drugs present promising candidates for potential treatments for Lassa fever, addressing the current gap in approved therapeutics for this life-threatening infectious disease.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-21"},"PeriodicalIF":2.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621292","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":"Molecular insights from structural dynamics of HER2-inhibitor complexes pave the way for new breast cancer drugs.","authors":"Kanchan Lata Tripathi, Ayushi Chaudhary, Aftab Alam, Divyanshi Shukla, Rima Bhardwaj, Himani Badoni","doi":"10.1080/07391102.2024.2425835","DOIUrl":"https://doi.org/10.1080/07391102.2024.2425835","url":null,"abstract":"<p><p>The human epidermal growth factor receptor 2 (HER2) is closely associated with the development and progression of breast cancer, making it a critical target for therapeutic interventions. In this study, we employed a comprehensive computational drug discovery strategy to identify potential inhibitors of HER2. Our approach combined virtual screening, re-docking procedures, molecular dynamics (MD) simulations, and free energy landscape analysis using principal component analysis (PCA). From the extensive PubChem library, we initially screened 733 compounds for their binding potential to HER2, using docking scores as a primary filter. These scores ranged notably from -11.172 to -7.028 kcal/mol, indicating substantial binding capacities. Following this screening, we selected four promising compounds (PubChem CID 166029206, 166544027, 21031510, and 11712721) along with a control compound (70I) for in-depth analysis. Utilizing the Amber software suite for MD simulations, we conducted 200-nanosecond simulations to assess the interactions and binding efficiencies of these selected compounds with HER2. We analysed the molecular interactions through various parameters such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), and hydrogen bond formation patterns, free binding energy calculations. The PCA-based free energy landscape analysis revealed that these compounds consistently occupied a distinct low-energy basin, indicating their high stability and strong binding affinity for the HER2. This detailed analysis provided insights into the stability and conformational dynamics of these potential inhibitors when bound to the HER2. Our findings pave the way for further experimental validation and development of these compounds as therapeutic agents in breast cancer treatment.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-14"},"PeriodicalIF":2.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621304","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":"β-1,3-glucan from <i>Euglena gracilis</i>: a promising epidrug targeting epigenetic regulators PRMTs and SIRTs for therapeutic applications in ovarian cancer.","authors":"Varsha Virendra Palol, Kamran Waidha, Balasubramanian Moovarkumudalvan, Navya Valavath Baburajan, Suresh Kumar Saravanan, Divya Lakshmanan, Veni Subramanyam, Raj Kumar Chinnadurai","doi":"10.1080/07391102.2024.2425832","DOIUrl":"https://doi.org/10.1080/07391102.2024.2425832","url":null,"abstract":"<p><p>Natural products serve as a valuable resource in drug discovery and the identification of bioactive molecules in the field of epimedicine, which targets epigenetic regulator enzymes through epidrugs. In this study, β-1,3-glucan (BG), a natural storage polysaccharide in <i>Euglena gracilis,</i> a well-known immunostimulatory agent, is propounded as a promising epidrug. To elucidate the therapeutic efficacy of BG against ovarian cancer, the molecular interactions between BG and epigenetic regulators, Protein Arginine Methyltransferases (PRMTs) and Sirtuins (SIRTs) were investigated using computational methods followed by <i>in vitro</i> gene expression studies in SKOV-3 ovarian cancer cell line. The binding energies of PRMT5 and SIRT5 against BG were observed as -65.5 and -68.2 kcal/mol, respectively. The <i>in vitro</i> cytotoxic effects of BG against human ovarian cancer cell line, SKOV-3 showed an IC₅₀ of 150 µg/mL at 48 h. Significant epigenetic modifications were observed to be influenced by BG which increased the gene expression of PRMT5, SIRT5 and Nrf2 to 0.3, 0.5, and 0.7 fold-change respectively, while the Nrf1/2 plasmid showed reduced reporter activity by 29%. Collectively, both <i>in silico</i> and <i>in vitro</i> studies provided valuable insights into the epigenetic regulation of PRMT5 and SIRT5 by BG <i>via</i> Nrf1/2. Nonetheless, further preclinical and clinical investigations are essential to validate the therapeutic properties of BG as an epidrug against ovarian cancer.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-16"},"PeriodicalIF":2.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621348","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}