Journal of Biomolecular Structure & Dynamics最新文献_第7页

Copper(II)-photocatalyzed Hydrocarboxylation of Schiff bases with CO₂: antimicrobial evaluation and in silico studies of Schiff bases and unnatural α-amino acids. Copper(II)-photocatalyzed Hydrocarboxylation of Schiff bases with CO2: antimicrobial evaluation and in silico studies of Schiff bases and unnatural α-amino acids.

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-01 Epub Date: 2024-01-08 DOI: 10.1080/07391102.2024.2301765

Allen T Gordon, Eric C Hosten, Sandy van Vuuren, Adeniyi S Ogunlaja

{"title":"Copper(II)-photocatalyzed Hydrocarboxylation of Schiff bases with CO2: antimicrobial evaluation and in silico studies of Schiff bases and unnatural α-amino acids.","authors":"Allen T Gordon, Eric C Hosten, Sandy van Vuuren, Adeniyi S Ogunlaja","doi":"10.1080/07391102.2024.2301765","DOIUrl":"10.1080/07391102.2024.2301765","url":null,"abstract":"We synthesized and characterized two copper(II) complexes: [CuL2Cl]Cl and [CuL'2Cl]Cl, where L = 2,2'-bipyridine and L' = 4,4'-dimethyl-2,2'-bipyridine. We evaluated their photocatalytic hydrocarboxylation properties on a series of synthesized Schiff bases (SBs): (E)-1-(4-((5-bromo-2-hydroxybenzylidene)amino)phenyl)ethanone (SB1), (E)-N-(4-(dimethylamino)benzylidene)benzo[d]thiazol-2-amine (SB2), (E)-4-Bromo-2-((thiazol-2-ylimino)methyl)phenol (SB3), and (E)-4-((5-bromo-2-hydroxybenzylidene)amino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one (SB4). Under mild photocatalytic reaction conditions (room temperature, 1 atm CO2, 30-watt Blue LED light), the derivatives of α-amino acids UAA1-4 were obtained with yields ranging from 5% to 44%. Experimental results demonstrated that [CuL2Cl]Cl exhibited superior photocatalytic efficiency compared to [CuL'2Cl]Cl, attributed to favourable electronic properties. In silico studies revealed strong binding strengths with E. faecalis DHFR (4M7U) for docked Schiff bases (SB) and unnatural α-amino acids (UAAs). In vitro studies further demonstrated significant antimicrobial and antifungal activity for SB2, SB3, and SB4, while none of the synthesized UAAs exhibited such properties, primarily due to the electronic and binding properties of these molecules.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4201-4214"},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403030","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}

引用次数: 0

Investigating the combined effect of copper, zinc, and iron ions on truncated and full-length Aβ peptides: insights from molecular dynamics simulation. 研究铜、锌和铁离子对截短和全长 Aβ 肽的综合影响：分子动力学模拟的启示。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-01 Epub Date: 2024-01-08 DOI: 10.1080/07391102.2024.2301755

Mona Sohrabi, Mohammad Reza Bozorgmehr, Mohammad Momen-Heravi

{"title":"Investigating the combined effect of copper, zinc, and iron ions on truncated and full-length Aβ peptides: insights from molecular dynamics simulation.","authors":"Mona Sohrabi, Mohammad Reza Bozorgmehr, Mohammad Momen-Heravi","doi":"10.1080/07391102.2024.2301755","DOIUrl":"10.1080/07391102.2024.2301755","url":null,"abstract":"The truncated Aβ1 - 16 peptide containing the metal-binding domain is frequently used in in silico and experimental investigations because it is more soluble and thus more suitable for studies in solution and does not form amyloids. Several spectroscopic studies have shown that the metal binding of Aβ1 - 16 is very similar to that of the full-length Aβ1 - 42. However, since small changes can have a significant impact on aggregation, further experimental and theoretical are needed to elucidate the detailed structures of truncated and full-length Aβ. In this research, the binding of copper ion to the Aβ1 - 16 and Aβ1 - 42 has been studied by molecular dynamics simulation method. To investigate the effect of copper ion on beta-amyloid peptide structure, the simulations were repeated in the copper and zinc ions, copper and iron binary system, and the copper, zinc and iron ions ternary system. The conformation factor was calculated to calculate the binding affinity of copper ion to beta-amyloid peptide residues. The results showed that the initial 16 residues of the beta-amyloid peptide have high binding affinity for copper ions, and histidine 13 and histidine 14 have significantly higher binding affinity for copper ions in all studied systems. Zinc and iron ions were found to reduce the conformational factor of peptide residues in binding to copper ions, and the aggregation tendency was lower in the truncated structure. The SASA results suggest that the side chains of peptide residues are more affected by shortening and the presence of ions.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4165-4173"},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139377688","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}

引用次数: 0

QM/MM investigation of the discriminatory pre-transfer editing mechanism operated by Lysyl-tRNA synthetase. 赖氨酰-tRNA 合成酶的鉴别转移前编辑机制的 QM/MM 研究。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-01 Epub Date: 2024-01-10 DOI: 10.1080/07391102.2023.2301054

Bogdan F Ion, Mohamed M Aboelnga, James W Gauld

{"title":"QM/MM investigation of the discriminatory pre-transfer editing mechanism operated by Lysyl-tRNA synthetase.","authors":"Bogdan F Ion, Mohamed M Aboelnga, James W Gauld","doi":"10.1080/07391102.2023.2301054","DOIUrl":"10.1080/07391102.2023.2301054","url":null,"abstract":"Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes that remarkable facilitate the aminoacylation process during translation. With a high fidelity, the mischarged tRNA is prevented through implementing pre- and post-transfer proofreading mechanisms. For instance, Lysine-tRNA synthetase charges the native substrate, lysine, to its cognate tRNA. In spite of the great structural similarity between lysine to the noncognate and toxic ornithine, with the side chain of lysine being only one methylene group longer, LysRS is able to achieve this discrimination with a high efficiency. In this work, the hybrid quantum mechanics/molecular mechanics (QM/MM) investigation was applied to probe the pre-transfer editing mechanism catalyzed by lysyl-tRNA synthetase to reject the noncognte aminoacyl, L-ornityl (Orn), compared to the cognate substrate, L-lysyl. Particularly, the self-cyclization pre-transfer editing mechanism was explored for the two substrates. The substrate-assisted self-cyclization editing of Orn-AMP, where its phosphate moiety acts as the catalytic base, is found to be the rate-determining step with an energy barrier of 101.2 kJ mol-1. Meanwhile, the corresponding rate-limiting pathway for the native Lys-AMP lies at 140.2 kJ mol-1. This observation clearly indicated the infeasibility of this catalytic scenario in the presence of the native substrate. Interestingly, a thermodynamically favorable cyclic product of -92.9 kJ mol-1 with respect to the aminoacyl reactant complex demonstrated evidence of a successful pre-transfer editing. This reaction resulted in the discharge of the on-cognate -ornithine derivative from LysU's active site. These valuable mechanistic insights are valuable to enrich our knowledge of this extremely efficient and specific catalytic machinery of LysRS.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4004-4012"},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403047","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}

引用次数: 0

Identification of phytochemicals from genus Potentilla as estrogen receptor-α inhibitors through molecular docking, molecular dynamic simulation and DFT calculations. 通过分子对接、分子动力学模拟和DFT计算等方法鉴定蕨草属植物雌激素受体-α抑制剂。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-04-30 DOI: 10.1080/07391102.2025.2498622

Amit Kumar, Nehal Purohit, Praval Pratap Singh, Kailash Jangid, Vijay Kumar, Jare Shrikrushna Bharat, Sudip Chakraborty, Vinod Kumar, Vikas Jaitak

{"title":"Identification of phytochemicals from genus Potentilla as estrogen receptor-α inhibitors through molecular docking, molecular dynamic simulation and DFT calculations.","authors":"Amit Kumar, Nehal Purohit, Praval Pratap Singh, Kailash Jangid, Vijay Kumar, Jare Shrikrushna Bharat, Sudip Chakraborty, Vinod Kumar, Vikas Jaitak","doi":"10.1080/07391102.2025.2498622","DOIUrl":"https://doi.org/10.1080/07391102.2025.2498622","url":null,"abstract":"Breast cancer is among the most prevalent causes of death in women worldwide. About 70-75% of these cancers are hormone-dependent, expressing estrogen receptors (ERs), mainly ER-α, making it an essential target for managing breast cancer. Potentilla genus has been traditionally used worldwide for its diverse biological activities, including antidiabetic, anti-inflammatory, antioxidant, etc. In the present study, phytochemicals isolated from various species of the Potentilla species were evaluated for their in silico ER-α inhibitory activity through molecular docking, molecular dynamic simulation, Density Functional Theory calculations and free energy calculations. Four hundred seventy-one molecules were used through ligand preparation and docked inside the generated grid on ER-α protein cavity and the standard drug tamoxifen. Fourteen molecules have shown better dock (-14.42 to -12.57 kcal/mol) scores than tamoxifen (-10.71 kcal/mol). Most of the molecules belong to the category of flavonoid glycosides. Molecules with good binding free energy (-78.81 to -12.94 kcal/mol) indicate stability inside the binding pocket. Further, based on dock score, pharmacokinetic parameters, and binding free energy, two hit molecules, 1 and 2, were selected for their molecular dynamic simulation, MM/PBSA and DFT calculations for assessing their stability and structural dynamics inside the binding cavity as well as their reactivity. Through MD simulation analysis, it was evaluated that Compound 1 could distort the protein to a greater extent. In contrast, compound 2 was stable throughout the simulation time of 150 ns and can be further explored in vitro and in vivo studies as ER-α inhibitors in breast cancer.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-17"},"PeriodicalIF":2.7,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009074","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}

引用次数: 0

Identification of potential casein kinase I isoform epsilon inhibitors from phytoconstituents: implications for targeted anticancer therapeutics. 从植物成分中鉴定潜在酪蛋白激酶I异构体epsilon抑制剂：对靶向抗癌治疗的意义。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-04-29 DOI: 10.1080/07391102.2025.2497462

Mohammed Ageeli Hakami, Ali Hazazi, Mohammad Ali Abdullah Almoyad, Shadma Wahab, Mohammed H Alqarni, Ahmed I Foudah, Amirah Albaqami, Mohammad Khalid

{"title":"Identification of potential casein kinase I isoform epsilon inhibitors from phytoconstituents: implications for targeted anticancer therapeutics.","authors":"Mohammed Ageeli Hakami, Ali Hazazi, Mohammad Ali Abdullah Almoyad, Shadma Wahab, Mohammed H Alqarni, Ahmed I Foudah, Amirah Albaqami, Mohammad Khalid","doi":"10.1080/07391102.2025.2497462","DOIUrl":"https://doi.org/10.1080/07391102.2025.2497462","url":null,"abstract":"Casein kinase I isoform epsilon (CK1ε) demonstrates significant implications in cancer pathogenesis, influencing key cellular processes linked to oncogenesis. Its regulatory roles in cell survival, proliferation, and modulation of oncogenic pathways highlight CK1ε as a potential target for therapeutic strategies in diverse cancer types. In this research, a virtual screening of phytoconstituents from the IMPPAT2.0 database was conducted to find potential inhibitors targeting CK1ε. Initially, compounds adhering to Lipinski's rule of five were retrieved, followed by filtering based on binding affinities and subsequent interaction analyses to refine the selection. Finally, two compounds, Chrysin-7-O-Glucuronide and Rhodiolin, demonstrated considerable affinities with specific interactions at the CK1ε ATP binding site (involving SER17, SER19, and LYS38), forming hydrogen bonds, and were identified for further analysis via PASS server. Employing all-atom molecular dynamic (MD) simulations for 200 ns, structural deviation, residual fluctuation, compactness by radius of gyration, solvent accessible surface area calculation, principal component analysis, and free energy landscapes, were conducted. These findings suggest that Chrysin-7-O-Glucuronide and Rhodiolin warrant further investigation in experimental and clinical research as potential candidates for developing anticancer therapeutics targeting CK1ε kinase.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-13"},"PeriodicalIF":2.7,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970137","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}

引用次数: 0

A spectroscopic, molecular docking and molecular dynamic simulation study on the interaction of human hemoglobin with 2,4-dichlorophenoxyacetic acid. 人血红蛋白与2,4-二氯苯氧乙酸相互作用的光谱、分子对接和分子动力学模拟研究。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-04-28 DOI: 10.1080/07391102.2025.2496770

Ruhul Quds, Md Amiruddin Hashmi, Monika Sharma, Riaz Mahmood

{"title":"A spectroscopic, molecular docking and molecular dynamic simulation study on the interaction of human hemoglobin with 2,4-dichlorophenoxyacetic acid.","authors":"Ruhul Quds, Md Amiruddin Hashmi, Monika Sharma, Riaz Mahmood","doi":"10.1080/07391102.2025.2496770","DOIUrl":"https://doi.org/10.1080/07391102.2025.2496770","url":null,"abstract":"2,4-Dichlorophenoxyacetic acid (2,4-D) is a systemic herbicide widely used to control dicotyledonous weeds. The general population is routinely exposed to 2,4-D due to consumption of contaminated food and water. 2,4-D is known to damage cellular components in human erythrocytes. This study investigated in detail the interaction of 2,4-D with human hemoglobin (Hb), the major protein in erythrocytes (>95%), and characterized the binding properties utilizing multi-spectrometric and in silico techniques. The UV-visible spectra suggested that 2,4-D interacts with Hb. The fluorescence quenching studies at three different temperatures further showed the binding of 2,4-D to Hb and the formation of a ground-state complex. The results indicated that 2,4-D binds spontaneously to a single moderate-affinity binding site on Hb. Furthermore, the binding process involved van der Waals forces and hydrogen bonding. Circular dichroism and synchronous fluorescence spectra showed that the binding of 2,4-D altered the conformation of Hb and decreased the polarity around its tryptophan residues. 2,4-D binding inhibited the inherent esterase activity of Hb. Computational analysis demonstrated that the Hb-2,4-D complex was stable and identified the amino acid residues at the binding site. Thus, 2,4-D interacts with Hb, modifies the protein conformation and consequently impairs its functions.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-13"},"PeriodicalIF":2.7,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992700","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}

引用次数: 0

Designing highly efficient heterocyclic inhibitors for SARS-CoV-2 3C-like proteinase: a comprehensive in silico study. 设计高效的sars - cov - 23c样蛋白酶杂环抑制剂：一项全面的计算机研究。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-04-27 DOI: 10.1080/07391102.2025.2494842

Nabil Nor, Soukaina Zahm, Habib El Alaoui El Abdallaoui, Said Kerraj, Naima Naji, Noureddine Mazoir, Najia Komiha, Khadija Marakchi, Mohammed Salah

{"title":"Designing highly efficient heterocyclic inhibitors for SARS-CoV-2 3C-like proteinase: a comprehensive in silico study.","authors":"Nabil Nor, Soukaina Zahm, Habib El Alaoui El Abdallaoui, Said Kerraj, Naima Naji, Noureddine Mazoir, Najia Komiha, Khadija Marakchi, Mohammed Salah","doi":"10.1080/07391102.2025.2494842","DOIUrl":"https://doi.org/10.1080/07391102.2025.2494842","url":null,"abstract":"To address the limitations of current COVID-19 treatments, we conducted an integrated in-silico investigation to design potential drugs with proven efficacy against the virus. We developed Quantitative Structure-Activity Relationship (QSAR) models using a database of 63 Aromatic heterocyclic compounds, focusing on key parameters Effective Diameter (ED) and Diameter Maximum (DM). Our models, utilizing multi-linear regression (MLR) and Artificial Neural Network (ANN), were validated according to OECD principles and successfully used to predict unexplored aromatic heterocyclic compounds with Pyridine Cores. Compound 4 (Dexbrompheniramine) exhibited high inhibition against the SARS coronavirus 3 C-like protease, leading to the design of two new molecules (compounds 15 and 16) with enhanced activity based on structural enhancements from the QSAR model. Docking studies and molecular dynamics simulations confirmed the improved binding energies and stability of compounds 15 and 16, with compound 15 showing remarkable stability and strong binding affinity with the 3 C-like proteinase (1P9U). This comprehensive in-silico review identifies compound 15 as a promising candidate for experimental evaluation as a potential COVID-19 drug, highlighting a significant advancement in our battle against the pandemic.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-9"},"PeriodicalIF":2.7,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992946","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}

引用次数: 0

Elucidating the interaction between MTDH, an oncoprotein with UPR signalling molecule IRE1α under cellular stress. 阐明肿瘤蛋白MTDH与UPR信号分子IRE1α在细胞应激下的相互作用。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-04-26 DOI: 10.1080/07391102.2025.2487697

Khalida Ramzan, Younis Hazari, Arif Bashir, Younis Majeed, Ariha Ashraf, Khalid Majid Fazili

{"title":"Elucidating the interaction between MTDH, an oncoprotein with UPR signalling molecule IRE1α under cellular stress.","authors":"Khalida Ramzan, Younis Hazari, Arif Bashir, Younis Majeed, Ariha Ashraf, Khalid Majid Fazili","doi":"10.1080/07391102.2025.2487697","DOIUrl":"https://doi.org/10.1080/07391102.2025.2487697","url":null,"abstract":"IRE1α (inositol-requiring enzyme type 1) is one of the primary sensor arms of UPR signalling pathway with special ability to detect unfolded/misfolded proteins in the ER lumen. It is a bifunctional protein with kinase and endoribonuclease activity, playing a crucial role in managing ER stress. The C-terminal domain of IRE1α, facing towards the cytosol, acts as a scaffold for various effector proteins to regulate IRE1α activity. Our previous mass spectroscopic studies has revealed Metadherin (MTDH) as one of the binding partner of IRE1α. MTDH is an oncoprotein implicated in cancer metastasis and survival, affecting various cell signalling pathways to drive cancer progression. The presence of this protein in the immune complex in our IRE1α driven immunoprecipitation experiments of stressed cells was significant as the UPR is believed to facilitate cell apoptosis during prolonged stress, which is compromised in cancerous cells to allow metastasis. This prompted us to study and explore the interaction between the two proteins IRE1α and MTDH, a positive interaction pointing to a cross talk between the homeostatic and metastatic signalling pathways. Various experiments, including co-immunoprecipitation, Yeast-two Hybrid assay, and bioinformatics analyses established a positive interaction between IRE1α and MTDH supporting the argument that these proteins interact and might influence IRE1α's role in cellular stress response.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-15"},"PeriodicalIF":2.7,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009966","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}

引用次数: 0

Exploring the mechanism of Cynanchum paniculatum (Bunge) Kitag's therapeutic strategy for rheumatoid arthritis: integrating network pharmacology, molecular docking and in vivo experiments. 结合网络药理学、分子对接和体内实验，探讨金钱菊治疗类风湿性关节炎的机制。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-04-24 DOI: 10.1080/07391102.2025.2494840

Chen Wang, Wangxiang Huang, Qianzi Chen, Chenying Yang, Haiting Zhu, Xiya Chen, Qiyi He, Xiaodong Yu

{"title":"Exploring the mechanism of Cynanchum paniculatum (Bunge) Kitag's therapeutic strategy for rheumatoid arthritis: integrating network pharmacology, molecular docking and in vivo experiments.","authors":"Chen Wang, Wangxiang Huang, Qianzi Chen, Chenying Yang, Haiting Zhu, Xiya Chen, Qiyi He, Xiaodong Yu","doi":"10.1080/07391102.2025.2494840","DOIUrl":"https://doi.org/10.1080/07391102.2025.2494840","url":null,"abstract":"Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by joint swelling, cartilage degradation, and joint deformity. The traditional Chinese herb Cynanchum paniculatum (Bunge) Kitag has been utilized in the management of RA, but the underlying mechanisms are unknown. This study utilized network pharmacology analysis to identify 26 active compounds associated with RA treatment and elucidate their interactions with 23 critical targets linked to RA. Subsequently, molecular docking studies revealed eight compounds with the capacity to bind to multiple key targets, with butyl isobutyl phthalate and geranyl acetone emerging as the most promising candidates based on their drug-likeness properties. To validate these findings, a rat model of adjuvant-induced arthritis was employed. Oral administration of geranyl acetone led to a significant reduction in paw swelling and pro-inflammatory markers, including TNF-α, IL-6, IL-1β, and MPO. Furthermore, it resulted in histological improvements in ankle tissues, all without adverse effects on weight or immune organs. Mechanistically, geranyl acetone was found to impede the progression of RA by modulating the TLR4/MyD88/NF-κB signaling pathway. In conclusion, C. paniculatum demonstrates substantial therapeutic potential for RA due to its multi-target and multi-pathway activities. Moreover, geranyl acetone, when used as a standalone agent, exhibits significant promise in alleviating RA symptoms, offering a compelling avenue for further research and potential clinical applications.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-15"},"PeriodicalIF":2.7,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009338","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}

引用次数: 0

Nitration at tyrosine 61 residue of Macrophomina phaseolina secretory glucanase brings a conformational change through a lock-unlock mechanism. 在菜绿巨藻分泌葡聚糖酶的酪氨酸61残基上硝化，通过锁-解锁机制引起构象变化。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-04-23 DOI: 10.1080/07391102.2025.2494845

Nibedita Ray Chaudhuri, Nilanjan Sinha, Shubhra Ghosh Dastidar, Sanjay Ghosh

{"title":"Nitration at tyrosine 61 residue of Macrophomina phaseolina secretory glucanase brings a conformational change through a lock-unlock mechanism.","authors":"Nibedita Ray Chaudhuri, Nilanjan Sinha, Shubhra Ghosh Dastidar, Sanjay Ghosh","doi":"10.1080/07391102.2025.2494845","DOIUrl":"https://doi.org/10.1080/07391102.2025.2494845","url":null,"abstract":"Nitration of Tyrosine residue, is a footprint of its preceding nitrosative stress conditions that make nitric oxide-derived oxidants abundant. Such a post-translational chemical modification, as byproduct of a stressed condition, could be an onset of a functional pathway. Macrophomina phaseolina, which is a global devastating necrotrophic fungal pathogen, is hereby reported to have at least nine tyrosine nitrated proteins in its secretome; among them Glucanase is an important virulence secretory protein that gets nitrated at Y61. The immediate impact on the Glucanase is likely to be a perturbation on the protein itself, which would prepare the protein to function, i.e. structurally ready to recognize binding partners which could not get recognized otherwise. Y61 nitration stabilizes the enzyme's structure, particularly, its central channel within the enzyme's core. Its mechanical consequences operate at both local and global scales. The key driving factor is a positional switch of Y61 which is triggered by charge-charge repulsion between D63 and Y61 upon nitration. This switching is responsible for a critical 'lock-unlock' mechanism at the upper junction of the channel that regulates solvent exposure, underscoring Y61's pivotal role as a gating residue for the channel. While it's 'gating-in' at the junction unlocks and distorts the channel shape, its 'gating-out' locks the channel into a well-guarded conformation systematically regulating its overall exposure that can potentiate precise substrate routing towards the active site. The findings suggest that Y61 nitration-induced conformational changes have the potential to drive enzyme activation, representing a novel insight into the behavior of M. phaseolina glucanase.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-11"},"PeriodicalIF":2.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016269","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}

引用次数: 0