Journal of Biomolecular Structure & Dynamics最新文献_第2页

Integrating transcriptomics with disease-gene network and identification of EGFR kinase target: inhibitor discovery through virtual screening of natural compounds for brain cancer therapy. 整合转录组学与疾病基因网络和EGFR激酶靶点的鉴定：通过虚拟筛选天然化合物发现脑癌治疗抑制剂。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-08 DOI: 10.1080/07391102.2025.2501672

Mohd Rehan, Wejdan M AlZahrani, Firoz Ahmed, Mohammad Imran Khan, Hifzur Rahman Ansari, Shazi Shakil, Moustafa E El-Araby, Salman Hosawi, Mohammad Saleem

{"title":"Integrating transcriptomics with disease-gene network and identification of EGFR kinase target: inhibitor discovery through virtual screening of natural compounds for brain cancer therapy.","authors":"Mohd Rehan, Wejdan M AlZahrani, Firoz Ahmed, Mohammad Imran Khan, Hifzur Rahman Ansari, Shazi Shakil, Moustafa E El-Araby, Salman Hosawi, Mohammad Saleem","doi":"10.1080/07391102.2025.2501672","DOIUrl":"https://doi.org/10.1080/07391102.2025.2501672","url":null,"abstract":"Brain cancer represents a highly aggressive malignant tumor with a challenging prognosis and limited treatment options. Employing advanced analytical methods, including Kinase Enrichment Analysis and Disease-Gene Network integration, the research identifies EGFR as a crucial therapeutic target for brain cancer. EGFR, a key player in cellular functions and elevated in various cancers, particularly brain cancer, is targeted using small molecule inhibitors like erlotinib and gefitinib. Despite promising results, challenges such as drug resistance and adverse effects necessitate exploration of alternative therapies. Natural compounds show significant potential for cancer with minimal associated toxicity. Thus, the natural compounds database was explored for EGFR kinase inhibitors. Utilizing molecular docking and dynamic simulation, our study identified five natural compounds-citicoline, silodosin, picroside I, canertinib, and tauroursodeoxycholic acid-as potential EGFR kinase inhibitors. Detailed exploration of their binding attributes, including pose, interacting residues, molecular interactions, dynamic behavior, and predicted binding energy, along with comparisons to the native inhibitor, underscored their potential. Notably, among the five natural compounds screened, canertinib is a known covalent inhibitor of EGFR kinase. However, its specific binding pose remains unexplored. Thus, to uncover the precise binding orientation, covalent docking simulation for canertinib was conducted. Additionally, it is noteworthy that all the five proposed compounds predicted to penetrate the blood-brain barrier, meeting the essential criteria for reaching brain. We anticipate that this study will provide valuable leads for experimental testing in the laboratory, advancing the prospects of brain cancer management.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-18"},"PeriodicalIF":2.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982274","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

Novel thiosemicarbazones of coumarin incorporated isatins: synthesis, structural characterization and antileishmanial activity. 香豆素中含有isatins的新型硫代氨基脲类化合物：合成、结构表征和抗利什曼原虫活性。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-06 DOI: 10.1080/07391102.2025.2498072

Saira Khatoon, Rabbia Asif, Saima Kalsoom, Aiman Aroosh, Arshad Islam, Syeda Sumayya Tariq, Zaheer Ul-Haq, Muhammad Moazzam Naseer

{"title":"Novel thiosemicarbazones of coumarin incorporated isatins: synthesis, structural characterization and antileishmanial activity.","authors":"Saira Khatoon, Rabbia Asif, Saima Kalsoom, Aiman Aroosh, Arshad Islam, Syeda Sumayya Tariq, Zaheer Ul-Haq, Muhammad Moazzam Naseer","doi":"10.1080/07391102.2025.2498072","DOIUrl":"https://doi.org/10.1080/07391102.2025.2498072","url":null,"abstract":"Leishmaniasis, a neglected tropical disease affecting 0.7 to 1.3 million people annually, has only a few toxic therapeutic options. This study describes the synthesis, structural characterization, in silico and in vitro assessment of novel thiosemicarbazones of coumarin incorporated isatins (6a-6m) as highly as potent and safe antileishmanial agents. Molecular docking was initially used to determine the binding of these compounds to the active cavity of the target protein (Leishmanolysin gp63) of Leishmania (L.) tropica. Among all the docked compounds, three 6d, 6f and 6l showed high binding affinities due to strong H-bonds and hydrophobic π-interactions. Importantly, the in vitro investigations of thirteen synthesized compounds for antileishmanial activity against L. tropica promastigotes and axenic amastigotes, complemented the docking results. The compound 6d was found to be the most active of the series at micromolar concentrations both against promastigotes (IC50 = 2.985 μmol/L) and axenic amastigotes (IC50 = 13.46 μmol/L) in comparison to the tarter emetic (IC50 = 12.56 μmol/L) and amphotericin B (IC50 = 1.826 μmol/L), respectively. Significantly, all active compounds are much less toxic as compared to the positive control (Triton X-100) and, tartar emetic (TA) and amphotericin B when screened for their toxicity against human erythrocytes. To gain further insight into the interaction dynamics of our target protein on binding with compound 6d, molecular dynamic simulation was performed for a course of 100 ns for both the apo-protein and the protein-ligand complex. The results revealed consistent structural stability for the protein-ligand complex, aligning with characteristics seen in the apo-proteins.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-13"},"PeriodicalIF":2.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009340","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

Computational study of diol camptothecin drug delivery process using MPEG-1-based nanosome structure: molecular dynamics approach. 基于mpeg -1纳米体结构的二醇喜树碱药物传递过程的计算研究：分子动力学方法。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-06 DOI: 10.1080/07391102.2025.2500686

Maziar Bahreini, Arezoo Ghaffari

{"title":"Computational study of diol camptothecin drug delivery process using MPEG-1-based nanosome structure: molecular dynamics approach.","authors":"Maziar Bahreini, Arezoo Ghaffari","doi":"10.1080/07391102.2025.2500686","DOIUrl":"https://doi.org/10.1080/07391102.2025.2500686","url":null,"abstract":"In recent years, the drug delivery process has become important for effective treatments of various diseases. However, drug carrier design is a complex procedure and many of designed structures do not perform well. Nanostructures are promising systems for effective drug delivery process. Between nanostructures, nanosomes are effective vesicles of spherical shape that can be created from different self-assembled nanosize components. It is expected the appropriate design of nanosome-based samples, introduced a suitable drug carrier for clinical applications. In current research, we introduced macrophage-expressed gene (MPEG-1) protein-based nanosome performance in diol camptothecin (CPT(OH)2) drug delivery process in aqueous environment for the first time. The molecular dynamics (MD) method implemented for this purpose by using dreiding force field. Our MD simulations were performed two main phases. In the first phase, defined samples equilibrated at initial condition (T0 = 300 K and P0 = 1 bar). Then, drug delivery performance of equilibrated samples was reported. Computational outputs predicted atomic stability of samples in standard condition. This performance is conducted from kinetic and potential energies convergence in equilibrium phase. Also, drug delivery process was detected after 0.12 ns in aqueous environment. Numerically, drug delivery ratio reached to 66%. Furthermore, zeta potential converged to -2.20 mV after 100 ns. From these outputs, we concluded MPEG-1-based nanosome can be used in actual cases for drug delivery in clinical applications.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-9"},"PeriodicalIF":2.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998060","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

Catechins anti-diabetic actions are mediated via multiple receptors, a mechanism deduced via molecular docking and dynamic simulations. 儿茶素的抗糖尿病作用是通过多种受体介导的，这一机制是通过分子对接和动态模拟推断出来的。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-06 DOI: 10.1080/07391102.2025.2499671

Muhanad Salih, Mosab Yahya Alnour, Tarig Omer Ahmed, Ahmed H Arbab, Bashir A Yousef

{"title":"Catechins anti-diabetic actions are mediated via multiple receptors, a mechanism deduced via molecular docking and dynamic simulations.","authors":"Muhanad Salih, Mosab Yahya Alnour, Tarig Omer Ahmed, Ahmed H Arbab, Bashir A Yousef","doi":"10.1080/07391102.2025.2499671","DOIUrl":"https://doi.org/10.1080/07391102.2025.2499671","url":null,"abstract":"Diabetes mellitus is a growing burden that affects a large proportion of the population worldwide, with long-term complications that cause a devastating effect on the function of various organs. The currently available treatments lack optimum therapeutic goals, increasing the need for new drug discovery. Catechins are natural flavonoids that demonstrate anti-diabetic effects; however, catechin's mechanism of action remains unclear. This study was aimed to unleash the molecular mechanism behind the catechin's effect on blood glucose levels. For that, we explored the capability of some catechins to bind and interact with glucagon-like peptide-1 receptor-1, pancreatic ATP-sensitive potassium channel, dipeptidyl peptidase-4, and sodium-glucose transporter-2, which is essential for euglycemia, using molecular docking screening and dynamic simulations. The results showed that all the tested catechins are potential sodium-glucose transporter-2 inhibitors, a mechanism revealed for the first time, and glucagon-like peptide-1 receptor-1 agonists with various affinities to these receptors. Moreover, among these compounds, (-)-Epigallocatechin 3-O-gallate, (-)-Gallocatechin 3-O-gallate demonstrated the ability to act as an ATP-sensitive potassium channel inhibitor, and dipeptidyl peptidase-4 inhibitor in addition to the previously mentioned mechanisms. The discovery introduces (-)-gallocatechin 3-O-gallate and (-)-Epigallocatechin 3-O-gallate as a hot subject for research, as the compounds require further optimization to initiate further pre-clinical and clinical studies.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-15"},"PeriodicalIF":2.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005705","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

Effects and molecular mechanisms of the combination of Andrographis paniculata and Anredera cordifolia as an insulin sensitizer: in vitro, network pharmacology, molecular docking, and dynamics studies. 穿心莲与凤梨联合作为胰岛素增敏剂的作用及分子机制：体外、网络药理学、分子对接及动力学研究。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-06 DOI: 10.1080/07391102.2025.2499224

Frangky Sangande, Sri Ningsih, Kurnia Agustini, Siska Andrina Kusumastuti, Nuralih Nuralih, Adam Arditya Fajriawan, Michael Chandra, Syofi Rosmalawati, Aiyi Asnawi, Krisyanti Budipramana

{"title":"Effects and molecular mechanisms of the combination of Andrographis paniculata and Anredera cordifolia as an insulin sensitizer: in vitro, network pharmacology, molecular docking, and dynamics studies.","authors":"Frangky Sangande, Sri Ningsih, Kurnia Agustini, Siska Andrina Kusumastuti, Nuralih Nuralih, Adam Arditya Fajriawan, Michael Chandra, Syofi Rosmalawati, Aiyi Asnawi, Krisyanti Budipramana","doi":"10.1080/07391102.2025.2499224","DOIUrl":"https://doi.org/10.1080/07391102.2025.2499224","url":null,"abstract":"Due to the complex mechanism of insulin resistance (IR), multi-component herbal medicines might be an alternative approach in the treatment of IR-related diseases, such as type 2 diabetes mellitus (T2DM). Andrographis paniculata (AP) and Anredera cordifolia (AC) have been reported to have anti-diabetic effects. However, their effect and mechanism of action in a mixed formula (FAPAC), especially as an insulin sensitizer have not been reported. Therefore, in vitro studies were performed to investigate the effect of FAPAC, and the molecular mechanisms were predicted by in silico studies through network pharmacology, molecular docking, and dynamics simulations. In vitro studies demonstrated that FAPAC at 2 µg/mL was comparable to metformin in increasing glucose uptake in IR-HepG2 cells. KEGG analysis revealed that IR was the top pathway and predicted that FAPAC acts as an insulin-sensitizing agent by inhibiting three main targets: IKBKB, PRKCD, and PTPN1. Consensus docking suggested 7-O-methyl wogonin, ninandrographolide, and 3-O-β-D-glucopyranosyl andrographolide as the potent inhibitors for IKBKB, PRKCD, and PTPN1, respectively. Furthermore, molecular dynamics confirmed that the potential compounds remained in the binding pocket throughout the simulation and had a good affinity toward their respective targets, comparable to native ligands.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-12"},"PeriodicalIF":2.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009965","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

Inhibition of erectile dysfunction-related enzymes by ginger (Zingiber officinale)-derived compounds: molecular docking and dynamics studies. 生姜（Zingiber officinale）衍生化合物对勃起功能障碍相关酶的抑制：分子对接和动力学研究

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-06 DOI: 10.1080/07391102.2025.2502153

Ayodeji Osmund Falade, Kayode Ezekiel Adewole, Gideon Ampoma Gyebi, Ibrahim M Ibrahim, Kolawole Ayodapo Olofinsan

{"title":"Inhibition of erectile dysfunction-related enzymes by ginger (Zingiber officinale)-derived compounds: molecular docking and dynamics studies.","authors":"Ayodeji Osmund Falade, Kayode Ezekiel Adewole, Gideon Ampoma Gyebi, Ibrahim M Ibrahim, Kolawole Ayodapo Olofinsan","doi":"10.1080/07391102.2025.2502153","DOIUrl":"https://doi.org/10.1080/07391102.2025.2502153","url":null,"abstract":"Erectile dysfunction (ED) is one of the common forms of sexual disorder that significantly impacts the psychosocial quality of life amongst male folks. Previous studies have evidenced the role of arginase-1 (Arg-1), angiotensin-I-converting enzyme (ACE), phosphodiesterase-5 (PDE-5) and acetylcholinesterase (AChE) in the progression of this pathology. In the current investigation, a library of compounds present in Zingiber officinale was screened to discover lead therapeutic agents for potential inhibitors of these metabolic enzymes. The compounds were subjected to molecular docking analysis with the various proteins' standard inhibitors. Subsequently, the thermodynamic stability of the protein-ligand complexes of two top-docked compounds with the highest binding affinities for each protein was studied further via molecular dynamics (MD) using the CHARMM-GUI website. Moreover, the Absorption-Distribution-Metabolism-Excretion-Toxicity (ADMET) pharmacological properties and drug-likeness of the top-docked 5 compounds from the plant were investigated with the SuperPred and the SwissADME web servers. From the compounds' library, diacetoxy-6-gingerdiol, 10-gingerdione, alloaromadendrene, valencene, and 6-gingerdiol showed the strongest inhibitory capacities with the amino acids present at the catalytic pocket of the selected proteins. Nonetheless, valencene and alloaromadendrene displayed better stability with the various protein complexes. Given that all these compounds were predicted to be non-toxic and have acceptable drug-likeness profiles, this investigation revealed their potential as a source of lead phytochemicals from regularly consumed food substances to mitigate the pathophysiology of erectile dysfunction. However, additional lab-based experiments are required before these phytochemicals can be developed into clinically approved commercially available drugs.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-21"},"PeriodicalIF":2.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016920","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

Computational structure-guided approach to simulate delamanid and pretomanid binding to mycobacterial F420 redox cycling proteins: identification of key determinants of resistance. 计算结构引导方法模拟delamanid和pretomanid与分枝杆菌F420氧化还原循环蛋白的结合：鉴定耐药性的关键决定因素。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-06 DOI: 10.1080/07391102.2025.2498621

Gourav Chakraborty, Mahima Sudhir Kolpe, I V Ambily Nath, Avlokita Tiwari, Praapti Jayaswal, Niladri Patra

{"title":"Computational structure-guided approach to simulate delamanid and pretomanid binding to mycobacterial F420 redox cycling proteins: identification of key determinants of resistance.","authors":"Gourav Chakraborty, Mahima Sudhir Kolpe, I V Ambily Nath, Avlokita Tiwari, Praapti Jayaswal, Niladri Patra","doi":"10.1080/07391102.2025.2498621","DOIUrl":"https://doi.org/10.1080/07391102.2025.2498621","url":null,"abstract":"The recently approved delamanid (DLM) and pretomanid (PTM) improved the existing options to treat multidrug-resistant tuberculosis (MDR-TB). However, the high spontaneous mutation rates in mycobacterial F420 genes ddn, fgd1, fbiA, fbiB, fbiC, and fbiD create a bottleneck to successful anti-TB treatments. Of known mutations, identifying the therapeutically relevant ones is a prerequisite for understanding the drug resistance mechanism. Here, we applied a multistep computational pipeline to rank the mutations in F420 genes associated with DLM/PTM resistance. The DLM-/PTM-resistant protein mutants were built and simulated their innate sensitivity towards the drugs. The molecular dynamics (MD) and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations quantified the effect of key mutations on drug union. The dynamic cross-correlated map (DCCM) and principal component analysis (PCA) showed a substantial link between the drug binding region and other sections in the mutants, hints to their potential role as an allosteric site. Also, the alterations induced conformationally unstable proteins with decreased DLM/PTM affinity. These investigations highlighted the DLM-tolerant G53D and Y65S and PTM-resilient Y133M (Ddn), L308P (FbiA), and C562W (FbiC) as candidate loss-of-function mutants of progressive research. The present results and interpretations could supply vital clues for protein engineering and drug development.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-21"},"PeriodicalIF":2.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984875","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

Computational investigations involving the structural, functional, and molecular dynamics analysis of bacterial laccase to unravel its role in lignin biodegradation. 计算研究涉及细菌漆酶的结构、功能和分子动力学分析，以揭示其在木质素生物降解中的作用。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-05 DOI: 10.1080/07391102.2025.2499216

Monalisa Mahuri, Manish Paul, Sumanta Kumar Sahu, Hrudayanath Thatoi

{"title":"Computational investigations involving the structural, functional, and molecular dynamics analysis of bacterial laccase to unravel its role in lignin biodegradation.","authors":"Monalisa Mahuri, Manish Paul, Sumanta Kumar Sahu, Hrudayanath Thatoi","doi":"10.1080/07391102.2025.2499216","DOIUrl":"https://doi.org/10.1080/07391102.2025.2499216","url":null,"abstract":"Laccase is an enzyme that belongs to the oxidoreductase family. Because of its delignifying characteristics, it has generated a lot attention as a pretreatment catalyst in the field of biofuel generation. In the present study, sequence and structural aspects of five bacterial laccase enzymes from L. xylanilyticum, P. australiense, O. urethralis, H. muridarum and J. saudimassiliensis have been retrieved from UniProtKB for sequence alignment, phylogenetic analysis using MEGA 7.0 and 3D structure prediction by homology modeling in Phyre2. The modeled laccase enzymes were docked with different ligands viz., ABTS, DMP and guaiacol using AutoDockVina for the relative binding energies between protein and ligand. The Dynamism between enzyme-substrates complex was determined by molecular dynamics simulation using GROMACS software. A comprehensive modeling study of bacterial laccase showed a structural fold, although there are significant divergences in the overall protein sequence, particularly in substrate-binding regions. Analyzing the relative binding energies between protein and ligand in the case of five modeled bacterial laccase enzyme complexes, it was evident that J. saudimassiliensis exhibited the highest binding affinities toward ABTS (-6.80 kcal/mol), DMP (-5.40 kcal/mol), and guaiacol (-5.10 kcal/mol). Molecular interaction investigations underscored the strong affinity of the bacterial laccase from J. saudimassiliensis for its substrates. The Molecular Dynamic simulations indicated that the DMP substrate-bound complex remained notably stable, with an average RMSD value consistently below 0.5 nm throughout a 100 ns timeframe. This in silico investigation might assist in advancing the understanding of bacterial laccase -mediated enzymatic catalysis and its pivotal role in lignin biodegradation.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-14"},"PeriodicalIF":2.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984932","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

Aldose reductase inhibition by the phenolic bioactive methylripariochromene A from Eupatorium spp. 紫茎泽兰酚类生物活性物甲基丙烯A对醛糖还原酶的抑制作用。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-05 DOI: 10.1080/07391102.2025.2498077

Rita Beltrán-Sánchez, Katia Lizbeth Alonso-Hurtado, Zurisaddai Hernández-Gallegos, Marcos Cajero-Juárez, Pedro Navarro-Santos, Rosa E Del Río-Torres, Mauro M Martínez-Pacheco

{"title":"Aldose reductase inhibition by the phenolic bioactive methylripariochromene A from Eupatorium spp.","authors":"Rita Beltrán-Sánchez, Katia Lizbeth Alonso-Hurtado, Zurisaddai Hernández-Gallegos, Marcos Cajero-Juárez, Pedro Navarro-Santos, Rosa E Del Río-Torres, Mauro M Martínez-Pacheco","doi":"10.1080/07391102.2025.2498077","DOIUrl":"https://doi.org/10.1080/07391102.2025.2498077","url":null,"abstract":"The lens cells of humans with chronic hyperglycemia show a progressive accumulation of sorbitol by aldose reductase catalysis that ends with cell lysis. Therefore, this work aims to explore metabolites in native plants that prevent cataracts through inhibition of the enzyme aldose reductase. The scrutiny was performed using bioinformatics, chemicals, enzymes, and cataract ex vivo prevention techniques. Eleven Eupatorium spp. were the natural resources explored. Five of them were selected to continue with the phytochemical scrutiny. Twelve pure phytometabolites were obtained with an inhibitory effect on the enzyme. Nine of them were subject to the accepted heuristic rules for drug-likeness. With this analysis, a possible active principle emerged a phenolic compound: methylripariochromene A. An apparent mixed catalytic mechanism carries out the inhibition of enzyme catalysis. Molecular docking and molecular dynamic simulations helped us understand their coupling in the active site of AR, finding an agreement between experimental and computational data. Methylripariochromene A prevented experimental cataract formation in rabbit lens cultured ex vivo.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-15"},"PeriodicalIF":2.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026315","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

One-pot four-component synthesis of some novel hydrazone-Schiff bases of polyhydroquinoline as potent tyrosinase inhibitors: in vitro, molecular docking and simulations approaches. 新型聚对苯二酚腙希夫碱作为酪氨酸酶抑制剂的一锅四组分合成：体外、分子对接和模拟方法。

IF 2.7 3区生物学

Journal of Biomolecular Structure & Dynamics Pub Date : 2025-05-05 DOI: 10.1080/07391102.2025.2497458

Sajjad Ur Rahman, Muhammad Naveed Umar, Aftab Alam, Zainab, Ahmed A Elhenawy, Mumtaz Ali, Saeed Ullah, Sobia Ahsan Halim, Ajmal Khan, Abdul Latif, Ahmad Al-Harrasi, Manzoor Ahmad

{"title":"One-pot four-component synthesis of some novel hydrazone-Schiff bases of polyhydroquinoline as potent tyrosinase inhibitors: in vitro, molecular docking and simulations approaches.","authors":"Sajjad Ur Rahman, Muhammad Naveed Umar, Aftab Alam, Zainab, Ahmed A Elhenawy, Mumtaz Ali, Saeed Ullah, Sobia Ahsan Halim, Ajmal Khan, Abdul Latif, Ahmad Al-Harrasi, Manzoor Ahmad","doi":"10.1080/07391102.2025.2497458","DOIUrl":"https://doi.org/10.1080/07391102.2025.2497458","url":null,"abstract":"Seventeen novel polyhydroquinoline (1) based Schiff bases (4-20) were synthesized in excellent yields through Hantzsch reaction, characterized by means of spectroscopic techniques and finally screened for their in vitro tyrosinase inhibitory potential. Among the series, five compounds 12 (IC50 = 8.93 ± 0.27 µM), 8 (IC50 = 16.64 ± 0.32 µM), 5 (IC50 = 17.74 ± 0.34 µM), 4 (IC50 = 18.46 ± 0.37 µM) and 18 (IC50 = 18.64 ± 0.39 µM) were found potent inhibitors of tyrosinase enzyme by comparing with kojic acid (IC50 = 18.30 ± 0.41 µM). Likewise, eight derivatives 7, 15, 9, 6, 10, 13, 14 and 11 ascribed significant activity having IC50 values of 20.72 ± 0.45, 22.53 ± 0.61, 24.17 ± 0.40, 25.72 ± 0.60, 26.43 ± 0.39, 27.90 ± 0.53, 28.37 ± 0.59 and 29.15 ± 0.64 µM respectively, while the remaining four hydrazone-Schiff bases 19, 20, 17 and 16 exhibited good to less inhibitory potential in the range of IC50 values from 31.58 ± 0.67 to 63.69 ± 1.30 µM. Docking studies indicate excellent binding of the hydrazide moiety of the most active compound 12 with the active site residues of tyrosinase. The molecular dynamic simulation indicates that the most potent inhibitors 12 and 8 showed that root mean square deviation profile of the complexes stabilized at low nanoseconds, indicating stable conformations. These compounds did not induce significant structural changes in the protein.","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-16"},"PeriodicalIF":2.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986633","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}

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