Journal of Biomolecular Structure & Dynamics最新文献

{"title":"Exploring the binding interactions of bicalutamide with bovine serum albumin: spectroscopic techniques and molecular modeling studies.","authors":"Girish Ariga, Laxmi Jattinagoudar, Sharanappa Nandibewoor, Shivamurthi Chimatadar","doi":"10.1080/07391102.2025.2475226","DOIUrl":"https://doi.org/10.1080/07391102.2025.2475226","url":null,"abstract":"<p><p>The current study employed a variety of spectroscopic methods and molecular modeling to thoroughly look at, under physiological settings, the interaction between bicalutamide (BIC) and bovine serum albumin (BSA). According to our study, the BSA-BIC system's static quenching procedure is supported by the Stern-Volmer quenching constants. The binding constant dropped with temperature, implying that the BSA-BIC complex was weakened. The BSA absorption spectra shifted to a lower wavelength area (from 278 to 272 nm) upon the addition of BIC. The distance (r) between the acceptor and donor in the complex of BIC-BSA and circular dichroism (CD) spectra show the molecular exchanges between BIC and BSA. This study is essential for understanding the therapeutic approach to cancer management through drug distribution and pharmacological effectiveness.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-10"},"PeriodicalIF":2.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585858","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":"A type of phenolic compound, hydroxyacetophenone: tyrosinase inhibition mechanism evaluation by application of biochemical assay and computational molecular dynamics.","authors":"Jie-Hao Xu, Wei Wang, Jinhyuk Lee, Yong-Doo Park","doi":"10.1080/07391102.2025.2477143","DOIUrl":"10.1080/07391102.2025.2477143","url":null,"abstract":"<p><p>Screening and developing tyrosinase inhibitors with novel structures are notable to receive attention in the field of skin pigmentation research due to their application in hyperpigmentation control. Hydroxyacetophenone is a natural antioxidant found in the <i>Picea abies</i> (Norwegian spruce) needles and is widely used in the cosmetic industry as an antioxidant ingredient. In this study, integrations of virtual molecular dynamics (MD) simulations and biochemical inhibition kinetics were conducted to validate the inhibitory function of hydroxyacetophenone on tyrosinase. Docking and 100 ns MD simulations revealed that hydroxyacetophenone docks onto the active site of tyrosinase, and the eight key binding residues (HIS61, CYS83, HIS85, PHE90, HIS259, ASN260, HIS263, and VAL283) were identified through distance-time profile analysis. Subsequently, serial comparisons of inhibition kinetics including a spectrometry study were conducted to validate the simulation results. Hydroxyacetophenone displayed a typical reversible and competitive type of inhibition. Measurements of the fluorescence spectrum showed hydroxyacetophenone modulated the hydrophobic condition of active site pocket in tyrosinase. Taken together, one phenolic hydroxyl group of hydroxyacetophenone exerts a hub function in tyrosinase catalytic retardation <i>via</i> ligand binding. This study illustrates the new utility of hydroxyacetophenone function in the whitening agent-related industry as a tyrosinase inhibitor.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-13"},"PeriodicalIF":2.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582289","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 MERTK inhibitor binding mechanisms: insights from adaptive steered molecular dynamics and free energy calculation.","authors":"Yanmin Zhang, Yi Hua, Lingxi Gu, Wenhao Ji, Kairan Cui, Haoxuan Luo, Chao Xu, Haichun Liu, Xian Wei, Yadong Chen","doi":"10.1080/07391102.2025.2475227","DOIUrl":"10.1080/07391102.2025.2475227","url":null,"abstract":"<p><p>MERTK, a promising drug target for the treatment of human leukemia and solid tumors, and the development of its small molecule inhibitors holds significant clinical potential. However, the underlying reasons for the varying activities among these inhibitors and the specifics of their binding mechanism have not been systematically investigated. By combining conventional molecular dynamics simulations, adaptive steered molecular dynamics simulations and binding free energy calculations based on molecular mechanics Poisson-Boltzmann surface area, the interaction modes of four MERTK inhibitors and dissociation behavior are discussed in detail. The results reveal additional critical amino acids, beyond the well-known hot spot residues in the kinase hinge region, that play a pivotal role in inhibitor binding. Our findings further indicate that the binding of MERTK to its inhibitors relies not only on crucial hydrogen bonding interactions but also benefits from non-polar interactions. In addition, the analysis of hydrogen bonding within kinetic trajectories and potential of mean force explained the differences in activity between different inhibitors, providing insights for the design and optimization of subsequent MERTK-targeted small molecule inhibitors.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-16"},"PeriodicalIF":2.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582305","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":"Modeling substrate efflux in human P-glycoprotein at the atomic level.","authors":"Yingjie Gao, Yang Tang, Caiyan Wei, Yongzhen Yu, Jiming Xie, Yaling Li, Siping Wei, Juan Xing, Xianchao Pan","doi":"10.1080/07391102.2025.2474048","DOIUrl":"https://doi.org/10.1080/07391102.2025.2474048","url":null,"abstract":"<p><p>Human P-glycoprotein (hP-gp) is an ATP-binding cassette (ABC) exporter that actively extrudes a wide range of xenobiotics from the cell, thus limiting drug delivery and contributing to multidrug resistance (MDR) in cancers. Recent structural studies have provided insights into how hP-gp binds diverse compounds, but how they are translocated through the membrane remains poorly understood at the atomic level. In this work, we used steered molecular dynamics (SMD) simulations to investigate the molecular mechanism of how hP-gp expels structurally different compounds and which molecular features favor this efflux step. The potential of mean force (PMF) and structural dynamics analysis showed that the bending of TM1 favored the translocation of vincristine, whereas the high flexibility of tariquidar made it easier to pass through the narrow exit tunnel, suggesting a wide opening of the extracellular gate is not required for the efflux of both compounds. Moreover, an alternating-site hydrolysis mechanism may be shared in which ATP bound in the second nucleotide-binding site was preferentially hydrolyzed to provide chemical energy for the flexible-to-rigid transition of TM10. A conserved salt bridge between the fourth intracellular loop and the flexible X-loop was formed in response to ATP binding, which may participate in the interdomain communication. Furthermore, the SMD trajectories revealed two translocation pathways in the hP-gp cavity, one of which is preferentially but non-exclusively taken by a set of compounds. These findings provide deep insights into the efflux mechanism of hP-gp and will help rational design and development of more selective and effective inhibitors.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-13"},"PeriodicalIF":2.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573010","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":"A novel water-soluble dinuclear Pd(II) complex having 4,4'- bipyridine and diethylenetriamine ligands and its interaction with DNA and BSA.","authors":"Narjes Alisufi, Effat Dehghanian, Hassan Mansouri-Torshizi, Fatemeh Mohammadi, Leila Dehghanian","doi":"10.1080/07391102.2025.2475386","DOIUrl":"https://doi.org/10.1080/07391102.2025.2475386","url":null,"abstract":"<p><p>A novel dinuclear palladium(II) complex <i>i.e.,</i> [{Pd(dien)}₂(µ-4,4'-bpy)]Cl₄, (dien = diethylenetriamine and bpy = bipyridine), has been synthesized and characterized by means of conductivity measurement, elemental analysis, FT-IR, 1D ¹H NMR, 2D ¹H NMR and ¹³C NMR. Binding characteristics of this complex to DNA and BSA was investigated by electronic absorption, fluorescence, electrophoresis, energy transfer, circular dichroism and cyclic voltammetry which revealed that van der Waals and hydrogen bonds are the main binding forces for the di-Pd(II) complex interaction with the mentioned biomacromolecules. The cytotoxicity assay of the di-Pd(II) complex has been performed on human acute lymphoblastic leukemia (MOLT-4) cell line. Finally, to identify DNA/BSA binding site for the metal complex, theoretical investigations were conducted utilizing molecular docking.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-16"},"PeriodicalIF":2.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585856","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":"Computer-aided drug design approach for alkaloids isolated from <i>Stephania glandulifera</i> Miers as potential acetylcholinesterase inhibitors.","authors":"Jhalnath Dhungel, Sajan L Shyaula, Mishal Faizan, Rajitha Kalum Rathnayaka, Mohit Agrawal","doi":"10.1080/07391102.2025.2474054","DOIUrl":"https://doi.org/10.1080/07391102.2025.2474054","url":null,"abstract":"<p><p>Considering the medicinal importance of alkaloids from <i>Stephania glandulifera</i> Miers, five major compounds (stepharine, stepharanine, stepholidine, palmatine and tetrahydropalmatine) from the plant were analyzed for their acetylcholinesterase activity using molecular docking, molecular dynamics simulations and <i>in silico</i> pharmacokinetics. As acetylcholinesterase has been significantly studied for their role in Alzheimer's disease, the enzyme from <i>Torpedo californica</i> (PDB ID: 1QTI) was taken as a receptor protein. AutoDock Vina was used to study the docking affinities during the initial screening of compounds where, stepharine showed promising binding energy (-10.3 kcal/mol) forming crucial interactions with active site residues (His 440, Tyr 121, and Trp 84). Molecular dynamics simulations were performed for 200 ns to analyze the stability of the docked complex. The study of trajectories obtained after simulation showed stepharine with a strong binding affinity and stability with AChE. Moreover, drug likeness and ADMET analysis conducted via Swiss ADME and pKCSM affirmed stepharine's favorable pharmacological properties. Overall, this research highlights stepharine as a potent acetylcholinesterase inhibitor which could be further developed as potential drug against Alzheimer's disease.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-14"},"PeriodicalIF":2.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575637","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 insight into cross-interaction between amyloid β isoforms and its effect on aggregation pathways.","authors":"Li Wang, Sanghwan Park, Jae Hong Choi, Chang Young Lee, Kilho Eom, Taeyun Kwon","doi":"10.1080/07391102.2025.2475221","DOIUrl":"https://doi.org/10.1080/07391102.2025.2475221","url":null,"abstract":"<p><p>The self-aggregation of amyloid β (Aβ) proteins has played a crucial role in the pathogenesis of Alzheimer's diseases. Despite previous studies on the aggregation process of Aβ proteins, little is known about how the cross-interaction between Aβ isoforms affects the aggregation pathways and the resulting structures of Aβ aggregates. Here, we study the cross-interaction between Aβ40 and Aβ42 during their aggregation process by measuring the aggregation kinetics and the structures of Aβ aggregates under varied concentrations of Aβ isoform proteins in their mixture. We found that the mixture of Aβ40 and Aβ42 monomers results in the concentration-dependent aggregation process leading to different aggregate structures in such a way that the different concentrations of Aβ40 and Aβ42 induce the different structural types of aggregates such as different sized oligomers or fibrils with their different morphologies and flexibilities. Moreover, we investigate the effect of Aβ40 (or Aβ42) oligomer and fibril seeds in the aggregation pathway of Aβ42 (or Aβ40). We show that the oligomer (or fibril) seed affects not only the aggregation kinetics but also the structures of Aβ aggregates. Our study sheds light on the cross-interaction between Aβ isoforms at primary nucleation level and its role in the aggregation pathways.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-11"},"PeriodicalIF":2.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585859","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":"<i>In silico</i> identification of Corylifol C as a potential natural inhibitor of BfrB-Bfd interaction in <i>Pseudomonas aeruginosa</i>.","authors":"Ananya Anurag Anand, Sarfraz Anwar, Amaresh Kumar Sahoo, Sintu Kumar Samanta","doi":"10.1080/07391102.2025.2472171","DOIUrl":"https://doi.org/10.1080/07391102.2025.2472171","url":null,"abstract":"<p><p>Looking for potential alternatives to conventional antibiofilm agents has become a significant concern in treating drug-resistant <i>Pseudomonas aeruginosa</i> infections. In this study, we have tried to identify a potential natural antibacterial and antibiofilm compound against <i>P. aeruginosa</i>. Iron plays a crucial role in the virulence of <i>P. aeruginosa</i> biofilms. It is required for biofilm formation as well as for the production of the key virulence factors. The acquisition and utilization of iron within biofilms contribute to their resilience and ability to cause chronic infections. The interaction between Bacterioferritin (BfrB) and Ferredoxin (Bfd) in <i>P. aeruginosa</i> plays a crucial role in the mobilization of iron. Bfd facilitates the release of iron stored in BfrB, leading to the transfer of Fe²⁺ into the cytosol for bacterial metabolism. This process is vital for maintaining iron homeostasis and supporting various cellular processes. In our study, we have explored the potential of 27 antibacterial flavonoid compounds as ligands to inhibit the interaction between Bacterioferritin (BfrB) and Ferredoxin (Bfd). Through a series of computational analyses, including docking, MMGBSA, ADME, and MD simulation, we have identified Corylifol C as one of the most effective drug candidates capable of blocking the Bacterioferritin-Ferredoxin interaction. These findings suggest that Corylifol C may be used as a potential inhibitor to disrupt iron mobilization and may serve as a promising natural therapeutic agent. The study includes two reference compounds with known potential to block the Bacterioferritin-Ferredoxin interaction. Further wet-laboratory validation can help in establishing the antibacterial and antibiofilm properties of Corylifol C.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-15"},"PeriodicalIF":2.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567238","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":"Combined <i>in vitro</i> and <i>in silico</i> approach to define alangimarckine from <i>Thunbergia mysorensis</i> leaves as a potential inhibitor of α-glucosidase.","authors":"N R Kokila, B Mahesh, Ramith Ramu, S G Divakara, K Mruthunjaya, Neera Raghav, Thippeswamy Boreddy Shivanandappa","doi":"10.1080/07391102.2025.2472396","DOIUrl":"https://doi.org/10.1080/07391102.2025.2472396","url":null,"abstract":"<p><p>The current work investigated biocomputational methodologies for α-glucosidase inhibition to examine the antidiabetic potential of methanolic extract of <i>T. mysorensis</i> leaves (MeL). MeL intensely impeded yeast-glucosidase, which is vital for treating postprandial hyperglycemia (IC₅₀ = 5.76 ± 0.10 μg/mL) in comparison to an acarbose control (IC₅₀ = 7.98 ± 0.23 μg/mL). The MeL is affected by phytochemical profiling employing LC-MS, GC-MS, and HPLC analysis to determine the bioactive components responsible for the antidiabetic activity. The specified phytocompounds were employed <i>in silico</i> research following the bioactive profiling, where they were docked into the inhibitor binding site of α-glucosidase. Molecular docking simulations, molecular dynamics simulations, and binding free energy inquiries were utilized <i>in silico</i> research to clarify the mechanism by which <i>T. mysorensis</i> phytocompounds block α-glucosidase. Alangimarckine is a glucocorticoid that is used to treat nasal symptoms. Alangimarckine inhibited the target enzyme with greater binding efficiency (-9.7 kcal/mol) than the acarbose control (-8.6 kcal/mol) during molecular docking. Concerning molecular dynamics simulation studies, Alangimarckine-α-glucosidase complex was found to be stable inside the inhibitor binding site of the protein, compared to the acarbose -α-glucosidase complex. Additionally, alangimarckine inhibited α-glucosidase at IC₅₀ = 5.32 ± 0.19 μg/mL during <i>in vitro</i> inhibition of α-glucosidase, which was efficient in comparison to both MeL and acarbose. Therefore, our research suggests that alangimarckine and MeL from <i>T. mysorensis</i> may function as potent antidiabetic medications. Alangimarckine could be used in <i>in vivo</i> and clinical investigations to specify its antidiabetic properties that target α-glucosidase inhibition.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-20"},"PeriodicalIF":2.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567259","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":"Insight into virus movement mechanism using <i>in silico</i> approaches by employing SeMV as a model system.","authors":"Jyotilipsa Mohanty, Lukkani Laxman Kumar, Ayaluru Murali","doi":"10.1080/07391102.2025.2474063","DOIUrl":"https://doi.org/10.1080/07391102.2025.2474063","url":null,"abstract":"<p><p>Viral infections in plants are a big threat to agriculture and the economy. Though the viral infection mechanism is well documented, the cell-to-cell trafficking of the virus is poorly understood. The plant virus is known to encode movement protein (MP) for trafficking the virus from an infected cell to a healthy cell. The movement protein is known to increase plant cells' size exclusion limit (SEL) of plasmodesmata (PD). However, the exact mechanism of the viral trafficking remained unclear. In this study, we proposed a possible mechanism of viral trafficking by using <i>Sesbania mosaic virus</i> (SeMV) as a model system. The movement protein and RNA-dependent RNA polymerase (RdRp) of SeMV were modeled using the <i>ab initio</i> method. It is also known that MP binds with VPg in the movement process and RdRp requires P10 for replication. The models of VPg and P10 were extracted from the structure of polyprotein 2a. The complexes MP-VPg and RdRp-P10 were built with the help of molecular docking and were subjected to molecular dynamic simulation to get stable complexes. The trafficking complex (MP+VPg + RdRp + P10) was obtained by performing the molecular docking of these two complexes. Through MDS, the stability of the trafficking complex was confirmed. For the first time, a trafficking complex was proposed to understand its role in navigation of the viral complex through the host's plasmodesmata.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1-13"},"PeriodicalIF":2.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573008","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}