Biophysical chemistry最新文献

{"title":"Effect of pyrimethanil on aβ42 aggregation mechanisms revealed at single entity level and molecular dynamic simulations","authors":"Nathan Meyer ,&nbsp;Nicolas Arroyo ,&nbsp;Lois Roustan ,&nbsp;Jean-Marc Janot ,&nbsp;Véronique Perrier ,&nbsp;Joan Torrent ,&nbsp;Fabien Picaud ,&nbsp;Sebastien Balme","doi":"10.1016/j.bpc.2025.107471","DOIUrl":"10.1016/j.bpc.2025.107471","url":null,"abstract":"<div><div>This study investigated the impact of pyrimethanil, a fungicide, on the aggregation of amyloid-β 42 (aβ42) peptides in vitro. The findings demonstrated that pyrimethanil accelerated aβ42 aggregation kinetics, as evidenced by thioflavin T (ThT) fluorescence assays in both tube and microplate experiments. A combination of single molecule techniques and molecular dynamics simulations is used to elucidate the complex effects of pyrimethanil on aβ42 aggregation mechanism. Nanopore experiments indicated that pyrimethanil promoted the formation of small oligomers (6-13.5 nm) during the lag phase, which were not detected under control conditions. Confocal fluorescence spectroscopy revealed that pyrimethanil induced the formation of larger β-sheet structured aggregates. In the presence of preformed seeds, pyrimethanil exhibited a dual role by fragmenting existing fibrils into smaller species and enhancing aggregation, likely through combined effects with the newly formed smaller seeds. Molecular dynamics simulations confirmed that pyrimethanil has a higher affinity for fibrils than monomers and weakens monomer-fibril interactions. Overall, this study elucidates the complex effects of pyrimethanil on aβ42 aggregation, involving promotion of primary nucleation, fibril fragmentation, and modulation of monomer-fibril interactions. These findings provide important mechanistic insights into how environmental factors like pesticides may influence amyloid aggregation processes relevant to Alzheimer's disease.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"325 ","pages":"Article 107471"},"PeriodicalIF":3.3,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212245","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":"Influence of local ordering in the permeation of Temozolomide through the brain plasmatic membrane","authors":"Yanhong Ge ,&nbsp;Huixia Lu ,&nbsp;Jordi Martí","doi":"10.1016/j.bpc.2025.107457","DOIUrl":"10.1016/j.bpc.2025.107457","url":null,"abstract":"<div><div>Temozolomide, a small-molecule drug, is primarily used to treat glioblastoma, a tumor that attacks both the spinal cord and brain. Understanding how Temozolomide interacts with different lipids within the brain cell membrane at the atomic level can help elucidate its ability to permeate through cell membranes. In this study, we constructed a simplified brain plasma membrane model to explore the microscopic structure and dynamics of Temozolomide using all-atom microsecond-scale molecular dynamics simulations. Temozolomide is typically found in the solvent-aqueous fluid surrounding the brain membrane, but it can access the membrane interface regularly and eventually bind to lipids of the choline and cerebroside classes. To investigate the free energy barriers of Temozolomide related to its crossing of brain-like plasma membranes, we employed adaptive biasing force methods. These simulations revealed that the free energy barriers ranged between 28 and 50 kcal/mol at temperatures between 310 K and 323 K. Our findings suggest that Temozolomide cannot cross the membrane by pure diffusion at normal human body temperature, but that rising the temperature significantly increases the probability of barrier crossing. This is primarily due to the crucial role played by cholesterol and lipids of the cerebroside class. These results can be used to optimise the molecular design of Temozolomide and develop new analogs with improved pharmacokinetic properties.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"324 ","pages":"Article 107457"},"PeriodicalIF":3.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169142","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":"Lysozyme thermal stability in the presence of cyclodextrins at different pH values","authors":"A. Jessica Díaz-Salazar ,&nbsp;Daniel Ondo","doi":"10.1016/j.bpc.2025.107469","DOIUrl":"10.1016/j.bpc.2025.107469","url":null,"abstract":"<div><div>In the present study, the primary action of native cyclodextrins (CDs) on lysozyme protein as binding ligand and secondary as aggregation inhibitor were probed. Thermally induced denaturation using differential scanning calorimetry (DSC) was measured in the presence of native <span><math><mi>α</mi></math></span>-, <span><math><mi>β</mi></math></span>- and <span><math><mi>γ</mi></math></span>-CDs. The denaturation process in CD absence was reversible to 60–80 % at pH<span><math><mo>≤</mo></math></span>6 with maximum <span><math><msub><mi>T</mi><mi>m</mi></msub></math></span> at pH<span><math><mo>=</mo></math></span>4. Denaturation in the presence of native <span><math><mi>α</mi></math></span>-CD at pH from 2 to 10, at the least stable and partially reversible conditions in presence of <span><math><mi>β</mi></math></span>-CD and <span><math><mi>γ</mi></math></span>-CDs at single pH 2 only, was measured. The protein thermal stability decreases in the presence of CDs, with the most evident for <span><math><mi>β</mi></math></span>-CD, followed by <span><math><mi>α</mi></math></span>-CD and almost no effect for <span><math><mi>γ</mi></math></span>-CD. The reversibility in the presence of <span><math><mi>α</mi></math></span>-CD was similar to that in its absence. The best protection performance against heat-induced denaturation was found at pH 2 for <span><math><mi>β</mi></math></span>-CD. The heat capacity data for <span><math><mi>α</mi></math></span>-CD at acidic pH were fitted by the protein-ligand binding model in the whole temperature and ligand concentration ranges studied. The decrease in thermal stability for <span><math><mi>α</mi></math></span>-CD at all pH, <span><math><mi>β</mi></math></span>- and <span><math><mi>γ</mi></math></span>-CD at pH 2 were fitted linearly as a function of ligand concentration. The CD-to-lysozyme binding parameters obtained in this work and from the literature for other CDs are briefly discussed using the concept of cyclodextrin cavity size, charge distribution, solvent accessible surface area and amino acid hydrophobicity.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"324 ","pages":"Article 107469"},"PeriodicalIF":3.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169143","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":"Identification of potential Abl kinase inhibitors using virtual screening and free energy calculations for the treatment of chronic myeloid leukemia","authors":"Beom Soo Kim ,&nbsp;Wookyung Yu","doi":"10.1016/j.bpc.2025.107470","DOIUrl":"10.1016/j.bpc.2025.107470","url":null,"abstract":"<div><div>Abl kinase, particularly the Bcr-Abl fusion protein, is a critical driver of chronic myeloid leukemia (CML) and remain significant therapeutic target in hematologic malignancies. Although first-generation tyrosine kinase inhibitors (TKIs) such as Imatinib have revolutionized CML treatment, resistance due to kinase domain mutations (<em>e.g.</em>, T315I gatekeeper mutation) and side effects highlight needs for another candidate inhibitors. In this study, we employed a combined virtual screening strategy to discover novel Abl kinase inhibitors from an extensive chemical database (∼670 million compounds). Initially, shape-based similarity (USR/USRCAT) and electrostatic potential filters were used to refine the candidate compounds, followed by structure-based molecular docking against the Abl kinase domain. Top-ranked candidates were evaluated using molecular dynamics (MD) simulations and binding free energy calculations, such as MM/GBSA and free energy perturbation (FEP), to confirm stability and binding affinity. Five candidate compounds emerged with binding energies comparable to or higher than known Abl kinase inhibitors, including Imatinib and Bafetinib. Finally, based on these calculations, we selected two compounds as candidates as Abl tyrosine kinase inhibitors. Overall, the results showed the effectiveness of combining ligand-based and structure-based drug design strategies to identify new Abl kinase inhibitor leads for improved the CML therapy.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"324 ","pages":"Article 107470"},"PeriodicalIF":3.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144116176","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":"Integrative approaches to network pharmacology studies in wound healing and bone fracture recovery: A comprehensive review","authors":"Rizwan Ahamed Najimudeen ,&nbsp;Catherin Amaldoss ,&nbsp;Aarthi Raghu ,&nbsp;Alex Anand Daniel ,&nbsp;Dilip Kumar Shanmugam ,&nbsp;Prakash Pandurangan ,&nbsp;Subbaiya Ramasamy","doi":"10.1016/j.bpc.2025.107458","DOIUrl":"10.1016/j.bpc.2025.107458","url":null,"abstract":"<div><div>This review provides a comprehensive exploration of the intricate processes involved in wound healing and bone fracture recovery, delving into the phases and cellular activities that underlie these critical physiological events. The integration of network pharmacology and traditional medicine approaches in the context of wound healing and bone fracture is thoroughly examined, highlighting the potential synergies between modern scientific methodologies and age-old remedies. The Research methodology for network pharmacology studies is meticulously outlined, encompassing data mining, target identification, network construction and analysis, and validation techniques. Various Bioinformatics Databases and tools implied in the network pharmacology are tabulated. The genes responsible for wound healing and bone fracture are also tabulated. By synthesizing knowledge from diverse fields, this review offers valuable insights for advancing therapeutic interventions in wound healing and bone fracture management through network pharmacology study.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"324 ","pages":"Article 107458"},"PeriodicalIF":3.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144185671","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":"Lyophilized nasal swabs for COVID-19 detection by ATR-FTIR spectroscopy: Machine learning-based approach","authors":"Zubia Shahid ,&nbsp;Khulla Naseer ,&nbsp;Irshad Hussain ,&nbsp;Javaria Qazi","doi":"10.1016/j.bpc.2025.107459","DOIUrl":"10.1016/j.bpc.2025.107459","url":null,"abstract":"<div><div>The COVID-19 pandemic continues to pose challenges for global health. The disease burden and diagnostic pressure has forced scientists to explore alternate diagnostic tools beyond the standard PCR testing. One such promising tool is the use of spectroscopy-based diagnostics. The objective of this study is to assess the potential of ATR-FTIR spectroscopy, applied to lyophilized nasal swab samples to discriminate between healthy and infected COVID-19 patients. Equal number (55 each) of positive and negative freeze-dried nasal swab samples were analyzed. After pre-processing, average mean spectra (600–4000 cm⁻¹) showed significant variations between healthy and infected sample types. Clear spectral variations were recorded at 17 locations, of which, 13 peaks were observed in COVID-19 spectra while 4 peaks were observed in negative sample spectra. Statistical discrimination was done using principal component analysis (PCA), linear discriminant analysis (LDA) and support vector machine (SVM). The first two principal components (PCs) showed a combined variance of 76 %. Classification accuracy of 100 % were observed in the LDA graph using Quadratic kernel. Similarly, SVM model with both internal validation and external validation confirmed the robustness with a 100 % classification accuracy. These results show that lyophilized nasal swab samples are the ideal sample choice for FTIR-based analysis of COVID-19. This sample preparation method coupled with spectroscopy can serve as a robust and accessible diagnostic tool for post-covid testing.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"324 ","pages":"Article 107459"},"PeriodicalIF":3.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070116","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":"Deterministic error propagation in ITC: Revealing multi-fold errors in Kd values under standard conditions","authors":"Tong Ye Wang ,&nbsp;Sergey N. Krylov","doi":"10.1016/j.bpc.2025.107455","DOIUrl":"10.1016/j.bpc.2025.107455","url":null,"abstract":"<div><div>Accurate determination of the equilibrium dissociation constant (<em>K</em>_d) is essential in fields such as drug discovery and molecular diagnostics, where a rigorous understanding of molecular interactions drives critical decisions. Among established techniques, isothermal titration calorimetry (ITC) is highly valued for its ability to directly capture binding thermodynamics without the need for labeling or immobilization. However, while ITC is often praised for its precision, potential inaccuracies due to the systematic errors in experimental variables (analyte concentrations and measured heat) are frequently overlooked. One key reason for this oversight is the lack of a deterministic framework that explicitly demonstrates how ITC-derived <em>K</em>_d values can be affected by these errors. To address this gap, we derived a closed-form mathematical model for error propagation in ITC-based <em>K</em>_d determination, quantifying the impact of inaccuracies in analyte concentrations and measured heat on the resulting <em>K</em>_d. This framework provides a robust foundation for understanding and predicting the influence of these systematic errors on <em>K</em>_d accuracy. Using this solution, we demonstrate that even within the conventionally recommended <em>c</em>-value range of 10–100, expected systematic errors in concentrations and heat can potentially lead to significant multi-fold deviations in <em>K</em>_d. These findings underscore the need for quantitative accuracy assessments in ITC experiments and highlight the importance of developing practical tools to support such evaluations.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"323 ","pages":"Article 107455"},"PeriodicalIF":3.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931593","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":"Effects of perturbation of the hydrophobic coiled-coil core on the thermal transition process of α-helical self-assembling peptides with α-β conformational transition capability","authors":"Minami Kurokawa ,&nbsp;Shota Nakagawa ,&nbsp;Atsuo Tamura","doi":"10.1016/j.bpc.2025.107456","DOIUrl":"10.1016/j.bpc.2025.107456","url":null,"abstract":"<div><div>We designed a 29-residue peptide (CCP1) with helical nanofiber-forming ability, in which the interface of the coiled-coil motif consists only of hydrophobic residues, and peptides with histidine residues substituted in the hydrophobic core (CCP2 and CCP3), and analyzed the effects of perturbations caused by the substitutions on the intermolecular association and conformational transitions. Based on the results of atomic force microscopy and circular dichroism measurements, it was found that CCP1 and CCP2 form α-helical fibers under pH 4, while CCP3 adopts the α-helix structure but lacks the association ability. Furthermore, the heating processes of CCP1 and CCP2 were followed by using spectroscopic, thermal, and morphological techniques, and it was observed that CCP1 undergoes an irreversible structural transition from α-helical to β-sheet fibers with a high degree of cooperativity, while a more gradual or non-cooperative structural transition was observed in CCP2. These results indicate that the introduction of histidine residues in the hydrophobic core significantly affects the intermolecular interactions and the rate of structural transition, providing a new design principle for the development of functional nanomaterials with biocompatibility.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"323 ","pages":"Article 107456"},"PeriodicalIF":3.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935905","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":"Two-step upconversion-driven PDT/CDT cooperative phototherapeutic platform based on surface magnetic field modulation","authors":"Changqiu Ma ,&nbsp;Anqi Han ,&nbsp;Daheng Jiang ,&nbsp;Qiuyan Wang ,&nbsp;Linghui Zeng ,&nbsp;Lixin Zhu ,&nbsp;Mingya Yang ,&nbsp;Xiaoliang Xu","doi":"10.1016/j.bpc.2025.107454","DOIUrl":"10.1016/j.bpc.2025.107454","url":null,"abstract":"<div><div>Photodynamic therapy utilizes photosensitizer to generate reactive oxygen species (ROS) under irradiation of light for anticancer. However, due to the strong absorption of visible light by tissues and organs, photodynamic therapy meets challenges in deep tissues. Herein, we propose an upconversion-driven photodynamic therapy combined with chemodynamic therapy based on UCNP@SiO₂@Fe₃O₄@MC540. Upon the excitation of 980 nm laser, the visible emission of upconversion nanoparticles activates MC540 to produce ROS, which is enhanced by Fe₃O₄ through magnetic field modulation. Subsequently, Fe₃O₄ degrades under acidic conditions to produce ·OH <em>via</em> Fenton-reaction for chemodynamic therapy. The <em>in vitro</em> and <em>in vivo</em> experiments indicate that the two-step cooperative strategy exhibits significant anticancer efficacy. Besides, Finite Difference Time Domain (FDTD) simulation reveals that the enhancement stems from surface electric field and light absorption. It offers a deeper understanding of phototherapeutic process.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"323 ","pages":"Article 107454"},"PeriodicalIF":3.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929247","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":"Characterization, antibacterial property, biocompatibility, and optimization of novel composite nanofibers incorporating curcumin-loaded flexible nano-liposomes","authors":"Hua-Wei Chen ,&nbsp;Chun-Hung Cheng ,&nbsp;Yu-Hsiang Yu ,&nbsp;Yi-Lin Chen ,&nbsp;Chyow-San Chiou ,&nbsp;Wei-Ting Chen","doi":"10.1016/j.bpc.2025.107453","DOIUrl":"10.1016/j.bpc.2025.107453","url":null,"abstract":"<div><div>Novel composite nanofibers incorporating curcumin-loaded flexible nano-liposomes (CLFN-liposomes) were developed for applications in tissue engineering, dressings, and drug delivery and release systems in this research. The preparation of CLFN-liposomes for curcumin encapsulation through the ethanol injection method was explored through a factorial experimental design. The optimal conditions for CLFN-liposomes/polycaprolactone composite nanofiber (CLFN-liposomes/PCL) were explored using the Taguchi method, emphasizing the addition of PCL, operational voltage, and flow rate. Uniformly distributed CLFN-liposomes with a smaller mean particle size of 53.9 ± 7.4 nm and higher encapsulation efficiency of 47.3 ± 3.4 % were synthesized for effective penetration. The smallest nanofiber diameter (186.3 ± 62.3 nm) with a smooth and uniform distribution was obtained after obtaining the optimum combinations of 17 wt% PCL, 4 wt% CLFN-liposomes/PCL, 25 kV, and 0.25 mL/h flow rate. The release of curcumin from CLFN-liposomes/PCL nanofibers followed the Higuchi model kinetics, with extended release for up to 48 h due to the dual-stage release from the nano-liposomes to the nanofibers. CLFN-liposomes/PCL dressings exhibited improved wettability (70.7° ± 4.3), water uptake (730 ± 44.2 %), biocompatibility (96 %), antimicrobial activity (41.8 ± 0.8 mm and 38.0 ± 1.1 mm inhibition zone of <em>Staphylococcus aureus</em> and <em>Escherichia coli</em>), and sustained release of curcumin, surpassing existing dressings in various aspects. This, novel composite nanofibers incorporating curcumin-loaded flexible nano-liposomes were developed, with promising wound dressing and broad application prospects. This study provides a novel idea for the release and delivery of active components through liposomes.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"323 ","pages":"Article 107453"},"PeriodicalIF":3.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143894648","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}