Biophysical chemistry最新文献

iAFP-fLRM: Accurate identification of antifungal peptides via hybrid deep learning architecture and multi-modal feature fusion iAFP-fLRM：通过混合深度学习架构和多模态特征融合准确识别抗真菌肽

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2026-02-04 DOI: 10.1016/j.bpc.2026.107591

Shengli Zhang , Jianwei Cheng , Guixu Zhou , Jianhua Wang

Fungal infections (mycoses) represent a significant and increasing global health concern, particularly in immunocompromised populations. The emergence of antifungal drug resistance and the limited efficacy of conventional treatments necessitate the development of novel therapeutic strategies. Antifungal peptides (AFPs), due to their broad-spectrum activity, low toxicity, and reduced likelihood of resistance development, have garnered considerable attention as potential alternatives. However, the experimental identification of AFPs remains costly, labor-intensive, and time-consuming. To address this challenge, we propose iAFP-fLRM, a hybrid deep learning framework for AFP prediction based solely on amino acid sequences. The model integrates BLOSUM62-based evolutionary features, token embeddings, positional embeddings, and a Transformer encoder, with a subsequent LSTM-ResMLP classification module to capture both global contextual.

information and local sequential dependencies. Notably, we design a dual-branch feature fusion module that integrates adaptive pooling alignment and cross-branch attention enhancement: the former dynamically aligns sequence lengths without information loss, while the latter adaptively adjusts the contribution of heterogeneous features to enhance complementarity. Extensive evaluations on benchmark datasets demonstrate that iAFP-fLRM achieves superior performance compared to state-of-the-art methods in terms of accuracy, the area under the receiver operating characteristic curve, and Matthews correlation coefficient. Ablation studies confirm the complementary effectiveness of combining handcrafted and learned features. Furthermore, t-SNE visualizations of the latent representations illustrate the model's ability to distinguish AFPs from non-AFPs. Overall, iAFP-fLRM provides a robust and scalable computational tool for in silico AFP identification, with the potential to facilitate antifungal peptide discovery and accelerate the development of novel antifungal therapeutics. The datasets and code used in this research are available at https://github.com/blue-tsuki/iAFP-fLRM.

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引用次数: 0

Magnesium phosphate-induced structural and dynamic modulation of model membranes in the presence and absence of vitamin D₂: Insights from FTIR analyses 磷酸镁诱导模型膜在维生素D 2存在和不存在时的结构和动态调节：来自FTIR分析的见解

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2026-02-04 DOI: 10.1016/j.bpc.2026.107589

Neslihan Toyran , Feride Severcan

Biological membranes are complex structures whose structure and dynamics are modulated by various biomolecules, including ionic and sterol-like compounds. In this study, we investigated the molecular interactions of magnesium phosphate, in the absence and presence of vitamin D_2, with simplified models of biological membranes composed of dipalmitoylphosphatidylcholine (DPPC). We aimed to elucidate their individual and combined effects on the order and dynamics (fluidity) of the hydrophobic part and the interfacial region using Fourier Transform Infrared (FTIR) spectroscopy. Our findings show that the phase transition temperature of the model membrane is not measurably affected by the presence of magnesium phosphate and/or vitamin D₂. Our results also demonstrate that magnesium phosphate disrupts membrane integrity by decreasing the order of the pure DPPC and increasing the flexibility of the acyl chains in the deep interior of the bilayer, but, interestingly, it decreases membrane fluidity. These contradictory results on the order and dynamics of DPPC suggest a magnesium phosphate-induced phase separation in the membrane. Our findings also reveal that vitamin D₂ enhances lipid order and reduces acyl chain mobility of the pure DPPC. In the joint presence of magnesium phosphate and vitamin D₂, vitamin D₂ counteracts the disordering effects of magnesium phosphate and restores membrane stability. Consequently, it abolishes the magnesium phosphate-induced phase separation. In addition, our findings reveal a decrease in the strength of hydrogen bonding in the interfacial region, which is explained by the presence of free carbonyl groups in all model membrane combinations. Overall, this study advances our understanding of how multivalent ion–phosphate species and hydrophobic micronutrients jointly regulate membrane organization, extending prior findings on free ion–vitamin D interactions to the less-explored case of magnesium phosphate.

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引用次数: 0

Assessing the inhibitory effect of lyophilised tomato extract on lysozyme fibrillation: Spectrochemical and microscopic analysis 评估冻干番茄提取物对溶菌酶纤维的抑制作用：光谱化学和显微分析

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2026-01-23 DOI: 10.1016/j.bpc.2026.107582

Arindam Das , Shukdeb Sing , Gouranga Jana , Anirban Basu

Anti-amyloidogenic potential of tomato extract was explored using hen egg white lysozyme as model protein. Total polyphenolic content was determined to ensure the reported bio-activeness of tomato extract. Various spectroscopic and microscopic methods were employed to assess its anti-amyloidogenic property. Thioflavin T and congo red assays revealed dose dependent inhibition of lysozyme amyloid fibrillation. Furthermore, nile red and 8-anilino-1-naphthalenesulfonic acid assays confirmed less alteration in protein surface hydrophobicity during fibrillation in presence of tomato extract. Intrinsic fluorescence measurement also supported a steady reduction in fibril formation in presence of the tomato extract. Atomic force microscopic imaging clearly demonstrated that tomato extract significantly mitigated lysozyme fibrillation.

以蛋清溶菌酶为模型蛋白，探讨番茄提取物的抗淀粉样蛋白潜能。测定总多酚含量，以保证所报道的番茄提取物的生物活性。采用各种光谱和显微方法评价其抗淀粉样变性的性能。硫黄素T和刚果红测定显示溶菌酶淀粉样纤维性颤动的剂量依赖性抑制。此外，尼罗红和8-苯胺-1-萘磺酸测定证实，在番茄提取物的存在下，蛋白质表面疏水性的变化较小。固有荧光测量也支持在番茄提取物存在下纤维形成的稳定减少。原子力显微镜成像清楚地表明，番茄提取物显著减轻溶菌酶纤颤。

引用次数: 0

High-resolution AFM imaging of the CA125 protein and its aptamer-based complexes CA125蛋白及其适配体复合物的高分辨率AFM成像。

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2026-01-22 DOI: 10.1016/j.bpc.2026.107580

M.O. Ershova, A.A. Valueva, T.O. Pleshakova

An approach to evaluate the efficiency of aptamer/antigen complexation based on high-resolution AFM imaging data is proposed. The formation of specific complexes is the basis of diagnostic systems in medicine. It is shown that a comprehensive evaluation of the height and volume of objects sorbed on the surface of freshly cleaved mica from the solution of proteins and their complexes allows us to assess the success of complex formation in solution. The applicability of the approach is demonstrated using two variants of the CA125 antigen (containing seven or one full-length SEA domain) and two aptamers. The SEA domain is the binding contact in the antibody- or aptamer-mediated biorecognition system.

提出了一种基于高分辨率AFM成像数据评估适体/抗原络合效率的方法。特异性复合物的形成是医学诊断系统的基础。结果表明，综合评价从蛋白质及其复合物溶液中吸附在新切割云母表面的物体的高度和体积，可以评估溶液中复合物形成的成功程度。使用CA125抗原的两个变体（包含七个或一个全长SEA结构域）和两个适体证明了该方法的适用性。SEA结构域是抗体或适配体介导的生物识别系统中的结合接触。

引用次数: 0

Conformations of polyglutamate chains near single walled carbon nanotubes 单壁碳纳米管附近的聚谷氨酸链构象

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2026-01-20 DOI: 10.1016/j.bpc.2026.107581

Sayan Karmakar, Parbati Biswas

Carbon nanotubes possess multi-functional characteristics due to their unique physiochemical properties. All atom, explicit-solvent molecular dynamics simulations is used to explore the conformations of the polyglutamate chains of different lengths and its surface interactions with single walled carbon nanotubes of different diameters. The adsorption of the polyglutamate chains on the surface of these carbon nanotubes is governed by two critical ratios that depends on the geometric parameters of the polyglutamate chains and the carbon nanotubes. The

α

-helical content of the polyglutamate chains decreases with the increase in diameter of the carbon nanotubes. The number of intramolecular hydrogen bonds in the polyglutamate chains decrease upon adsorption on the surface of the nanotubes as compared to those in its absence. Polyglutamate adsorption on carbon nanotubes is largely due to van der Waals interactions. Shorter polyglutamate chains are more prone to adsorption. The distribution of water molecules for the adsorbed polyglutamate chains show that adsorption is governed by hydrophilic interactions.

碳纳米管由于其独特的理化性质而具有多功能的特点。采用全原子、显式溶剂分子动力学模拟研究了不同长度的聚谷氨酸链的构象及其与不同直径的单壁碳纳米管的表面相互作用。谷氨酸链在碳纳米管表面的吸附受两个临界比的控制，这两个临界比取决于谷氨酸链和碳纳米管的几何参数。聚谷氨酸链α-螺旋含量随碳纳米管直径的增加而降低。在纳米管表面吸附聚谷氨酸链时，分子内氢键的数量比在没有氢键的情况下减少。谷氨酸在碳纳米管上的吸附主要是由于范德华相互作用。较短的谷氨酸链更容易被吸附。吸附的聚谷氨酸链的水分子分布表明，吸附受亲水性相互作用支配。

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引用次数: 0

Spectroscopic, quantum chemical, and antibacterial studies on novel push–pull chromophore 3-(4-nitrophenyl)-3H-quinazolin-4-one 新型推挽发色团3-（4-硝基苯）- 3h -喹唑啉-4-酮的光谱、量子化学和抗菌研究。

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2026-01-14 DOI: 10.1016/j.bpc.2026.107578

Rani Mariam Cherian, C. Ravikumar

The title compound 3-(4-nitrophenyl)-3H-quinazolin-4-one (NPQ) was comprehensively characterized using FT-IR, Raman, and UV–vis spectroscopy. The compound was optimized in both solvent and gas phases using DFT/B3LYP method with 6–311++ G (d, p) as basis set. The calculated geometrical parameters and vibrational wavenumbers showed good agreement with the corresponding experimental results. Details about the charge density distribution and chemically reactive sites of the compound in both gas and solvent phase has been obtained by MEP mapping and Mulliken charge analysis. NBO analysis examines the unique charge transfer interactions inside the molecule. ELF and LOL investigations visualize localized and delocalized electrons in NPQ. The physical attributes ADMET (adsorption, distribution, metabolism, elimination, and toxicity) of the compound were calculated. The in vitro antibacterial activities of NPQ were studied and showed perceptible efficiency against E. coli and Pseudomonas aeruginosa. These experimental findings were supported with molecular docking studies which revealed strong binding energies and favorable interactions within the active site, suggesting a plausible mechanism for its antibacterial activity.

标题化合物3-(4-nitrophenyl)- 3h -quinazolin-4-one （NPQ）通过FT-IR、Raman和UV-vis光谱进行了全面表征。以6-311++ G （d, p）为基组，采用DFT/B3LYP法对化合物进行溶剂和气相优化。计算得到的几何参数和振动波数与实验结果吻合较好。通过MEP作图和Mulliken电荷分析，获得了化合物气相和溶剂相的电荷密度分布和化学反应位点的详细信息。NBO分析检查分子内独特的电荷转移相互作用。ELF和LOL研究可视化NPQ中的局域和非局域电子。计算了化合物的物理属性ADMET（吸附、分布、代谢、消除和毒性）。研究了NPQ的体外抑菌活性，对大肠杆菌和铜绿假单胞菌均有明显的抑菌效果。这些实验结果得到了分子对接研究的支持，发现活性位点具有强结合能和良好的相互作用，这可能是其抗菌活性的合理机制。

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引用次数: 0

Structural and functional insights into Vitamin D receptor mutations: An in-silico investigation of polymorphism-induced resistance 维生素D受体突变的结构和功能见解：多态性诱导抗性的计算机研究

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2026-01-14 DOI: 10.1016/j.bpc.2026.107579

Mohtashim Lohani , Nizar Ahmad Khamjan , Sajad Ahmad Dar , Farrukh Aqil , Saif Khan , Arshad Jawed , Saba Beigh , Iffat Zareen Ahmad

Vitamin D is critical for calcium homeostasis, bone health, and immune regulation via the Vitamin D Receptor. Mutations in the ligand-binding domain and DNA-binding domain can disrupt ligand interactions, causing biologically active metabolite of vitamin D [1α,25-dihydroxyvitamin D3 (calcitriol)] resistance and clinical complications such as hereditary rickets and immune dysregulation. This study explored the structural and functional effects of VDR missense mutations using computational approaches. An AlphaFold-generated VDR model incorporated selected mutations from 503 reported variants, of which 62 were likely pathogenic. Ten LBD mutations were analyzed. Molecular docking assessed Vitamin D3 binding, while molecular dynamics simulations, Root Mean Square Deviation, Radius of Gyration, and Principal Component Analysis evaluated structural stability. CASTp analyses identified key residues in the binding pocket, and downstream non-genomic pathways were assessed to interpret functional effects. Mutations R → H and R → L at position 274, and H → Q at position 305, exhibited minimal RMSD and Rg fluctuations, indicating stable protein conformations. Docking revealed reduced binding affinities (−8.9, −8.8, −9.0 kcal/mol) relative to wild-type (−9.9 kcal/mol), suggesting altered ligand-binding geometry. Other mutations showed greater structural deviations, indicating potential impairment of receptor function. Functional analysis suggested disruption of signaling essential for calcium homeostasis, bone mineralization, and immune regulation. These results demonstrate that missense mutations in the VDR LBD compromise Vitamin D3 binding and receptor stability, contributing to resistance and related skeletal and immune abnormalities. Computational modeling offers a framework to identify pathogenic variants and guide therapeutic strategies, including small molecules, peptide therapies, CRISPR-Cas9 editing, or Vitamin D analogs to restore receptor function and improve clinical outcomes.

维生素D通过维生素D受体对钙稳态、骨骼健康和免疫调节至关重要。配体结合域和dna结合域的突变可破坏配体相互作用，引起维生素D [1α，25-二羟基维生素D3（骨化三醇）]的生物活性代谢物耐药和遗传性佝偻病、免疫失调等临床并发症。本研究利用计算方法探讨了VDR错义突变的结构和功能影响。alphafold生成的VDR模型包含了从503个报告的变异中选择的突变，其中62个可能是致病的。分析了10个LBD突变。分子对接评估了维生素D3结合，而分子动力学模拟、均方根偏差、旋转半径和主成分分析评估了结构稳定性。CASTp分析确定了结合袋中的关键残基，并评估了下游非基因组途径来解释功能效应。突变R→H和R→L在274位，H→Q在305位，RMSD和Rg波动最小，表明稳定的蛋白质构象。对接显示，与野生型（−9.9 kcal/mol）相比，结合亲和度（−8.9,−8.8,−9.0 kcal/mol）降低，表明配体结合几何形状发生了改变。其他突变表现出更大的结构偏差，表明受体功能的潜在损害。功能分析表明，钙稳态、骨矿化和免疫调节所必需的信号被破坏。这些结果表明，VDR LBD中的错义突变会损害维生素D3结合和受体的稳定性，从而导致耐药性和相关的骨骼和免疫异常。计算建模提供了一个框架来识别致病变异并指导治疗策略，包括小分子、肽疗法、CRISPR-Cas9编辑或维生素D类似物，以恢复受体功能并改善临床结果。

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引用次数: 0

Heterotypic phase separation in aggregation: Driver or deterrent? 聚集中的异型相分离：驱动因素还是阻碍因素？

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2026-01-12 DOI: 10.1016/j.bpc.2026.107577

Tina Jacob , Wolfgang Hoyer

Liquid–liquid phase separation (LLPS) of proteins implicated in neurodegenerative diseases has gained growing attention in recent years, due to its potential role in driving the transition from functional protein monomers to pathogenic aggregates. However, the mechanisms by which phase separation contributes to the loss of protein function and promotes aggregation remain poorly understood. Recent studies show that multiple proteins or other biomolecules can colocalize within the biomolecular condensates, creating a highly interactive microenvironment that can modulate aggregation. In this review we look into the heterotypic phase separation of tau and α-synuclein, the two key proteins responsible for critical neurodegenerative disorders. By compiling recent findings, this review highlights the modulatory role of heterotypic condensates in disease progression and aims to provide an alternative perspective on regulation of protein aggregation in neurodegeneration.

近年来，与神经退行性疾病有关的蛋白质的液-液相分离（LLPS）受到越来越多的关注，因为它在驱动从功能蛋白单体到致病聚集体的转变中具有潜在作用。然而，相分离导致蛋白质功能丧失和促进聚集的机制仍然知之甚少。最近的研究表明，多种蛋白质或其他生物分子可以在生物分子凝聚物中共定位，创造一个高度相互作用的微环境，可以调节聚集。在这篇综述中，我们研究了tau和α-突触核蛋白的异型相分离，这两个关键蛋白负责关键的神经退行性疾病。通过整理最近的研究结果，本综述强调了异型凝聚体在疾病进展中的调节作用，并旨在为神经变性中蛋白质聚集的调节提供另一种视角。

引用次数: 0

Changes in the concentration of phosphatidylcholine in lipid bilayers determines the aggregation rate of transthyretin 脂质双分子层中磷脂酰胆碱浓度的变化决定了转甲状腺素的聚集速率

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2026-01-08 DOI: 10.1016/j.bpc.2026.107574

Abid Ali, Mikhail Matveyenka, Dmitry Kurouski

Transthyretin (TTR) is a tetrameric transporter of retinol and thyroxine that aggregates in the central and peripheral nervous system upon a severe pathology known as transthyretin amyloidosis. Although small molecular weight drugs can stabilize TTR preventing its aggregation, molecular mechanisms of transthyretin amyloidosis remain poorly understood. Accumulating evidence indicates that lipids can alter TTR stability by facilitating protein aggregation into toxic oligomers and fibrils. Consequently, pathological changes in the lipid composition of plasma membranes can be responsible for the onset and progression of transthyretin amyloidosis. In this study, we investigated the role of concentration-dependent changes in phosphatidylcholine (PC), one of the most abundant phospholipids in the plasma membrane, on the rate of TTR aggregation. For this, TTR was exposed to large unilamellar vesicles (LUVs) composed of 30%, 35%, and 40% PC. We found that a decrease in the concentration of PC from 40% to 35% drastically accelerated TTR aggregation. We also observed an increase in the cytotoxicity of TTR aggregates formed in the presence of 35% PC compared to TTR fibrils grown in the presence of LUVs with 40% PC. These results indicate that changes in the concentration of PC in the plasma membrane could trigger amyloid formation that leads to transthyretin amyloidosis.

甲状腺转蛋白（TTR）是视黄醇和甲状腺素的四聚体转运体，在中枢和周围神经系统中聚集，导致严重的甲状腺转蛋白淀粉样变。虽然小分子量药物可以稳定TTR，防止其聚集，但转甲状腺蛋白淀粉样变的分子机制仍然知之甚少。越来越多的证据表明，脂质可以通过促进蛋白质聚集成有毒的低聚物和原纤维来改变TTR的稳定性。因此，质膜脂质组成的病理改变可能是甲状腺转蛋白淀粉样变的发生和发展的原因。在本研究中，我们研究了质膜中最丰富的磷脂之一磷脂酰胆碱（PC）的浓度依赖性变化对TTR聚集率的作用。为此，将TTR暴露于由30%、35%和40% PC组成的大单层囊泡（LUVs）中。我们发现，PC浓度从40%下降到35%会急剧加速TTR的聚集。我们还观察到，与在含有40% PC的LUVs中生长的TTR原纤维相比，在35% PC存在下形成的TTR聚集体的细胞毒性增加。这些结果表明，质膜中PC浓度的变化可能引发淀粉样蛋白的形成，从而导致转甲状腺素淀粉样变性。

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引用次数: 0

Interactions of surfactin with ether-linked and ester-linked lipid membranes: A molecular dynamics simulation study 表面素与醚链和酯链脂质膜的相互作用：分子动力学模拟研究

IF 2.2 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-12-29 DOI: 10.1016/j.bpc.2025.107567

Boggarapu Manasa , Loknath Patro , B.L. Bhargava

Surfactin is a biosurfactant with diverse applications, including antibacterial and antiviral activity, primarily attributed to its ability to destabilize lipid bilayers. Previous studies have focused on ester-linked lipids, where destabilization has been associated with reduced hydration around ester carbonyl groups. Here, we employ molecular dynamics simulations to investigate surfactin’s effect on ether-linked lipids, which lack carbonyl groups and are characteristic of archaeal membranes known for their exceptional stability. We compared tetraether lipids and a diether lipid along with its ester-linked analogue. Among the ether-linked systems, the macrocyclic tetraether lipid showed the strongest response to surfactin insertion, whereas the diether lipid was minimally perturbed. By contrast, the ester-linked analogue underwent significant compression and increased water penetration into the bilayer. These findings reveal that membrane susceptibility to surfactin depends critically on both linkage chemistry and lipid architecture, with ester linkages and tetraether backbones promoting destabilization to a greater extent than diether systems.

表面素是一种具有多种应用的生物表面活性剂，包括抗菌和抗病毒活性，主要归因于其破坏脂质双分子层的能力。以前的研究主要集中在酯链脂质上，其中不稳定与酯羰基周围水合作用的减少有关。在这里，我们采用分子动力学模拟来研究表面素对醚连接脂质的影响，这种脂缺乏羰基，是古细菌膜的特征，以其卓越的稳定性而闻名。我们比较了四醚脂质和二醚脂质及其酯链类似物。在醚连接体系中，大环四醚脂质对表面素插入的响应最强，而二醚脂质对表面素插入的干扰最小。相比之下，酯连接的类似物经历了显著的压缩和增加水渗透到双分子层。这些发现表明，膜对表面素的敏感性主要取决于键化学和脂质结构，酯键和四醚骨架比二醚系统更大程度上促进不稳定。

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引用次数: 0