Journal of molecular graphics & modelling最新文献_第4页

Unveiling the potential of π-conjugated 2TT-R non-fullerene alternatives for multifunctional optoelectronic applications: A first-principles study 揭示π共轭2TT-R非富勒烯替代品在多功能光电应用中的潜力：第一性原理研究。

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling

Pub Date : 2026-01-12 DOI: 10.1016/j.jmgm.2026.109285

Sidra Manzoor , Nadeem Raza , Faheem Abbas

Organic solar cells (OSCs) offer lightweight, flexible, and cost−effective energy solutions. However, fullerene−based systems face limitations in stability, tunability, and absorption, prompting the exploration of non−fullerene alternatives to enhance efficiency and scalability. In this work, five newly designed molecules (2TT−1A to 2TT−5A) were systematically studied using Density Functional Theory (DFT) and Time−Dependent DFT (TD−DFT) at the B3LYP/6−311G (d, p) level in both gas and solvent (chloroform) phases. Key optoelectronic properties, including HOMO−LUMO gaps, absorption spectra, dipole moments, and excitation energies, were analyzed to evaluate their photovoltaic performance. All compounds demonstrated strong light−harvesting abilities, with a notable redshift in the absorption spectra observed in the solvent phase. Among them, 2TT−5A stood out with the narrowest energy gap (1.35 eV), the longest absorption wavelength (861 nm), the highest dipole moment (12.17 D), and the lowest excitation energy (1.43 eV), indicating efficient charge transfer and exciton dissociation. Open−circuit voltages (V_oc) ranging from 0.54 to 1.38 V also suggest good photovoltaic potential. Additionally, the nonlinear optical (NLO) and organic light−emitting diodes (OLED) properties of 2TT−5A were explored, revealing significant hyperpolarizability and a favorable emission profile. These results suggested that 2TT−5A is an exceptional multifunctional candidate, encouraging experimental synthesis and validating this material's stability, potentially accelerating the development of multifunctional organic optoelectronic devices.

有机太阳能电池（OSCs）提供了轻便、灵活、经济的能源解决方案。然而，基于富勒烯的系统在稳定性、可调性和吸收方面存在局限性，这促使人们探索非富勒烯替代品，以提高效率和可扩展性。本文采用密度泛函理论（DFT）和时间依赖DFT （TD-DFT）在B3LYP/6-311G （d, p）水平上对5种新设计的分子（2TT-1A至2TT-5A）在气相和溶剂（氯仿）相中进行了系统的研究。分析了关键光电性能，包括HOMO-LUMO间隙、吸收光谱、偶极矩和激发能，以评估其光伏性能。所有化合物都表现出很强的光收集能力，在溶剂相的吸收光谱中观察到明显的红移。其中，2TT-5A具有最窄的能隙（1.35 eV）、最长的吸收波长（861 nm）、最高的偶极矩（12.17 D）和最低的激发能（1.43 eV），表明其具有高效的电荷转移和激子解离。开路电压（Voc）范围从0.54到1.38 V也表明良好的光伏潜力。此外，研究了2TT-5A的非线性光学（NLO）和有机发光二极管（OLED）特性，揭示了显著的超偏振性和良好的发射分布。这些结果表明，2TT-5A是一种特殊的多功能候选材料，鼓励实验合成并验证该材料的稳定性，有可能加速多功能有机光电器件的发展。

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引用次数: 0

Exploring traditional Chinese medicine for antiviral drug discovery: A computational approach to combat human metapneumovirus (HMPV) 利用中药开发抗病毒药物：一种对抗人偏肺病毒（HMPV）的计算方法

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling

Pub Date : 2026-01-12 DOI: 10.1016/j.jmgm.2026.109290

Amit Dubey , Manish Kumar , Aisha Tufail , Vivek Dhar Dwivedi

Human metapneumovirus (HMPV) remains a major respiratory pathogen without approved antivirals, highlighting the urgent need for novel therapeutics. This study implemented an integrative computational pipeline combining virtual screening, molecular docking, 2 μs molecular dynamics (MD) simulations, density functional theory (DFT), pharmacophore modeling, and ADMET profiling to identify potent HMPV inhibitors from Traditional Chinese Medicine. Among 180 screened phytoconstituents, glycyrrhizin (–9.3 kcal mol⁻¹), hesperidin (–9.1 kcal mol⁻¹), and saikosaponins (–9.0 kcal mol⁻¹) exhibited strong binding affinities toward the HMPV matrix protein (PDB ID: 5WB0). Extended MD simulations confirmed complex stability with RMSD 0.17–0.22 nm, average of 3–5 persistent H-bonds, and DCCM correlation coefficient = 0.86 for glycyrrhizin. MM-PBSA binding free energies (ΔG_bind) of –46.2 ± 2.5, –44.7 ± 2.8, and –43.9 ± 2.2 kJ mol⁻¹ for glycyrrhizin, hesperidin, and oseltamivir respectively, validated strong and stable interactions. DFT results indicated favorable electronic reactivity (HOMO–LUMO gap = 3.86 eV; electrophilicity = 2.74 eV), enhancing ligand-target complementarity. ADMET analysis predicted low systemic toxicity (LD₅₀ = 380–530 mg kg⁻¹) but revealed moderate CYP3A4/CYP2C9 inhibition, suggesting the need for metabolic stability evaluation. Compared with reported fusion inhibitors such as EGCG and rutin, this matrix-targeted strategy introduces a distinct therapeutic mechanism. Overall, these findings establish a robust computational foundation for developing and experimentally validating potent natural inhibitors against HMPV.

人偏肺病毒（HMPV）仍然是一种主要的呼吸道病原体，尚未获得批准的抗病毒药物，这表明迫切需要新的治疗方法。本研究采用虚拟筛选、分子对接、2 μs分子动力学（MD）模拟、密度泛函数理论（DFT）、药效团建模和ADMET谱分析相结合的综合计算流程，鉴定中药中有效的HMPV抑制剂。在筛选的180种植物成分中，甘草酸（-9.3 kcal mol−1）、橙皮苷（-9.1 kcal mol−1）和柴草皂苷（-9.0 kcal mol−1）与HMPV基质蛋白（PDB ID: 5WB0）具有较强的结合亲和力。扩展的MD模拟证实了甘草酸配合物的稳定性，RMSD为0.17-0.22 nm，平均有3-5个持久氢键，DCCM相关系数为0.86。甘草酸、橙皮苷和奥司他韦的MM-PBSA结合自由能（ΔG_bind）分别为-46.2±2.5、-44.7±2.8和-43.9±2.2 kJ mol−1，证实了强而稳定的相互作用。DFT结果表明，良好的电子反应性（HOMO-LUMO间隙= 3.86 eV，亲电性= 2.74 eV），增强了配体-靶标的互补性。ADMET分析预测低全身毒性（LD50 = 380-530 mg kg - 1），但显示中度CYP3A4/CYP2C9抑制，提示需要代谢稳定性评估。与已有报道的融合抑制剂如EGCG和芦丁相比，这种基质靶向策略引入了一种独特的治疗机制。总的来说，这些发现为开发和实验验证抗HMPV的有效天然抑制剂建立了强大的计算基础。

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引用次数: 0

Y- and Zr-modified boron nitride nanosheets as efficient sensors for formamide: A first-principles approach Y和zr修饰的氮化硼纳米片作为甲酰胺的高效传感器：第一性原理方法

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling

Pub Date : 2026-01-12 DOI: 10.1016/j.jmgm.2026.109278

Meryem Derdare, Abdel-Ghani Boudjahem, Nedjoua Cheghib

This study employs DFT calculations to investigate the structural stability and electronic properties of pristine and transition-metal-doped boron nitride (BN) nanosheets, using yttrium (Y) and zirconium (Zr) as dopants, as well as their gas-sensing response toward formamide (FO). The findings show that introducing Y or Zr atoms leads to notable modifications in the electronic structure of the BN nanosheet, substantially improving its chemical reactivity and adsorption performance. In the aqueous phase, the interaction between FO and Y/Zr-doped BN nanosheets becomes moderately weaker, with adsorption energies decreasing to – 4.23 to – 24.97 kcal mol⁻¹; however, the most stable complexes still exhibit comparatively strong binding. Solvation also alters the electronic structure of the nanosheets, leading to noticeable variations in their energy gaps. Despite this reduction in interaction strength, both doped materials retain high sensitivity toward FO in water, with ZrBN reaching 99.9 %/1.43 × 10₃ % and YBN achieving 55.9 %/86.5 %. Moreover, the nanosheets exhibit extremely short recovery times in the liquid phase, with values of 1.27 × 10⁻¹⁵ s for ZrBN and 2.06 s for YBN, enabling rapid FO desorption and efficient restoration of active metal sites. These combined features confirm the strong potential of Y- and Zr-doped BN nanosheets as reusable and high-performance sensors for formamide detection in aqueous environments.

本研究采用DFT计算研究了原始和过渡金属掺杂的氮化硼（BN）纳米片的结构稳定性和电子性能，使用钇(Y)和锆（Zr）作为掺杂剂，以及它们对甲酰胺（FO）的气敏响应。研究结果表明，引入Y或Zr原子可以显著改变BN纳米片的电子结构，显著提高其化学反应性和吸附性能。在水相中，FO与掺杂Y/ zr的BN纳米片的相互作用变弱，吸附能降至- 4.23 ~ - 24.97 kcal mol−1；然而，最稳定的配合物仍然表现出相对强的结合。溶剂化也会改变纳米片的电子结构，导致其能隙的显著变化。尽管相互作用强度降低，但两种掺杂材料对水中FO的灵敏度都很高，ZrBN达到99.9% /1.43 × 103%， YBN达到55.9% / 86.5%。此外，纳米片在液相中表现出极短的恢复时间，ZrBN的值为1.27 × 10−15 s， YBN的值为2.06 s，能够快速解吸FO并有效恢复活性金属位。这些综合特性证实了Y和zr掺杂BN纳米片作为可重复使用的高性能传感器在水环境中检测甲酰胺的强大潜力。

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引用次数: 0

Structure-based discovery of novel TAOK3 inhibitor via virtual screening, molecular dynamics simulations, and MM/GBSA analysis 通过虚拟筛选、分子动力学模拟和MM/GBSA分析，发现基于结构的新型TAOK3抑制剂

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling

Pub Date : 2026-01-12 DOI: 10.1016/j.jmgm.2026.109286

Ali M. Alaseem , Glowi Alasiri , Mohamed M. El-Wekil , Al-Montaser Bellah H. Ali , Ahmed K. Hamdy

Cancer persists as a leading cause of global mortality, and the mitogen-activated protein kinase (MAPK) pathway plays a pivotal role in tumor progression and drug resistance. Among MAPK regulators, TAOK3 has emerged as a promising therapeutic target due to its oncogenic role in various cancers. Despite its significance, no clinically approved TAOK3 inhibitors exist. In this study we implemented a structure-based virtual screening approach to identify potential TAOK3 inhibitors from a library of 10,000 lead-like compounds. Molecular docking identified ten top-ranked candidates, with compound Z1 (ZINC ID: 77585305) demonstrating the strongest binding affinity (ΔG = −8.42 kcal/mol), outperforming reported inhibitors NCGC00188382 and SBI-581. ADMET profiling confirmed Z1's favorable drug-like properties, including high gastrointestinal absorption and minimal toxicity risks. Molecular dynamics simulations (100 ns) confirmed stable binding of Z1 to TAOK3, as indicated by low RMSD (<0.25 nm), consistent RMSF profiles, and compact radius of gyration. End-state free energy calculations using MM/GBSA also supported favorable binding, with Z1 showing excellent van der Waals interactions (−39.82 kcal/mol). Dynamic cross-correlation matrices and free energy landscape analysis further validated the stability of the TAOK3-Z1 complex. Collectively, these findings highlight Z1 as a promising TAOK3 inhibitor and a potential lead compound for further experimental validation in anticancer drug development.

癌症一直是全球死亡的主要原因，而丝裂原活化蛋白激酶（MAPK）途径在肿瘤进展和耐药性中起着关键作用。在MAPK调节因子中，TAOK3由于其在多种癌症中的致癌作用而成为一个有希望的治疗靶点。尽管具有重要意义，但尚未有临床批准的TAOK3抑制剂存在。在这项研究中，我们实施了一种基于结构的虚拟筛选方法，从10,000种铅样化合物的文库中鉴定潜在的TAOK3抑制剂。分子对接鉴定出10个排名前十位的候选化合物，其中化合物Z1（锌ID: 77585305）表现出最强的结合亲和力（ΔG =−8.42 kcal/mol），优于已报道的抑制剂NCGC00188382和SBI-581。ADMET分析证实了Z1有利的药物样特性，包括高胃肠道吸收和最小的毒性风险。分子动力学模拟（100 ns）证实了Z1与TAOK3的稳定结合，显示出低RMSD （<0.25 nm）、一致的RMSF分布和紧凑的旋转半径。用MM/GBSA计算的终态自由能也支持良好的结合，Z1表现出良好的范德华相互作用（- 39.82 kcal/mol）。动态互相关矩阵和自由能景观分析进一步验证了TAOK3-Z1配合物的稳定性。总的来说，这些发现突出了Z1作为一种有前途的TAOK3抑制剂和潜在的先导化合物在抗癌药物开发中的进一步实验验证。

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引用次数: 0

RLBindDeep: A ResNet-LSTM based novel framework for protein–ligand binding affinity prediction RLBindDeep：一个基于ResNet-LSTM的蛋白质配体结合亲和力预测新框架

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling

Pub Date : 2026-01-12 DOI: 10.1016/j.jmgm.2026.109282

Ekarsi Lodh , Shalini Majumder , Tapan Chowdhury , Manashi De

The prediction of the binding affinity of proteins and ligands in computational drug discovery with high accuracy is critical when evaluating the effectiveness of potential therapeutic compounds. This research work introduces RLBindDeep, a novel deep learning architecture based on the amalgamation of the ResNet and LSTM architectures, for improved accuracy in predicting protein–ligand binding affinities. Most traditional methodologies utilizing conventional molecular docking techniques suffer from poor accuracy owing to semi-flexible modeling approaches and limited considerations of complex interactions. On the other hand, RLBindDeep, which is formulated as a pose-independent binding affinity regression model that directly predicts experimental protein–ligand binding affinities from fixed complex structures, without performing docking or rescoring multiple poses, has performed well in extracting important features of the protein–ligand interaction. Specifically, the extracted features encompass ligand physicochemical descriptors (e.g., molecular weight, LogP, TPSA), protein-level features such as amino acid composition, and detailed interaction features including van der Waals, electrostatic, and hydrogen-bond energies. The model has been tested rigorously over the CASF-2016 benchmark dataset and has returned Pearson’s coefficient

R = 0.875

, Spearman’s coefficient

ρ = 0.864

, and Root Mean Square Error

RMSE = 0.993

. This significantly outperforms existing state-of-the-art models, such as HAC-Net and AutoDock Vina. Improved accuracy and robustness in RLBindDeep further highlight the possibility of deep learning to revolutionize computational drug discovery processes, making strategies for drug development more efficient and targeted.

在计算药物发现中，高精度地预测蛋白质和配体的结合亲和力对于评估潜在治疗化合物的有效性至关重要。本研究引入了RLBindDeep，这是一种基于ResNet和LSTM架构融合的新型深度学习架构，用于提高预测蛋白质-配体结合亲和力的准确性。由于半灵活的建模方法和对复杂相互作用的考虑有限，大多数利用传统分子对接技术的传统方法精度较差。另一方面，RLBindDeep是一种不依赖于姿态的结合亲和力回归模型，它可以直接预测固定复杂结构中实验蛋白与配体的结合亲和力，而不需要进行对接或重新记录多个姿态，在提取蛋白质与配体相互作用的重要特征方面表现良好。具体来说，提取的特征包括配体的物理化学描述符（如分子量、LogP、TPSA）、蛋白质水平特征（如氨基酸组成）和详细的相互作用特征（包括范德华、静电和氢键能）。该模型已在CASF-2016基准数据集上进行了严格测试，并返回Pearson系数R=0.875， Spearman系数ρ=0.864，均方根误差RMSE=0.993。这明显优于现有的最先进的模型，如HAC-Net和AutoDock Vina。RLBindDeep提高了准确性和鲁棒性，进一步强调了深度学习在彻底改变计算药物发现过程中的可能性，使药物开发策略更高效、更有针对性。

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引用次数: 0

Discovery of a novel PI3Kα inhibitor for breast cancer therapy via virtual screening method, molecular dynamics simulation and biological evaluation 通过虚拟筛选方法、分子动力学模拟和生物学评价发现一种新的乳腺癌治疗PI3Kα抑制剂

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling

Pub Date : 2026-01-12 DOI: 10.1016/j.jmgm.2026.109289

Thitiya Boonma , Bodee Nutho , Phongthon Kanjanasirirat , Chananya Rajchakom , Nadtanet Nunthaboot

Phosphatidylinositol-4,5-bisphosphate 3-kinase alpha (PI3Kα) is a central signaling enzyme driving cell proliferation and growth in cancers including breast cancer. Selective inhibition of PI3Kα isoform has become a promising therapeutic approach. In this work, 2000 in-house natural compounds were virtually screened against the ATP-binding site of PI3Kα. Of these, 618 compounds were predicted to have acceptable drug-likeness, pharmacokinetic, and toxicity properties based on in silico ADMET screening. Docking analysis highlighted four candidates forming stable hydrogen bonds with key residues V851, S854, and Q859 in the PI3Kα binding pocket. Molecular dynamics simulations were then used to assess their structural features and dynamic stability. Hit 2 was found to form strong hydrogen bonds with E849 and V851 of the PI3Kα protein. MM/GBSA-based binding free energy analysis supported that Hit 2 possessed the most favorable binding affinity to PI3Kα among the identified candidates. In vitro cytotoxicity assays were then performed in MCF-7 and MDA-MB-231 breast cancer cell lines, with alpelisib as a reference compound. Hit 2 reduced cell viability in both cell lines, but its effect was particularly pronounced in MDA-MB-231 cells, a model of triple-negative breast cancer (TNBC). These results suggest that Hit 2 represents a promising natural scaffold for further design and development in breast cancer therapy, with particular relevance for aggressive TNBC.

磷脂酰肌醇-4,5-二磷酸3-激酶α (PI3Kα)是驱动包括乳腺癌在内的癌症细胞增殖和生长的中心信号酶。选择性抑制PI3Kα异构体已成为一种很有前途的治疗方法。在这项工作中，2000种内部天然化合物对PI3Kα的atp结合位点进行了虚拟筛选。其中，618种化合物预测具有可接受的药物相似性、药代动力学和基于计算机ADMET筛选的毒性。对接分析显示，在PI3Kα结合口袋中，有4个候选分子与关键残基V851、S854和Q859形成稳定的氢键。然后用分子动力学模拟来评估它们的结构特征和动态稳定性。Hit 2与PI3Kα蛋白的E849和V851形成强氢键。基于MM/ gbsa的结合自由能分析结果表明，Hit 2与PI3Kα的结合亲和力最强。然后在MCF-7和MDA-MB-231乳腺癌细胞系中进行体外细胞毒性测定，以alpelisib为参比化合物。Hit 2降低了两种细胞系的细胞活力，但其作用在三阴性乳腺癌（TNBC）模型MDA-MB-231细胞中尤为明显。这些结果表明，Hit 2代表了一种有前途的天然支架，可以进一步设计和开发乳腺癌治疗，特别是与侵袭性TNBC相关。

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引用次数: 0

Investigating the effect of membrane pore size on the permeability of carbon nanotubes in reverse electrodialysis using molecular dynamics simulation 利用分子动力学模拟研究了反电渗析中膜孔径对碳纳米管渗透性的影响

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling

Pub Date : 2026-01-10 DOI: 10.1016/j.jmgm.2026.109281

Zishuo Zheng , N. Emami

Reverse electrodialysis (RED) is an emerging technology that converts the salinity gradient between seawater and freshwater into clean electrical energy. The efficiency of RED is strongly governed by ion transport through the membrane interface, where nanoscale geometry plays a decisive role. This study investigates, through molecular dynamics simulations, how the pore size of carbon nanotube (CNT) membranes influences water and ion permeability under an applied electric field. The simulation framework involved a two-stage procedure (30 ns equilibration at 300 K followed by dynamic evaluation of electrokinetic transport) to achieve stable atomic configurations and reliable transport data. Results revealed that as membrane pore size increased from 20 Å to 30 Å, both water flux and electric current increased significantly, indicating enhanced permeability and reduced flow resistance. However, this improvement was accompanied by a decline in hydrogen bond density from 103 to 86, implying weaker intermolecular cohesion and reduced structural confinement within larger pores. The mean-squared displacement of water molecules also increased, confirming increased molecular mobility and collision frequency. Although electric flow density decreased with pore enlargement due to charge dilution across a wider cross section, the overall voltage output rose from 21.02 to 24.54 μV. These findings demonstrate that optimizing pore geometry enables a balance between fluid transport efficiency and charge density, offering a molecular-scale understanding of how nanopore design can enhance RED performance, improve ion selectivity, and guide the development of next-generation nanoengineered membranes for sustainable energy harvesting.

反向电渗析（RED）是一项新兴技术，它将海水和淡水之间的盐度梯度转化为清洁的电能。RED的效率很大程度上取决于离子通过膜界面的传输，其中纳米尺度的几何形状起着决定性的作用。本研究通过分子动力学模拟研究了在外加电场作用下，碳纳米管（CNT）膜的孔径对水和离子渗透性的影响。模拟框架包括两个阶段的过程（300k下30ns平衡，然后是电动力学输运的动态评估），以获得稳定的原子构型和可靠的输运数据。结果表明，随着膜孔径从20 Å增大到30 Å，水通量和电流均显著增大，表明膜的渗透性增强，流阻降低。然而，这种改善伴随着氢键密度从103下降到86，这意味着更弱的分子间凝聚力和更大孔隙内的结构约束减少。水分子的均方位移也增加了，证实了分子迁移率和碰撞频率的增加。在更宽的截面上，由于电荷稀释，电流密度随着孔的扩大而降低，但总电压输出从21.02上升到24.54 μV。这些发现表明，优化孔隙几何结构可以实现流体传输效率和电荷密度之间的平衡，从而在分子尺度上理解纳米孔设计如何提高RED性能，提高离子选择性，并指导下一代纳米工程膜的可持续能量收集的开发。

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引用次数: 0

Molecular simulations of the tunable pore structure models elucidate the adsorption of sulfamethoxazole on biochar 可调孔结构模型的分子模拟阐明了磺胺甲恶唑在生物炭上的吸附

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling

Pub Date : 2026-01-10 DOI: 10.1016/j.jmgm.2026.109276

Zehui Zhang, Hong Wei, Feng Pan, Ruijie Teng, Junqi Song, Shujie Xie

Biochar is an environmentally friendly adsorption material that can effectively adsorb sulfamethoxazole (SMX) in water. However, the relationship between the pore structure characteristics of biochar and the SMX adsorption process remains unclear. In this study, molecular dynamics (MD) simulations combined with complementary experiments was employed to investigate SMX adsorption on four biochar models: isolated mesopores (BC1), micropores (BC2), hierarchical pores (BC3), and amorphous carbon (BC4). A remarkable concordance was observed between the MD simulations and experimental results. MD simulations revealed that porous structures facilitate SMX adsorption, leading to the fastest adsorption equilibrium rate for BC4. Additionally, a correlation between pore size and the SMX adsorption kinetics was observed. Within micropores, SMX achieves adsorption equilibrium at a slower rate, exhibiting a diffusion coefficient 62 % lower than that observed in mesopores. Noncovalent interaction (NCI) analysis and energy decomposition demonstrated that both π-π interactions and hydrogen bonds jointly stabilize SMX adsorption on biochar, with van der Waals interaction (contributing 59 %) playing a dominant role. Experimental results showed that the adsorption of SMX onto BBC-800 conformed to the Langmuir isotherm and pseudo-second-order kinetic model. Both simulations and experiments jointly elucidated the adsorption mechanism of SMX onto biochar, primarily involving pore filling, π-π stacking, and hydrogen bonding interactions. These findings provide atomic-scale insights for designing biochar with optimized pore structures for antibiotic removal.

生物炭是一种能有效吸附水中磺胺甲恶唑（SMX）的环保型吸附材料。然而，生物炭的孔隙结构特征与SMX吸附过程之间的关系尚不清楚。本研究采用分子动力学（MD）模拟和互补实验相结合的方法，研究了SMX在分离介孔（BC1）、微孔（BC2）、分层孔（BC3）和无定形碳（BC4）四种生物炭模型上的吸附。模拟结果与实验结果有显著的一致性。MD模拟表明，多孔结构有利于SMX的吸附，导致BC4的吸附平衡速率最快。此外，还观察到孔径大小与SMX吸附动力学之间的相关性。在微孔中，SMX以较慢的速率达到吸附平衡，其扩散系数比在中孔中低62%。非共价相互作用（NCI）分析和能量分解表明，π-π相互作用和氢键共同稳定了SMX在生物炭上的吸附，其中范德华相互作用（贡献59%）起主导作用。实验结果表明，SMX在bc -800上的吸附符合Langmuir等温线和拟二级动力学模型。模拟和实验共同阐明了SMX在生物炭上的吸附机理，主要涉及孔隙填充、π-π堆积和氢键相互作用。这些发现为设计具有优化孔结构的生物炭去除抗生素提供了原子尺度的见解。

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引用次数: 0

Evaluating the drug delivery potential of functionalized calix [4] arene for carboplatin-drug: A computational study analyzing static electric field and solvent effects through DFT, TD-DFT, and NLO techniques 评价功能化杯[4]芳烃对卡铂类药物的药物传递潜力：通过DFT、TD-DFT和NLO技术分析静电场和溶剂效应的计算研究

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling

Pub Date : 2026-01-09 DOI: 10.1016/j.jmgm.2026.109275

M. Rezaei-Sameti, M. Heydari

Targeted and precise drug delivery using nanomaterials remains a major goal in cancer therapy. In this study, the interaction of carboplatin, a key anticancer drug, with pristine and functionalized calix[4]arene (CHO, COOH, NH₂, NO₂) was investigated under varying solvent environments (water, ethanol, DMSO) and static electric fields (SEF) using density functional theory (DFT) at the GD3-Cam-B3LYP/Lanl2DZ level. The negative adsorption energy (E_ads) and enthalpy (ΔH) values confirm exothermic and thermodynamically favorable interactions across all complexes. Among them, CC-NO₂-II exhibits the highest E_ads (−32.54 kcal/mol in the gas phase), while CC-COOH derivatives demonstrate exceptional stability across solvents due to strong hydrogen bonding and dipolar interactions. Under SEF (z+0.05 a.u.), CC-NH₂ exhibits the most significant enhancement in E_ads (−276.01 kcal/mol), highlighting its potential for field-assisted drug delivery. The CC-COOH complex shows the greatest E_gap reduction (83.6 %), attributed to its high dipole moment and polarizability. Non-covalent interactions, including hydrogen bonding, van der Waals forces, and electrostatic interactions, were confirmed through atoms-in-molecules (AIM) and reduced density gradient (RDG) analyses. These findings underscore the potential of functionalized calix [4] arene as an efficient and tunable drug carrier, with external fields and solvents serving as effective modulation factors. This work provides valuable insights for the molecular design of advanced, field-responsive drug delivery systems for targeted chemotherapy applications.

利用纳米材料靶向和精确地给药仍然是癌症治疗的一个主要目标。本研究利用密度泛函理论（DFT）在GD3-Cam-B3LYP/Lanl2DZ水平上研究了抗癌药物卡铂在不同溶剂环境（水、乙醇、DMSO）和静电场（SEF）下与原始和功能化的瓶形[4]芳烃（CHO、COOH、NH2、NO2）的相互作用。负吸附能（Eads）和焓（ΔH）值证实了所有配合物的放热和热力学有利相互作用。其中，CC-NO2-II在气相中具有最高的Eads (- 32.54 kcal/mol)，而CC-COOH衍生物由于具有很强的氢键和偶极相互作用，在溶剂中具有优异的稳定性。在SEF （z+0.05 a.u.）下，CC-NH2在Eads中表现出最显著的增强（- 276.01 kcal/mol），突出了其在现场辅助给药方面的潜力。由于具有较高的偶极矩和极化率，CC-COOH配合物的Egap还原率最高（83.6%）。非共价相互作用，包括氢键、范德华力和静电相互作用，通过原子-分子（AIM）和降低密度梯度（RDG）分析得到了证实。这些发现强调了功能化杯芳烃作为一种高效可调的药物载体的潜力，外场和溶剂是有效的调节因素。这项工作为靶向化疗应用的先进、现场反应性药物输送系统的分子设计提供了有价值的见解。

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引用次数: 0

Computational modeling of ubiquitin specific protease 7 (USP7) complexes with N-benzylpiperidinol derivatives incorporating binding site flexibility 结合结合位点灵活性的n -苄基胡椒醇衍生物泛素特异性蛋白酶7 （USP7）配合物的计算建模

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling

Pub Date : 2026-01-08 DOI: 10.1016/j.jmgm.2025.109272

Jorge Luis Valdés-Albuernes, Erbio Díaz-Pico, José Luis Velázquez-Libera, Julio Caballero

Ubiquitin-specific protease 7 (USP7) is a key regulator of protein homeostasis, playing critical roles in various cellular processes, including DNA damage response, immune signaling, and oncogenesis. Targeting USP7 with small-molecule inhibitors has emerged as a promising therapeutic strategy, particularly in the context of cancer and autoimmune diseases. Among the diverse scaffolds explored for USP7 inhibition, N-benzylpiperidinol (NBP) derivatives have shown notable potential due to their structural versatility and bioactivity. Computationally, it is possible to access models of complexes between these inhibitors and USP7 by utilizing the crystallographic structures of USP7 available in the Protein Data Bank. In a classical approach, models of NBPs can be obtained within a rigid USP7 structure. In this work, we report models of complexes between 58 NBPs and variable conformations of USP7 using a flexible docking protocol employing the novel CorrEA method. As part of this protocol, we obtained diverse USP7 structures through molecular dynamics (MD) and selected complex models with inhibitors based on their biological activities. Model quality was validated using LigRMSD and interaction fingerprints (IFP). The flexible treatment of USP7 enabled the capture of binding-site conformational changes. These changes are critical for explaining the activity differences among the studied compounds.

泛素特异性蛋白酶7 （USP7）是蛋白质稳态的关键调节因子，在多种细胞过程中发挥关键作用，包括DNA损伤反应、免疫信号传导和肿瘤发生。用小分子抑制剂靶向USP7已成为一种有前景的治疗策略，特别是在癌症和自身免疫性疾病的背景下。在多种抑制USP7的支架中，n -苄基胡椒醇（NBP）衍生物由于其结构的通用性和生物活性而显示出显着的潜力。通过计算，利用蛋白质数据库中可用的USP7的晶体结构，可以获得这些抑制剂和USP7之间的复合物模型。在经典方法中，NBPs的模型可以在刚性USP7结构中获得。在这项工作中，我们报告了58个NBPs和USP7的可变构象之间的复合物模型，使用了一种灵活的对接协议，采用了新的CorrEA方法。作为该方案的一部分，我们通过分子动力学（MD）获得了不同的USP7结构，并根据其生物活性选择了具有抑制剂的复杂模型。采用LigRMSD和交互指纹（IFP）对模型质量进行验证。对USP7的灵活处理可以捕获结合位点的构象变化。这些变化对于解释所研究化合物之间的活性差异至关重要。

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引用次数: 0