Journal of molecular graphics & modelling最新文献

A first-principles study of hydrogen storage on MXene Mo2C monolayer MXene Mo2C单层储氢的第一性原理研究

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling

Pub Date : 2026-05-01 Epub Date: 2026-01-12 DOI: 10.1016/j.jmgm.2026.109283

Mohamed Bakhit, Sina Karimzadeh, Tien-Chien Jen

This study investigates the potential of Mo₂C MXene as a hydrogen storage material using density functional theory (DFT) and molecular dynamics (MD) simulations to examine its structural stability, electronic properties, and hydrogen adsorption behavior. The optimized Mo₂C structure exhibits a hexagonal lattice with favorable adsorption sites over Mo atoms and shows a surface area expansion of approximately 4 % after hydrogen loading while maintaining lattice symmetry. Thermodynamic stability is confirmed through adsorption energy calculations, which reveal a clear relationship between energy levels and hydrogen concentration. The results indicate that H₂ adsorption on Mo₂C is a thermodynamically favorable and exothermic process, with adsorption energies ranging from −0.184 to −0.528 eV, satisfying the criteria for practical hydrogen storage applications. Charge transfer analysis identifies Mo atoms as electron acceptors. Density of States (DOS) calculations reveal a near-zero band gap, confirming the metallic nature of Mo₂C, while Projected DOS (PDOS) and orbital maps show significant hybridization and electronic polarization among H, Mo, and C atoms. Charge density difference maps highlight effective charge redistribution with strong electric fields around Mo atoms. MD simulations further confirm the structural stability of the Mo₂C–H₂ system, showing minimal deformation during a 100 ps simulation and supporting efficient hydrogen adsorption. Overall, these findings establish Mo₂C MXene as a promising candidate for hydrogen storage applications and provide valuable insights for experimental validation and further development of sustainable energy storage technologies.

本研究利用密度泛函理论（DFT）和分子动力学（MD）模拟研究了Mo2C MXene作为储氢材料的潜力，以研究其结构稳定性、电子性能和氢吸附行为。优化后的Mo2C结构呈现六边形晶格，具有对Mo原子有利的吸附位点，并且在保持晶格对称性的情况下，氢负载后表面面积扩大了约4%。通过吸附能计算证实了热力学稳定性，揭示了能级与氢浓度之间的明确关系。结果表明，H2在Mo2C上的吸附是一个热力学有利的放热过程，吸附能在−0.184 ~−0.528 eV之间，满足实际储氢应用的标准。电荷转移分析确定Mo原子为电子受体。态密度（DOS）计算显示Mo2C的带隙接近于零，证实了Mo2C的金属性质，而投影态密度（PDOS）和轨道图显示H、Mo和C原子之间存在明显的杂化和电子极化。电荷密度差图突出了Mo原子周围强电场下的有效电荷重分布。MD模拟进一步证实了Mo2C-H2体系的结构稳定性，在100 ps的模拟中显示出最小的变形，并支持高效的氢吸附。总的来说，这些发现确立了Mo2C MXene作为储氢应用的有前途的候选者，并为实验验证和可持续储能技术的进一步发展提供了有价值的见解。

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引用次数: 0

In silico engineering of transaminase variants for enhanced biocatalytic conversion of an ACE inhibitor precursor 转氨酶变异体的硅工程以增强ACE抑制剂前体的生物催化转化

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling

Pub Date : 2026-05-01 Epub Date: 2026-01-27 DOI: 10.1016/j.jmgm.2026.109308

Mohammad Asad , Mohamed Usman , Anisha Ashokan, Naveen Kulkarni

Angiotensin-converting enzyme (ACE) inhibitors are widely prescribed for cardiovascular disorders, yet their conventional chemical synthesis involves multiple steps, high energy consumption, and poor stereoselectivity. In this work, we present a fully in silico framework for the computational design and prediction of transaminase (TA) variants capable of catalyzing the asymmetric amination of ethyl 2-oxo-4-phenylbutanoate (OPBE) to yield L-homophenylalanine ethyl ester (L-HPE), a key chiral intermediate in ACE inhibitor synthesis. A homology model of the Silicibacter transaminase (62.7 % identity to 5KR6) was constructed in its dimeric form. Eleven active-site variants were designed and screened through molecular docking, followed by 100 ns molecular dynamics simulations. The top variants SbTA10, SbTA01, and SbTA11 exhibited reactive distances below 6 Å, binding energies between −17.7 and −20.8 kcal/mol, and substrate RMSD values under 2.0 Å, indicating stable enzyme–substrate complexes. A composite QZ-score integrating productive conformations, binding energy, pocket contacts, and structural stability ranked SbTA10 highest (0.89), followed by SbTA01 (0.88) and SbTA11 (0.85). Free-energy profiles derived from umbrella sampling revealed binding minima of −10.2 kcal/mol (SbTA10) and −8.1 kcal/mol (SbTA11), suggesting distinct substrate retention characteristics that may influence catalytic turnover. Collectively, these results identify plausible transaminase variants with favorable structural and energetic features for the proposed OPBE to L-HPE transformation. This study presents a computational framework for predicting transaminase variants, providing a basis for rational biocatalyst design that warrants future experimental validation to confirm catalytic efficiency and stereoselectivity.

血管紧张素转换酶（ACE）抑制剂被广泛用于心血管疾病，但其传统的化学合成涉及多个步骤，高能量消耗，立体选择性差。在这项工作中，我们提出了一个全硅框架，用于计算设计和预测能够催化2-氧-4-苯基丁酸乙酯（OPBE）不对称胺化生成l -同苯丙氨酸乙酯（L-HPE）的转氨酶（TA）变体。l -同苯丙氨酸乙酯是ACE抑制剂合成中的关键手性中间体。以二聚体形式构建了硅酸菌转氨酶的同源性模型（与5KR6的同源性为62.7%）。通过分子对接设计筛选了11个活性位点变异，并进行了100ns分子动力学模拟。结果表明，SbTA10、SbTA01和SbTA11的反应距离小于6 Å，结合能在- 17.7和- 20.8 kcal/mol之间，底物RMSD值小于2.0 Å，表明酶-底物复合物稳定。综合生产构象、结合能、口袋接触和结构稳定性的综合qz得分，SbTA10最高（0.89），其次是SbTA01（0.88）和SbTA11（0.85）。伞式采样的自由能谱显示，结合最小值为- 10.2 kcal/mol （SbTA10）和- 8.1 kcal/mol (SbTA11)，表明不同的底物保留特性可能影响催化周转。总的来说，这些结果确定了具有有利的结构和能量特征的转氨酶变体，用于建议的OPBE到L-HPE的转化。本研究提出了一个预测转氨酶变异的计算框架，为合理的生物催化剂设计提供了基础，保证了未来的实验验证，以确认催化效率和立体选择性。

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引用次数: 0

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 : 2026-05-01 Epub 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

ClathPLM: Deep multi-view feature extraction with CNN and attention enhances clathrin protein identification ClathPLM：基于CNN和注意力的深度多视图特征提取增强了网格蛋白的识别。

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling

Pub Date : 2026-05-01 Epub Date: 2026-01-21 DOI: 10.1016/j.jmgm.2026.109307

Shuxin Song, Yusen Su, Qingyang Guo, Taigang Liu

Clathrin is a key structural protein in intracellular vesicle transport, mainly mediating clathrin-mediated endocytosis (CME) through trimeric assembly. Its functional abnormalities are closely associated with various diseases, including neurodegenerative disorders, tumor metastasis, and immune system dysregulation. Traditional experimental methods for identifying the presence of Clathrin have limitations such as high cost and time consumption. Therefore, it is particularly urgent to develop efficient and reliable computational methods to assist in Clathrin recognition. In this study, we propose a model named ClathPLM, which integrates sequence embeddings from three pre-trained protein language models (PPLMs), i.e., ProtT5, ProtBert, and ESM-3, and performs deep representation learning on each feature through an independent branch composed of a convolutional neural network (CNN) and a multi-head Attention (MHA) mechanism, finally fusing the representations of the three views to accomplish the classification task. To validate the effectiveness of this design, we further examined variants of the fusion strategy and attention mechanism. Evaluation results show that ClathPLM demonstrates excellent overall classification performance and robustness, surpassing current state-of-the-art methods. Moreover, the model performs strongly on an additional case-study dataset and shows good scalability on an extra vesicular transport proteins (VTPs) dataset. We anticipate that ClathPLM may contribute to a deeper understanding of the role of Clathrin in cellular regulation and disease mechanisms, and facilitate future biological studies as well as potential clinical applications.

网格蛋白是细胞内囊泡运输的关键结构蛋白，主要通过三聚体组装介导网格蛋白介导的内吞作用（CME）。其功能异常与多种疾病密切相关，包括神经退行性疾病、肿瘤转移、免疫系统失调等。传统的检测网格蛋白存在的实验方法存在成本高、耗时长等局限性。因此，开发高效可靠的计算方法来辅助网格蛋白识别显得尤为迫切。在本研究中，我们提出了一个名为ClathPLM的模型，该模型整合了ProtT5、ProtBert和ESM-3三个预训练蛋白语言模型（pplm）的序列嵌入，并通过由卷积神经网络（CNN）和头部注意（MHA）机制组成的独立分支对每个特征进行深度表征学习，最终融合三种视图的表征来完成分类任务。为了验证这一设计的有效性，我们进一步研究了融合策略和注意机制的变体。评估结果表明，ClathPLM具有出色的整体分类性能和鲁棒性，超过了目前最先进的方法。此外，该模型在额外的案例研究数据集上表现良好，并在额外的囊泡转运蛋白（vtp）数据集上显示出良好的可扩展性。我们期待ClathPLM可以为更深入地了解Clathrin在细胞调节和疾病机制中的作用做出贡献，并促进未来的生物学研究和潜在的临床应用。

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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 : 2026-05-01 Epub 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 : 2026-05-01 Epub 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

Evaluating the interactions of L-DOPA and droxidopa toward D3 dopamine receptor through computational study: A comparison with dopamine 通过计算研究评估左旋多巴和羟多巴对D3多巴胺受体的相互作用：与多巴胺的比较

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling

Pub Date : 2026-05-01 Epub Date: 2026-01-02 DOI: 10.1016/j.jmgm.2025.109270

Bhabesh Baro, Biplab Sarkar

The D

_{3}

dopamine receptor (D

_{3}

R), a member of the G protein-coupled receptor family, plays a critical role in neurophysiological processes and has emerged as a potential target for treating neurological disorders such as Parkinson’s disease. In this study, we employed computational approaches to investigate the molecular interactions of D

_{3}

R with dopamine and two key dopamine precursors: L-DOPA and droxidopa. Molecular docking was conducted to evaluate binding affinities and identify key receptor–ligand interactions, followed by molecular dynamics simulations to assess the stability and dynamic behavior of the complexes in a biological environment. MM-PBSA binding free energy calculations were used to further quantify the strength of ligand binding to D

_{3}

R.

D3多巴胺受体（D3R）是G蛋白偶联受体家族的一员，在神经生理过程中起着关键作用，并已成为治疗帕金森病等神经系统疾病的潜在靶点。在这项研究中，我们采用计算方法研究了D3R与多巴胺和两种关键多巴前体：左旋多巴和羟多巴的分子相互作用。通过分子对接来评估结合亲和力，识别关键的受体-配体相互作用，然后进行分子动力学模拟来评估配合物在生物环境中的稳定性和动态行为。MM-PBSA结合自由能计算进一步量化配体与D3R的结合强度。

引用次数: 0

Dynamic consequences of threonine mutations in the CaLM motif of RET/GFRα1/GDNF ternary complex RET/GFRα1/GDNF三元配合物CaLM基序苏氨酸突变的动态影响

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling

Pub Date : 2026-05-01 Epub Date: 2026-01-19 DOI: 10.1016/j.jmgm.2026.109301

Bithia R., George Priya Doss C.

The extracellular domain (ECD) of the RET receptor tyrosine kinase depends on its cysteine-rich domain (CRD) for calcium coordination, structural stability, and assembly with GFRα1 and GDNF. Mutations close to the CRD CaLM motif have been associated with disease, but their molecular effects remain understudied. In this study, we analyzed two clinically reported variants, T564N and T564P, using all-atom molecular dynamics simulations of both the isolated CRD and the RET/GFRα1/GDNF ternary complex. Our analysis showed that both the mutations introduced localized structural changes in the CRD monomer. T564N caused increased residue fluctuations at the mutation site and solvent exposure, whereas T564P enhanced flexibility across all calcium-coordinating residues and slightly decreased stabilizing contacts. These effects became more noticeable in the ternary complex. Within the complex, interactions with the neighbouring domains caused the CRD to adopt conformations that compensated for the structural changes observed in the CRD monomer. In this context, each mutation affected calcium-binding energetics differently, resulting in more favourable binding in the mutants than in the wild-type. Although calcium binding was energetically favourable, the overall interaction energy within the complex was still affected. The complex highlighted mutation-specific differences in RET's interactions with GFRα1 and GDNF. The comparison between monomeric and complex simulations indicates that the functional impact of T564 mutations cannot be inferred from the isolated CRD. Together, these results show that the structural and energetic consequences of CRD CaLM mutations depend strongly on the full signaling assembly. This underscores the need to assess RET variants within their native multiprotein environment to understand how disease-associated mutations may alter receptor function.

RET受体酪氨酸激酶的胞外结构域（ECD）依赖于其富含半胱氨酸的结构域（CRD）来进行钙的配位、结构稳定性以及与GFRα1和GDNF的组装。接近CRD - CaLM基序的突变与疾病有关，但其分子效应仍未得到充分研究。在这项研究中，我们分析了两个临床报道的变异，T564N和T564P，使用分离的CRD和RET/GFRα1/GDNF三元配合物的全原子分子动力学模拟。我们的分析表明，这两种突变都在CRD单体中引入了局部结构变化。T564N增加了突变位点和溶剂暴露的残基波动，而T564P增强了所有钙配位残基的灵活性，并略微减少了稳定接触。这些效应在三元配合物中更加明显。在复合物内，与邻近结构域的相互作用导致CRD采用构象，以补偿在CRD单体中观察到的结构变化。在这种情况下，每个突变对钙结合能量的影响不同，导致突变体比野生型更有利于钙结合。虽然钙结合在能量上是有利的，但复合物内的总相互作用能仍然受到影响。该复合体突出了RET与GFRα1和GDNF相互作用的突变特异性差异。单体和复杂模拟的比较表明，T564突变的功能影响不能从分离的CRD中推断出来。总之，这些结果表明，CRD - CaLM突变的结构和能量后果强烈依赖于完整的信号组装。这强调了在其原生多蛋白环境中评估RET变异体以了解疾病相关突变如何改变受体功能的必要性。

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引用次数: 0

Molecular dynamic simulation elucidates temperature- and pH-dependent film-forming mechanisms of soybean β-conglycinin and glycinin 分子动力学模拟阐明了大豆β-甘氨酸和甘氨酸的温度和ph依赖性成膜机制。

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling

Pub Date : 2026-05-01 Epub Date: 2026-01-16 DOI: 10.1016/j.jmgm.2026.109297

Meiling Liu , Yuan Zhao , Linfan Shi , Zhongyang Ren , Wuyin Weng , Meitian Xiao

The effects of temperature (25–95 °C) and pH (7.0–9.0) on the film-forming mechanisms of soybean β-conglycinin (7S) and glycinin (11S) were investigated using molecular dynamics (MD) simulations and experimental validation. All MD simulations achieved equilibrium within 50 ns. The elevated temperatures and lower pH conditions reduced the center-of-mass distance and the radius-of-gyration (Rg) between 7S and 11S, while increasing hydrogen bond formation and binding free energy. Solvent-accessible surface area decreased with temperature, while root-mean-square fluctuation remained stable at pH 7.0 but increased with temperature at pH 9.0. The 7S-11S films prepared at higher temperatures exhibited enhanced tensile strength and higher proportion of hydrophobic interactions. With increasing temperature of the 7S-11S solution, the elongation at break increased at pH 7.0, but initially increased and then decreased at pH 9.0. Fourier transform infrared spectra revealed that hydrogen bonds and β-sheet structures increased with increasing temperature. In conclusion, heating the film-forming solution at pH 7.0 promoted 7S-11S molecular interactions, thereby improving the mechanical properties.

采用分子动力学（MD）模拟和实验验证的方法，研究了温度（25 ~ 95℃）和pH（7.0 ~ 9.0）对大豆β-甘氨酸（7S）和甘氨酸（11S）成膜机理的影响。所有MD模拟均在50 ns内达到平衡。温度升高和pH降低降低了7S ~ 11S之间的质心距离和旋转半径（Rg），同时增加了氢键形成和结合自由能。溶剂可及表面积随温度升高而减小，均方根波动在pH 7.0时保持稳定，但在pH 9.0时随温度升高而增大。在较高温度下制备的7S-11S薄膜具有更高的拉伸强度和更高的疏水相互作用比例。随着7S-11S溶液温度的升高，断裂伸长率在pH 7.0时升高，但在pH 9.0时先升高后降低。傅里叶红外光谱显示，随着温度的升高，氢键和β-片结构增加。综上所述，在pH 7.0下加热成膜液促进了7S-11S分子间的相互作用，从而改善了材料的力学性能。

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引用次数: 0

Evaluation of CendR peptides mined from protein databases as potential inhibitors of neuropilin-1 using an in-silico molecular modeling approach 从蛋白质数据库中挖掘的CendR肽作为neuropilin-1的潜在抑制剂，使用硅分子建模方法进行评估。

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling

Pub Date : 2026-05-01 Epub Date: 2026-01-13 DOI: 10.1016/j.jmgm.2026.109279

Muslim Raza , Nurit Haspel , Anu Sharma , Sung Hugh Choi , Xavier De Luna , Jason J. Evans

Neuropilin 1 (NRP1) mediates lung branching angiogenesis and plays a vital role in cancer progression, especially in solid tumors. Its natural ligands, VEGFA and VEGFB, bind to the b1 binding pocket of NRP1 through hydrophilic c-terminus sites. Viral, bacterial and human proteins have evolved to interact with NRP1, facilitating entry into the cell, and therefore probing databases for hydrophilic CendR sequences could be a useful source of potential inhibitors of NRP1. Molecular docking was used to estimate the binding energies of 4185 naturally occurring CendR peptides to the b1 binding pocket of NRP1. The data predicts that proline, alanine, phenylalanine, leucine, tryptophan and tyrosine in the X positions of XXXXRXXR significantly strengthens the binding of the CendR peptides to the b1 binding pocket of NRP1 and that the presence of glutamic acid, lysine and serine tend to negatively impact binding. Three peptides predicted to have strong affinities and three peptides predicted to have weaker affinities were selected for molecular dynamic (MD) simulations. The data confirms that the interactions between the c-terminal arginine of these CendR peptides with several key residues, including Asp320, Thr316, Tyr297, and Tyr353, of the b1 binding site of NRP1 are particularly stable. During the MD simulations the three peptides predicted to be strong binders showed negative average free energies of interaction, while the three peptides predicted to bind more weakly showed positive free energies of interaction, providing validation of the docking results.

神经匹林1 （Neuropilin 1, NRP1）介导肺分支血管生成，在癌症进展中起重要作用，特别是在实体瘤中。它的天然配体VEGFA和VEGFB通过亲水性c端位点与NRP1的b1结合袋结合。病毒、细菌和人类蛋白质已经进化到与NRP1相互作用，促进进入细胞，因此探测亲水CendR序列的数据库可能是NRP1潜在抑制剂的有用来源。利用分子对接方法估计了4185个天然存在的CendR肽与NRP1 b1结合口袋的结合能。数据预测，XXXXRXXR X位的脯氨酸、丙氨酸、苯丙氨酸、亮氨酸、色氨酸和酪氨酸显著增强了CendR肽与NRP1 b1结合袋的结合，而谷氨酸、赖氨酸和丝氨酸的存在往往会对这种结合产生负面影响。选择亲和性较强的3个多肽和亲和性较弱的3个多肽进行分子动力学模拟。这些数据证实，这些CendR肽的c端精氨酸与NRP1 b1结合位点的几个关键残基（包括Asp320、Thr316、Tyr297和Tyr353）之间的相互作用特别稳定。在MD模拟中，预测为强结合的3个多肽的平均相互作用自由能为负，而预测为弱结合的3个多肽的平均相互作用自由能为正，为对接结果提供了验证。

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