Journal of molecular graphics & modelling最新文献_第7页

A quantum chemical investigation of potential applicability of X12Y12 (X= B, Al, C; Y= N, P, C) nanocages for efficient removal of levofloxacin through water 量子化学研究了X12Y12 （X= B, Al， C； Y= N， P， C）纳米笼在水中高效去除左氧氟沙星的潜在适用性。

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling

Pub Date : 2025-12-18 DOI: 10.1016/j.jmgm.2025.109260

Seyda Aydogdu

In the last years, growing human populations and economies have led to increasing environmental pollution, especially in water. Due to the adverse effects of antibiotics in the water environment, public concerns have increased about the health issue. For this reason, removal of antibiotic pollutants from the water environment is urgently needed. This work has been conducted in order to find a suitable adsorbent nanocage structure from X₁₂Y₁₂ (B₁₂N₁₂, Al₁₂N₁₂, B₁₂P₁₂, Al₁₂P₁₂, C₂₄) for removing levofloxacin antibiotic by using Density Functional Theory. The favorable adsorption processes are determined via adsorption energies and thermodynamic results for various orientations of levofloxacin onto the nanocages. The electronic nature of the adsorption processes is investigated with the help of Mulliken analysis, Natural Bond Orbital Analysis, and Quantum Theory of Atoms in Molecules. The reactivity and sensitivity investigation of the nanocage and levofloxacin complex systems is elucidated with global reactivity indices, Frontier Molecular Orbitals, Density of States spectra, and work function. The change of dipole moment values after adsorption are determined. The spontaneous characters of adsorption processes are determined. Furthermore, the number of LEV molecules, the water medium and the saline content of water effects the adsorption of LEV have been determined. The outcomes of this study demonstrate that Al₁₂N₁₂ and Al₁₂P₁₂ nanocages can be useable for effective removal of levofloxacin. The results of this study will be a novel contribution for further studies in order to remove levofloxacin effectively.

在过去的几年里，不断增长的人口和经济导致了越来越多的环境污染，特别是在水方面。由于抗生素对水环境的不良影响，公众对健康问题的关注日益增加。因此，迫切需要从水环境中去除抗生素污染物。本研究旨在利用密度泛函理论，从X12Y12 （B12N12, Al12N12, B12P12, Al12P12, C24）中寻找合适的吸附纳米笼结构，以去除左氧氟沙星抗生素。通过吸附能和热力学结果确定了左氧氟沙星在纳米笼上不同取向的吸附过程。利用Mulliken分析、自然键轨道分析和分子原子量子理论研究了吸附过程的电子性质。利用全局反应性指数、前沿分子轨道、态密度光谱和功函数对纳米笼-左氧氟沙星配合物体系的反应性和灵敏度进行了研究。测定了吸附后偶极矩值的变化。确定了吸附过程的自发特性。此外，还确定了LEV分子数、水介质和水中含盐量对其吸附的影响。本研究结果表明，Al12N12和Al12P12纳米笼可用于有效去除左氧氟沙星。本研究结果将为进一步有效去除左氧氟沙星的研究做出新的贡献。

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引用次数: 0

Machine learning-guided repurposing of FDA-approved quinolones as dual cholinesterase inhibitors: A multi-level docking, molecular dynamics, DFT, and SHAP-based analysis fda批准的喹诺酮类药物作为双胆碱酯酶抑制剂的机器学习指导：多层次对接，分子动力学，DFT和基于shap的分析。

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling

Pub Date : 2025-12-15 DOI: 10.1016/j.jmgm.2025.109259

Cüneyt Türkeş

Alzheimer's disease (AD) involves progressive cholinergic degeneration, with acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) playing key enzymatic roles in its pathology. In this study, we computationally repurposed four FDA-approved quinolone antibiotics, Norfloxacin, Sparfloxacin, Gatifloxacin, and Nalidixic acid, as potential dual-site cholinesterase (ChE) inhibitors using a hybrid in vitro/in silico workflow. Enzyme inhibition assays identified Norfloxacin as the most potent AChE inhibitor (K_I = 1.08 μM), while all compounds displayed non-competitive inhibition toward BChE. Molecular docking and MM-GBSA binding free energy analyses revealed key interactions within the catalytic gorge of AChE, supported by hydrogen bonding with Phe295 and Arg296, as well as π–π contacts with Tyr124. Density functional theory computations highlighted the influence of frontier orbital distribution on binding affinity, particularly for Norfloxacin and Sparfloxacin. An explicit-solvent molecular dynamics simulation of the AChE–Norfloxacin complex further confirmed the stability of the docking-derived binding mode over 100 ns. In an exploratory fashion, SHAP-based machine learning models were applied to a descriptor set derived from QikProp, SwissADME, and Jaguar outputs, suggesting that BBB-related indices and HOMO energy contribute to AChE inhibition, whereas the energy gap is more relevant for BChE; these trends, however, are constrained by the small four-compound dataset and should be regarded as hypothesis-generating. In silico ADME/Tox profiling indicated favorable oral drug-like properties, low predicted CYP450 inhibition liabilities, and physicochemical profiles compatible with CNS-oriented optimization, although passive BBB permeability was not predicted to be high. Finally, systems-level enrichment (STRING, GeneCards) provided a qualitative network context linking ACHE and BCHE to neurodegeneration. Together, these data position Norfloxacin and Sparfloxacin as computationally prioritised candidates whose ChE-related repurposing potential warrants further validation in dedicated cellular and in vivo models.

阿尔茨海默病（AD）涉及进行性胆碱能变性，乙酰胆碱酯酶（AChE）和丁基胆碱酯酶（BChE）在其病理中起关键作用。在这项研究中，我们使用体外/室内混合工作流程，计算重新利用四种fda批准的喹诺酮类抗生素，诺氟沙星，斯帕沙星，加替沙星和萘利地酸，作为潜在的双位点胆碱酯酶（ChE）抑制剂。酶抑制实验表明，诺氟沙星是最有效的AChE抑制剂（KI = 1.08 μM），而所有化合物对BChE均表现出非竞争性抑制作用。分子对接和MM-GBSA结合自由能分析揭示了AChE催化通道内的关键相互作用，包括与Phe295和Arg296的氢键，以及与Tyr124的π-π接触。密度泛函理论计算强调了前沿轨道分布对结合亲和力的影响，特别是对诺氟沙星和斯帕沙星。乙酰氨基酸-诺氟沙星配合物的显式溶剂分子动力学模拟进一步证实了对接衍生的结合模式在100 ns以上的稳定性。以探索性的方式，基于shap的机器学习模型应用于来自QikProp、SwissADME和Jaguar输出的描述符集，表明bbb相关指数和HOMO能量有助于AChE抑制，而能量缺口与BChE更相关；然而，这些趋势受到小的四复合数据集的限制，应该被视为假设生成。在硅ADME/Tox分析显示良好的口服药物样性质，低预测CYP450抑制负荷，和物理化学特征兼容的cns导向优化，虽然被动血脑屏障渗透率预测不高。最后，系统级富集（STRING, GeneCards）提供了将ACHE和BCHE与神经变性联系起来的定性网络上下文。总之，这些数据将诺氟沙星和斯帕沙星定位为计算优先的候选药物，其与che相关的再利用潜力值得在专门的细胞和体内模型中进一步验证。

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引用次数: 0

A computational study integrating antiviral peptide mediated inhibition of trafficking complex in Sesbania Mosaic Virus 整合抗病毒肽介导的田菁花叶病毒运输复合物抑制的计算研究。

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling

Pub Date : 2025-12-15 DOI: 10.1016/j.jmgm.2025.109258

Jyotilipsa Mohanty, Ayaluru Murali

Plant viruses pose a serious threat to global agriculture and although chemical, genetic, and biological control strategies exist, but each method have limitations in effectiveness and sustainability. Recently, the use of microbial peptides for curbing the movement of plant viruses has gained momentum. In this work, five peptides viz. Peptamine, indolicidin 10R, indolicidin 11R, Recombinant Thanatin (RT) and Recombinant Chimeric Lactoferricin + Lactoferrampin (RCLL), were identified and analysed for their role in disrupting the virus movement. The Sesbania Mosaic Virus (SeMV) is known to use a trafficking complex (a heteroprotein complex consisting of movement protein (MP), RdRp, VPg, and P10) for its intercellular movement. In this work, the ability of these peptides in binding to the major constituents of the trafficking complex (the MP and the RdRp) and their ability to disrupt the formation of trafficking complex was analysed using in silico tools. All five peptides were found to be disrupting the formation of the trafficking complex. Our findings suggest that these peptides can serve as potential antiviral agents by interfering with essential viral functions. This study provides new insights into peptide-based inhibition of plant viruses, offering an alternative to conventional control strategies.

植物病毒对全球农业构成严重威胁，尽管存在化学、遗传和生物防治策略，但每种方法在有效性和可持续性方面都有局限性。近年来，利用微生物肽抑制植物病毒的传播已成为研究热点。在这项工作中，鉴定并分析了五种肽，即Peptamine， indolicidin 10R, indolicidin 11R，重组Thanatin （RT）和重组嵌合乳铁蛋白+乳铁蛋白（RCLL），它们在破坏病毒运动中的作用。已知田菁花叶病毒（SeMV）使用运输复合体（由运动蛋白（MP）、RdRp、VPg和P10组成的异蛋白复合体）进行细胞间运动。在这项工作中，使用硅工具分析了这些肽与运输复合物（MP和RdRp）的主要成分结合的能力以及它们破坏运输复合物形成的能力。所有五种多肽都被发现破坏了运输复合物的形成。我们的研究结果表明，这些肽可以通过干扰基本的病毒功能作为潜在的抗病毒药物。该研究为基于多肽的植物病毒抑制提供了新的见解，为传统的控制策略提供了替代方案。

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引用次数: 0

In silico identification of food-grade cooling compounds targeting TRPM8 and TRPA1: A dual-target approach 针对TRPM8和TRPA1的食品级冷却化合物的硅基鉴定：双靶标方法。

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling

Pub Date : 2025-12-13 DOI: 10.1016/j.jmgm.2025.109257

Zhongwei Zhang , Jun Wang , Yu Liu , Xiangyu Li , Hao Shu , Jideng Chu , Zhangqi Chai , Junsong Xiao , Guangwen Ma , Hua Wu

Background

Oral mucosa is susceptible to pathological changes, including burning sensation, erythema, and inflammation, when exposed to thermal, mechanical, or chemical stimuli. These changes significantly impact oral comfort and health. To address the need for oral cooling agents, this study targets both TRPM8 and TRPA1 channels. We established a “computation-screening-validation” system using homology modeling and virtual screening to identify potential cooling agents from 555 natural flavorings approved for food use in China.

Results

High-quality homology models of TRPM8 and TRPA1 were constructed. Multi-stage virtual screening was then performed using molecular docking. This process incorporated pharmacokinetic properties, key physicochemical properties (water solubility and lipophilicity), and Protox3.0 toxicity predictions. The structural stability of promising ligand-target complexes was further evaluated via molecular dynamics simulations. The screening identified α-Terpineol, cis-Jasmone, and Benzyl Salicylate as promising candidates. These compounds demonstrated superior predicted binding affinities for both targets compared to other screened compounds and favorable safety profiles. Molecular dynamics simulations confirmed stable binding and structural compactness of these compounds within the TRPM8 and TRPA1 binding sites.

Conclusions

This dual-target in silico approach offers an efficient, systematic way to identify safe and effective cooling agents. It provides valuable insights for the development of temperature-sensing modulators by highlighting compounds that can simultaneously activate TRPM8 and TRPA1.

背景：当暴露于热、机械或化学刺激时，口腔黏膜易发生病理变化，包括烧灼感、红斑和炎症。这些变化显著影响口腔舒适和健康。为了解决口服冷却剂的需求，本研究同时针对TRPM8和TRPA1通道。我们建立了一个“计算-筛选-验证”系统，利用同源性建模和虚拟筛选，从中国批准用于食品的555种天然香料中筛选出潜在的冷却剂。结果：构建了高质量的TRPM8和TRPA1同源性模型。然后利用分子对接进行多阶段虚拟筛选。这个过程包括药代动力学性质、关键的物理化学性质（水溶性和亲脂性）和Protox3.0毒性预测。通过分子动力学模拟进一步评价了有前途的配体-靶配合物的结构稳定性。筛选结果表明α-松油醇、顺式茉莉酮和水杨酸苄酯是较有前途的候选物质。与其他筛选的化合物相比，这些化合物对这两个靶点的预测结合亲和力和良好的安全性。分子动力学模拟证实了这些化合物在TRPM8和TRPA1结合位点内的稳定结合和结构紧密性。结论：这种双靶点硅片方法提供了一种高效、系统的方法来鉴定安全有效的冷却剂。它通过突出可以同时激活TRPM8和TRPA1的化合物，为温度传感调节剂的开发提供了有价值的见解。

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引用次数: 0

(5,3) SWCNT-doping phosphorus-magnesium: Difference in adsorption of cardiovascular drugs （5,3） swcnts掺杂磷镁：心血管药物吸附的差异。

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling

Pub Date : 2025-12-12 DOI: 10.1016/j.jmgm.2025.109254

G. Dodero , E. Noseda Grau , A. Díaz Compañy , G. Román , S. Simonetti

The adsorption of hydrochlorothiazide and aspirin drugs onto a phosphorus (P) -magnesium (Mg) -doped (5,3) single-walled carbon nanotube (SWCNT) is investigated by density-functional theory (DFT) calculations using the Vienna Ab initio Simulation Package (VASP). The optimization of different structures indicates that the hydrochlorothiazide drug is stronger adsorbed than aspirin onto (5,3) SWCNT-P-Mg, affecting de release kinetics of the drugs. The results manifest the importance of the selected dopant atoms on the modification of the material surface in order to change the adsorption properties and the release conditions. We corroborate the results by means of electronic structure, density of states (DOS), frontier orbitals, and molecular electrostatic potential analysis.

利用维也纳从头算模拟包（VASP），通过密度泛函理论（DFT）计算，研究了磷(P) -镁（Mg）掺杂（5,3）单壁碳纳米管（SWCNT）对氢氯噻嗪和阿司匹林药物的吸附。不同结构的优化表明，氢氯噻嗪类药物比阿司匹林更强地吸附在（5,3）swcnts - p - mg上，影响药物的释放动力学。结果表明，掺杂原子的选择对于改变材料表面的吸附性能和释放条件具有重要意义。我们通过电子结构、态密度（DOS）、前沿轨道和分子静电势分析证实了结果。

引用次数: 0

Investigating the pH influence on insulin fibril stability: Molecular dynamics insights 研究pH值对胰岛素原纤维稳定性的影响：分子动力学见解

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling

Pub Date : 2025-12-09 DOI: 10.1016/j.jmgm.2025.109255

Yasaman Mahmoodi , Shirin Jalali , Shirin Shahabadi, Hamed Emami, Faramarz Mehrnejad

The research highlights the impact of pH on the structural stability of insulin amyloid fibrils, linked to clinical complications such as insulin-derived amyloidosis and potential insulin resistance. Using molecular dynamics (MD) simulations, we demonstrate that at neutral pH (pH 7), deprotonated glutamate residues create electrostatic repulsion within the fibril core. This reduces inter-protomer hydrogen bonding and leads to partial destabilization. In contrast, at acidic pH (pH 2), protonation of acidic residues diminishes repulsion, facilitating tighter packing and a more organized hydrogen-bond network. Further analyses, including hydration shell characterization and principal component analysis (PCA), underscore structural differences between fibrils under different pH conditions. At pH 7, the fibrils exhibit a more hydrated shell and greater collective motions, revealing reduced compactness and stability. Residues such as Leu, Glu, and Gln are crucial for fibril stability, with their hydrogen bonding participation notably reduced at neutral pH. These findings provide critical insights into the molecular mechanisms underlying the pH-dependent destabilization of insulin fibrils. Such a mechanistic understanding holds significant potential for guiding the development of therapeutic strategies aimed at preventing fibril formation or promoting controlled fibril disassembly. These advancements could help address the challenges posed by insulin-derived amyloidosis, thereby improving clinical outcomes for patients requiring recurrent insulin therapy.

该研究强调了pH值对胰岛素淀粉样蛋白原纤维结构稳定性的影响，这与胰岛素源性淀粉样变性和潜在的胰岛素抵抗等临床并发症有关。利用分子动力学（MD）模拟，我们证明了在中性pH （pH 7）下，去质子化的谷氨酸残基在原纤维核心内产生静电排斥。这减少了原聚体间的氢键并导致部分不稳定。相反，在酸性pH （pH 2）下，酸性残基的质子化减少了斥力，促进了更紧密的包装和更有组织的氢键网络。进一步的分析，包括水化壳表征和主成分分析（PCA），强调了不同pH条件下原纤维的结构差异。在pH值为7时，原纤维呈现出更水合的外壳和更大的集体运动，显示出降低的致密性和稳定性。Leu、Glu和Gln等残基对胰岛素原纤维的稳定性至关重要，它们的氢键参与在中性ph下明显减少。这些发现为胰岛素原纤维ph依赖性不稳定的分子机制提供了重要见解。这种机制的理解对于指导旨在防止纤维形成或促进控制纤维分解的治疗策略的发展具有重要的潜力。这些进展可以帮助解决胰岛素源性淀粉样变性带来的挑战，从而改善需要反复胰岛素治疗的患者的临床结果。

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引用次数: 0

Charge distribution defines the mechanism of fish gelatin-polysaccharide interactions 电荷分布决定了鱼明胶-多糖相互作用的机理

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling

Pub Date : 2025-12-09 DOI: 10.1016/j.jmgm.2025.109251

Elena Ermakova, Yuriy Zuev

The molecular mechanisms of fish gelatin (FG)-polysaccharide interactions are crucial for designing of advanced biomaterials. While experimental studies have demonstrated that polysaccharides can enhance the FG's functional properties, the atomic-level details of these interactions remain poorly characterized. In this study, we employ molecular docking to identify preferential binding sites of gelatin and the all-atom molecular dynamics (MD) simulations to quantify the interaction energetics and complex stability, with particular focus on the role of local charge distribution along gelatin molecule. We modeled four FG fragments with varying charge distribution and analyzed their interactions with anionic and cationic polysaccharides ι-carrageenan, alginate and chitosan. The MD simulations revealed that the charge density patterns of both interacting molecules critically determine gelatin-polysaccharide binding affinity and complex stability. This work provides first 3D-structural models of FG-polysaccharide complexes, offering fundamental insight for biomaterial design.

鱼明胶-多糖相互作用的分子机制对于设计先进的生物材料至关重要。虽然实验研究表明多糖可以增强FG的功能特性，但这些相互作用的原子水平细节仍然缺乏表征。在这项研究中，我们采用分子对接的方法来确定明胶的优先结合位点，并采用全原子分子动力学（MD）模拟来量化相互作用的能量学和配合物的稳定性，特别关注了明胶分子局部电荷分布的作用。我们模拟了四种不同电荷分布的FG片段，并分析了它们与阴离子和阳离子多糖ι-卡拉胶、海藻酸盐和壳聚糖的相互作用。MD模拟表明，两种相互作用分子的电荷密度模式决定了明胶-多糖的结合亲和力和复合物的稳定性。这项工作提供了fg -多糖复合物的第一个3d结构模型，为生物材料设计提供了基本的见解。

引用次数: 0

Fe- and Li-decorated hydrogen boride as a gas sensor for CO, NO, and CO2 detection: A DFT study 铁和锂装饰的硼化氢作为CO， NO和CO2检测的气体传感器：DFT研究

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling

Pub Date : 2025-12-09 DOI: 10.1016/j.jmgm.2025.109253

A. El Aiboudi , A. Sibari , Y. Kaddar , N. Masaif , H. Ez-Zahraouy

The development of high-performance gas sensors for detecting inorganic pollutants is vital for environmental protection. Using first-principles calculations, this study reveals that hydrogen boride (HB) monolayers exhibit remarkable sensitivity toward CO₂, CO, and NO, which is further enhanced by Fe and Li decoration. Li-decorated HB shows strong NO adsorption (Eads = −1.53 eV, charge transfer = 0.52 e), while Fe decoration greatly improves CO (Eads = −2.56 eV) and CO₂ (Eads = −2.74 eV) adsorption. Compared with other 2D materials such as graphene (−0.12 eV) and MoS₂ (−0.35 eV), Fe–HB displays adsorption strengths nearly one order of magnitude higher, highlighting its superior sensitivity and selectivity. Li–HB offers fast recovery suitable for CO₂ detection, whereas Fe–HB shows long desorption times favorable for capture. These results identify Li- and Fe-decorated HB monolayers as promising candidates for next-generation CO₂ sensing and capture technologies.

开发用于无机污染物检测的高性能气体传感器对环境保护具有重要意义。利用第一性原理计算，本研究揭示了硼化氢（HB）单层膜对CO2、CO和NO具有显著的敏感性，Fe和Li修饰进一步增强了这种敏感性。li修饰HB对NO有较强的吸附作用（Eads = - 1.53 eV，电荷转移= 0.52 e）， Fe修饰HB对CO （Eads = - 2.56 eV）和CO2 （Eads = - 2.74 eV）有较强的吸附作用。与石墨烯（- 0.12 eV）和MoS2 （- 0.35 eV）等其他二维材料相比，Fe-HB的吸附强度高出近一个数量级，突出了其优越的灵敏度和选择性。Li-HB具有适合于CO2检测的快速回收能力，而Fe-HB具有较长的解吸时间，有利于捕获。这些结果表明，锂和铁修饰的HB单层膜是下一代二氧化碳传感和捕获技术的有希望的候选者。

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引用次数: 0

Effect of chain length on the structure of aqueous surfactin solutions: Molecular dynamics studies 链长对表面素水溶液结构的影响：分子动力学研究

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling

Pub Date : 2025-12-08 DOI: 10.1016/j.jmgm.2025.109252

Loknath Patro, B.L. Bhargava

Surfactin, a highly effective biosurfactant synthesized by various strains of Bacillus subtilis, exhibits remarkable biological and physicochemical properties. Molecular dynamics simulations highlight the influence of hydrocarbon chain length on the micellar structure, aggregation behavior, hydrogen bonding patterns, and secondary structure of surfactin molecules. The findings reveal that the aggregates adopt an increasingly spherical shape as the hydrocarbon chain length increases. The aggregation number of surfactin molecules also increases with longer chain lengths, indicating enhanced clustering tendencies. In the peptide ring, the occurrence of

γ

-turn, identified by the intramolecular hydrogen bond between Leu2 – Val4 residues, decreases with increasing chain length. The

β

-turn, identified by hydrogen bond between Leu2–Asp5 does not exhibit a clear trend, though the maximum occurrence probability is observed in systems with surfactin having longer alkyl tail. The surface tension of surfactin solutions increases with chain length due to lower coverage of the surface in case of surfactins with longer tails due to the tilted orientation of their hydrophobic tails, which limits efficient packing.

表面活性剂是由多种枯草芽孢杆菌合成的高效生物表面活性剂，具有显著的生物学和理化性质。分子动力学模拟强调了烃链长度对表面素分子的胶束结构、聚集行为、氢键模式和二级结构的影响。结果表明，随着烃链长度的增加，聚集体呈球形。表面素分子的聚集数也随着链长的增加而增加，表明聚类倾向增强。在肽环中，γ-turn的发生随着链长的增加而减少，这是由Leu2 - Val4残基之间的分子内氢键所识别的。由Leu2-Asp5之间的氢键所确定的β-turn没有明显的变化趋势，但在具有较长烷基尾的表面素的体系中，β-turn的发生概率最大。表面素溶液的表面张力随着链长的增加而增加，这是由于在疏水尾部倾斜的情况下，具有较长尾部的表面覆盖率较低，这限制了有效的填充。

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引用次数: 0

Mechanistic study of the steric effect of Lewis acids AlCl3 and TiBr4 on the asynchronous [4+2] cycloaddition reaction of isoprene with Aryl acid: MEDT study 路易斯酸AlCl3和TiBr4对异戊二烯与芳基酸非同步[4+2]环加成反应的空间效应机理研究：MEDT研究。

IF 3 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling

Pub Date : 2025-12-05 DOI: 10.1016/j.jmgm.2025.109249

Tarik Boutadghart, Rachida Ghailane

The [4 + 2] cycloaddition reaction catalyzed by the Lewis acids AlCl3 and TiBr4 was systematically explored within the framework of Molecular Electron Density Theory (MEDT). The complete reaction pathway including reactants, transition states, and products was optimized and characterized using density functional theory (DFT) calculations at the SDD/M06/6–311++G (d,p) level. Conceptual DFT descriptors, combined with frontier molecular orbital (FMO) analysis, confirmed the nucleophilic role of isoprene and the electrophilic character of acrylic acid. Mechanistic insights revealed a one-step, concerted yet asynchronous process. The inclusion of Lewis acid catalysts markedly reshaped the reaction profile, enhancing both kinetic and thermodynamic features as well as regioselectivity. Notably, TiBr₄ decreased the activation barrier of the para transition state by 15.242 kcal mol⁻¹, whereas AlCl₃ increased the exothermic stabilization of the para adduct by 7.489 kcal mol⁻¹, thereby favoring the para pathway over the competing meta channel. Noncovalent interaction (NCI) analysis further highlighted stabilizing contacts, particularly through amino group interactions with protein residues, suggesting potential biological significance and bioactivity of the cycloadducts. Moreover, electron localization function (ELF) analysis underscored the decisive influence of steric effects, reinforcing that both catalyzed and uncatalyzed reactions proceed through an intrinsically asynchronous bond-formation mechanism.

在分子电子密度理论（MEDT）的框架下，系统地探讨了Lewis酸AlCl3和TiBr4催化的[4 + 2]环加成反应。利用密度泛函理论（DFT）在SDD/M06/6-311++G （d,p）水平上对包括反应物、过渡态和产物在内的完整反应途径进行了优化和表征。概念DFT描述子结合前沿分子轨道（FMO）分析，证实了异戊二烯的亲核作用和丙烯酸的亲电性。机械的洞察力揭示了一个一步，协调但异步的过程。Lewis酸催化剂的加入显著地改变了反应谱，增强了反应的动力学和热力学特征以及区域选择性。值得注意的是，TiBr4降低了对过渡态的激活势垒15.242 kcal mol-1，而AlCl3增加了对加合物的放热稳定性7.489 kcal mol-1，从而有利于对加合物途径而不是竞争性的元通道。非共价相互作用（NCI）分析进一步强调了稳定接触，特别是通过氨基与蛋白质残基的相互作用，表明了环加合物的潜在生物学意义和生物活性。此外，电子定位函数（ELF）分析强调了空间效应的决定性影响，强调了催化和非催化反应都是通过本质上异步的键形成机制进行的。

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引用次数: 0