检索结果-内蒙古大学图书馆

Duality of supercritical water pressure on phenol gasification studied by metadynamics simulation and experimental

FUEL 2025年 385卷

作者： Zhao, Deng Li, Xuetong Luo, Wei Li, Qingxin Han, Wenming Wang, Huashan Liu, Hua Liu, Hui Guo, Shuai Kou, Jiajing Yanshan Univ Hebei Engn Res Ctr Low Carbon Dev & Resource Utili Sch Vehicle & Energy Qinhuangdao 066004 Peoples R China Qinhuangdao Qinre Power Generat Co Ltd Hebei Circulating Fluidized Bed Boiler Thermal Pow Qinhuangdao 066000 Peoples R China Harbin Inst Technol Sch Energy Sci & Engn 92 West Da Zhi St Harbin 150001 Peoples R China Northeast Elect Power Univ Sch Energy & Power Engn Jilin 132012 Peoples R China

The gasification of phenol can be accelerated by the use of supercritical water (SCW) during the reaction, but continuously increasing the SCW pressure past a certain threshold will eventually inhibit this reaction. This paper reports the first use of metadynamics simulations to explain this mechanism by describing the waterline structure and fine structure of the phenol dimer better than reactive force field (ReaxFF). Discontinuous experiments showed that when increasing the SCW pressure from 23.5 MPa to 25.5 MPa, the reaction rate increased by 31 %, and when the pressure continued to increase to 29.5 MPa, the reaction rate decreased by 87 %, and then the reaction rate increased again at very high pressure. The simulation of single phenol molecule showed that the underlying reason that supercritical water promoted the gasification of phenol was the formation of waterline structures, which accelerated H transfer, disrupted of C structures, and polarized water molecules, thereby accelerating the gasification reaction. Multiple phenol molecules simulations and experiments showed that excess pressure drove dimer formation, the dimer also reduced the active sites of the benzene ring. A higher pressure formed a more complex dimer structure, which required more energy to destroy. Same law as the experiment, when the density of the supercritical water state in which the multiple phenol molecules is located rises from 0.706 g/cm3 to 0.868 g/cm3, the energy barrier to reach the transition state rises 94 kacl/mol. metadynamics simulations allowed for a more detailed description of the state of the SCW and its oxidation mechanism, thus describing how the environment influenced the reaction mechanism.

关键词： metadynamics simulation Supercritical water Phenol Gasification Waterline Quantum chemistry

来源：评论

学校读者我要写书评

暂无评论

Conformation Changes Associated with the Formation and Activation of Lysine Tyrosylquinone of LOXL2 Studied by metadynamics simulation

引用

ADVANCED THEORY AND simulationS 2024年第4期7卷

作者： Wang, Yiwen Lin, Lirui Xu, Li-Yan Li, En-Min Dong, Geng Shantou Univ Med Coll Dept Biochem & Mol Biol Shantou 515041 Peoples R China Shantou Univ Dept Bioinformat Med Coll Shantou 515041 Peoples R China Shantou Univ Med Coll Guangdong Higher Educ Inst Key Lab Mol Biol High Canc Incidence Coastal Area Shantou 515041 Peoples R China Shantou Univ Med Coll Canc Res Ctr Shantou 515041 Peoples R China Shantou Univ Med Coll Guangdong Prov Key Lab Infect Dis & Mol Immunopath Shantou 515041 Peoples R China Shantou Univ Med Informat Res Ctr Med Coll Shantou 515041 Peoples R China

Lysyl oxidase-like 2 (LOXL2) is a Cu2+-dependent amine oxidase that catalyzes the oxidative deamination of lysine residues of elastin and collagen to generate aldehyde groups. In the active state of LOXL2, its conserved catalytic domain has a lysine tyrosylquinone (LTQ) cofactor and a copper ion. LTQ is post-translationally derived from Lys653 and Tyr689 of LOXL2. In this study, well-tempered metadynamics simulations are used to investigate the conformation modulation from the inactive state to active state and obtain the free energy landscape. Interestingly, the simulations show that LTQ precursor residues cannot get close in Zn2+-bound LOXL2, whereas the copper ion binding triggers a conformation change to form an optional structure for LTQ biosynthesis. It is found that a prominent loop, consisting of residues 654-658, hinders the formation of LTQ in Zn2+-LOXL2 by preventing Lys653 from moving into active site of LOXL2, whereas this loop is relatively flexible in Cu2+-LOXL2. After the formation of LTQ, it needs to be activated by adjusting its position to be exposed to the solvent, thus allowing it to react with its substrate proteins. The results indicate that this process involves an intermediate state and that the activation of LTQ overcomes an energy barrier of 5.9 kcal mol-1. LOXL2, a Cu2+-dependent amine oxidase, catalyzes lysine residues' oxidative deamination in elastin and collagen. This study unveils Zn2+-bound LOXL2 inhibiting LTQ precursor proximity. Copper ion binding induces a conformational change, aiding LTQ biosynthesis. Loop flexibility (residues 654-658) in Cu2+-LOXL2 enables LTQ formation. LTQ activation involves an intermediate state, overcoming a 5.9 kcal mol-1 energy barrier. image

关键词： conformation changes lysyl oxidase-like 2 metadynamics simulation metal ions

来源：评论

学校读者我要写书评

暂无评论

Development of high-performance nitrile hydratase whole-cell catalyst by automated structure-and sequence-based design and mechanism insights

引用

Systems Microbiology and Biomanufacturing 2024年第3期4卷 882-894页

作者： Meng Li Dong Ma Jun Qiao Zhongyi Cheng Qiong Wang Zhemin Zhou Laichuang Han Key Laboratory of Industrial Biotechnology(Ministry of Education) School of BiotechnologyJiangnan UniversityWuxi 214122JiangsuChina Jiangnan University(Rugao)Food Biotechnology Research Institute RugaoJiangsuChina Ningbo Institute of Marine Medicine Peking UniversityNingboZhejiangChina

Nitrile hydratase(NHase)is a metalloenzyme that catalyzes the conversion of nitrile to amide and is widely used in the biocatalysis of bulk chemicals such as acrylamide and *** the thermostability,activity,and soluble expression of natural NHase is crucial for its industrial ***,conventional engineering strategies are often based on the design and evaluation of single-point mutations,followed by multiple rounds of iterative combinations,which are inefficient and difficult to predict the evolutionary direction of the combinatorial mutations due to epistatic *** this study,we used PROSS,an automated design tool based on structural and sequence information,to design a thermophilic NHase from Pseudonocardia thermophila JCM3095(PtNHase).By sequentially applying subunit-independent mutations,subunit-synergistic mutations,and single-point revertant mutations,we obtained the superior mutant A2B1-β*** mutant exhibited 1.4-fold and 2.3-fold higher activity towards acrylonitrile and 3-cyanopyridine,respectively,compared to the wild ***,A2B1-β221 showed a significant enhancement in ***,benefiting from the enhanced soluble expression,a high-performance whole-cell catalyst for NHase was ***,conventional molecular dynamics simulations and metadynamics simulations were employed to resolve the molecular mechanisms under-lying the high activity and thermostability of A2B1-β*** study not only provided highly efficient whole-cell catalyst for NHase,but also demonstrated the efficacy of utilizing automated design tools and molecular dynamics simulations in the engineering of heterologous multimeric proteins,offering valuable insights into their applicability.

关键词： Nitrile hydratase Whole-cell catalyst Protein design Soluble expression metadynamics simulation

来源：评论

学校读者我要写书评

暂无评论

15 Years of molecular simulation of drug-binding kinetics

引用

EXPERT OPINION ON DRUG DISCOVERY 2023年第12期18卷 1333-1348页

作者： Wong, Chung F. Univ Missouri St Louis Dept Chem & Biochem St Louis MO USA Univ Missouri St Louis Dept Chem & Biochem 1 Univ Blvd St Louis MO 63121 USA

IntroductionDrug-binding kinetics has been increasingly recognized as an important factor to be considered in drug discovery. Long residence time could prolong the action of some drugs while produce toxicity on others. Early evaluation of the binding kinetics of drug candidates could reduce attrition rate late in the drug discovery process. Computational prediction of drug-binding kinetics is useful as compounds can be evaluated even before they are made. However, simulation of drug-binding kinetics is a challenging problem because of the long-time scale involved. Nevertheless, significant progress has been *** coveredThis review illustrates the rapid evolution of qualitative to quantitative molecular dynamics-based methods that have been developed over the last 15 *** opinionThe development of new methods based on molecular dynamics simulations now enables computation of absolute association/dissociation rate constants. Cheaper methods capable of identifying candidates with fast or slow binding kinetics, or rank-ordering rate constants are also available. Together, these methods have generated useful insights into the molecular mechanisms of drug-binding kinetics, and the design of drug candidates with therapeutically favorable kinetics. Although predicting absolute rate constants is still expensive and challenging, rapid improvement is expected in the coming years with the continuing refinement of current technologies, development of new methodologies, and the utilization of machine learning.

关键词： Drug-binding kinetics Markov State Model metadynamics simulation milestoning simulation scaled, steered, or random accelerated molecular dynamics umbrella-sampling simulation weighted ensemble simulation machine learning

来源：评论

学校读者我要写书评

暂无评论

Interplay of hydrophobic and hydrophilic interactions in sequence-dependent cell penetration of spontaneous membrane-translocating peptides revealed by bias-exchange metadynamics simulations

引用

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 2020年第10期1862卷 183402-183402页

作者： Cao, Zanxia Liu, Lei Hu, Guodong Bian, Yunqiang Li, Haiyan Wang, Jihua Zhou, Yaoqi Dezhou Univ Inst Biophys Shandong Prov Key Lab Biophys Dezhou 253023 Peoples R China Dezhou Univ Coll Informat Management Dezhou 253023 Peoples R China Dezhou Univ Coll Phys & Elect Informat Dezhou 253023 Peoples R China Griffith Univ Sch Informat & Commun Technol Inst Glyc Parklands Dr Southport Qld 4222 Australia

Spontaneous Membrane Translocating Peptides (SMTPs) can translocate silently across the bilayer and, thus, have the best potential to improve the delivery of therapeutic molecules to cells without toxicity. However, how their translocation mechanisms are affected by a specific peptide sequence remains poorly understood. Here, bias-exchange metadynamics simulations were employed to investigate the translocation mechanisms of five SMTPs with the same composition of amino acids (LLRLR, LRLLR, LLLRR, RLLLR, and LRLRL). simulation results yield sequence-dependent free energy barrier using the FESs along the z-directional distance. An in-depth analysis of sequence-dependent interactions in different regions of the bilayers indicates that the free-energy barrier height of a specific sequence is resulted from the accessibility balance of isolated or clustered hydrophobic residues (L) and hydrophilic residues (R) that leads to different levels of resistance for moving of a peptide into the hydrophobic center of the membrane. At the maximal of the free-energy barrier, all peptides have a conformation parallel to the membrane surface with the barrier height determined by their affinity to the hydrophobic region. The appropriate bilayer perturbation and GDM(+) pairing are beneficial for peptide translocation. These results provide an improved microscopic understanding of how peptide sequence influences the translocation efficiency and mechanism.

关键词： Spontaneous Membrane Translocating Peptides metadynamics simulation Translocation free energy Translocation mechanism

来源：评论

学校读者我要写书评

暂无评论

A higher flexibility at the SARS-CoV-2 main protease active site compared to SARS-CoV and its potentialities for new inhibitor virtual screening targeting multi-conformers

引用

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS 2022年第19期40卷 9214-9234页

作者： Rocha, Rafael E. O. Chaves, Elton J. F. Fischer, Pedro H. C. Costa, Leon S. C. Grillo, Igor Barden Da Cruz, Luiz E. G. Guedes, Fabiana C. Da Silveira, Carlos H. Scotti, Marcus T. Camargo, Alex D. Machado, Karina S. Werhli, Adriano V. Ferreira, Rafaela S. Rocha, Gerd B. De Lima, Leonardo H. F. Univ Fed Minas Gerais Inst Biol Sci Dept Biochem & Imunol Lab Mol Modeling & Drug Design Belo Horizonte MG Brazil Salzburg Univ Dept Mol Biol Lab Struct Biol Salzburg Austria Univ Fed iba Dept Chem Lab Computat & Quantum Chem Joao Pessoa Brazil Univ Fed Sao Joao Rei Dept Exact & Biol Sci Lab Mol Modeling & Bioinformat Sete Lagoas Brazil Lab Nacl Computacao Cientif Comp Modeling Coordinat Petropolis Brazil Univ Fed Itajub Inst Technol Sci Structural Bioinformat Lab Itabira Brazil Grad Program Nat & Synthet Bioact Prod Joao Pessoa Brazil Univ Fed Paraiba Joao Pessoa Brazil Univ Fed Rio Grande Ctr computat Sci Computat Biol Lab Rio Grande Brazil

The main-protease (M-pro) catalyzes a crucial step for the SARS-CoV-2 life cycle. The recent SARS-CoV-2 presents the main protease (M-pro(CoV2)) with 12 mutations compared to SARS-CoV (M-pro(CoV2)). Recent studies point out that these subtle differences lead to mobility variances at the active site loops with functional implications. We use metadynamics simulations and a sort of computational analysis to probe the dynamic, pharmacophoric and catalytic environment differences between the monomers of both enzymes. So, we verify how much intrinsic distinctions are preserved in the functional dimer of M-pro(CoV2), as well as its implications for ligand accessibility and optimized drug screening. We find a significantly higher accessibility to open binding conformers in the M-pro(CoV2) monomer compared to M-pro(CoV2). A higher hydration propensity for the M-pro(CoV2) S2 loop with the A46S substitution seems to exercise a key role. Quantum calculations suggest that the wider conformations for M-pro(CoV2) are less catalytically active in the monomer. However, the statistics for contacts involving the N-finger suggest higher maintenance of this activity at the dimer. Docking analyses suggest that the ability to vary the active site width can be important to improve the access of the ligand to the active site in different ways. So, we carry out a multiconformational virtual screening with different ligand bases. The results point to the importance of taking into account the protein conformational multiplicity for new promissors anti M-pro(CoV2) ligands. We hope these results will be useful in prospecting, repurposing and/or designing new anti SARS-CoV-2 drugs.

关键词： SARS-CoV COVID 19 metadynamics simulation multiconformational drug targeting quantum calculations

来源：评论

学校读者我要写书评

暂无评论

Investigation of Bound Water in Clay Based on Isothermal Adsorption Experiments and metadynamics Studies from the Perspective of Water Potential

引用

JOURNAL OF GEOTECHNICAL AND GEOENVIRONMENTAL ENGINEERING 2024年第11期150卷

作者： Zhang, Siqi Pei, Huafu Ploetze, Michael Zhang, Chao Tan, Daoyuan Hong Kong Polytech Univ Dept Civil & Environm Engn Hung Hom Hong Kong 999077 Peoples R China Dalian Univ Technol Sch Civil Engn State Key Lab Coastal & Offshore Engn Dalian 116026 Peoples R China Swiss Fed Inst Technol Inst Geotech Engn ClayLab Stefano Franscini Pl 3 CH-8093 Zurich Switzerland Hunan Univ Coll Civil Engn Changsha 410012 Hunan Peoples R China Nanjing Univ Sch Earth Sci & Engn Nanjing 210023 Peoples R China

The presence of bound water in clay has a significant impact on the physical and chemical properties of clay, particularly its strength, permeability, and creep behavior. In this paper, the bound water in clay has been studied from the perspective of water potential. Initially, the adsorption isotherms of powders and consolidated samples for Na- and Ca-bentonite and illite were measured, and the bound water content was determined by subtracting the capillary water in the isotherms, with the capillary water being calculated by mercury intrusion porosimetry tests. The results indicated that bound water is independent of the void ratio and pore structure of clay, which is consistent with previous studies. Then, metadynamics was conducted to determine the adsorption free energy landscapes of the three clays, and the lowest suctions of the three clay minerals were determined to be -1.7, -5.4, and -2.1 GPa, respectively. Finally, through a comparison of the simulations and experiments in this study and in the literature, three important conclusions were drawn. Firstly, the lowest water potential for montmorillonite exhibits a linear relationship with the hydration free energy of exchangeable cations. Secondly, the critical water potential for tightly bound water is determined as the first inflection point in the relationship between water potential and water content, and the critical value of montmorillonite is found to be correlated to the valence of exchangeable cations. Lastly, the boundary between loosely bound water and capillary water is determined as the starting point of capillary water formation. Overall, this research highlights the importance of considering water potential as a key factor in understanding the behavior of bound water in clay.

关键词： Bound water Water potential Adsorption isothermal experiment metadynamics simulation Free energy Clay

来源：评论

学校读者我要写书评

暂无评论

Prediction of The Binding Mode of NP-G2-044 Targeting Fascin and Its Drug Resistance Mutations

引用

ADVANCED THEORY AND simulationS 2024年第1期7卷

作者： Pan, Jinmei Wang, Liangdong Xu, Li-Yan Li, En-Min Dong, Geng Shantou Univ Med Coll Dept Biochem & Mol Biol Shantou 515041 Peoples R China Shantou Univ Med Coll Guangdong Higher Educ Inst Key Lab Mol Biol High Canc Incidence Coastal Area Shantou 515041 Peoples R China Shantou Univ Med Coll Canc Res Ctr Shantou 515041 Peoples R China Shantou Univ Med Coll Guangdong Prov Key Lab Infect Dis & Mol Immunopath Shantou 515041 Peoples R China Shantou Univ Med Coll Med Informat Res Ctr Shantou 515041 Peoples R China

Fascin is a major actin-binding protein (ABP) in filopodia and is highly expressed in metastatic tumors. To inhibit its function, a potent inhibitor called NP-G2-044 is currently in phase II clinical trials. However, the binding mode of this inhibitor remains unclear. In this study, the binding mode of NP-G2-044 in fascin and predicted drug resistance mutations is investigated. The rough binding position and pose can be deduce based on information from its derivant NP-G2-029, whose crystal structure with fascin has been solved. Molecular docking, free energy perturbation (FEP) simulation and metadynamics simulation are performed to confirm the binding pose. Based on the molecular docking results, two binding modes of NP-G2-044, pose A and B, are obtained, with pose A being more favorable. For pose A, the planar indazole moiety has the same orientation as NP-G2-029 in the complex with fascin, while for pose B, it rotates approximate to 90 degrees. FEP and metadynamics simulations indicate that both binding poses are possible. Relative binding free energies for mutation effects calculated by FEP predict E215A and R217A are drug resistance mutations. These findings are important for further drug development targeting fascin. This study investigates the binding mode of NP-G2-044 in fascin and predict drug resistance mutations. Two poses are obtained. For pose A, the planar indazole moiety has the same orientation as NP-G2-029 in the complex with fascin, while for pose B, it rotates approximate to 90 degrees. E215A and R217A are drug resistance ***

关键词： drug resistance mutation fascin free energy perturbation metadynamics simulation molecular dynamics simulation

来源：评论

学校读者我要写书评

暂无评论

Design of new drug delivery platform based on surface functionalization of black phosphorus nanosheet with a smart polymer for enhancing the efficiency of doxorubicin in the treatment of cancer

引用

JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A 2021年第10期109卷 1912-1921页

作者： Hashemzadeh, Hassan Raissi, Heidar Univ Birjand Dept Chem Birjand Iran

The development of drug delivery systems (DDSs) has raised hopes for targeted cancer therapy. Smart polymers can be conjugated with several nanoparticles and increase their efficiency in biomedical applications. In this work, the classical molecular dynamics and well-tempered metadynamics simulations are performed to study the behavior of black phosphorus (BPH) nanosheet functionalized with polyethylenimine (PEI) in adsorption, diffusion, and release of doxorubicin (DOX) anticancer drug. Adsorption of the drug on PEI-BPH surface is mainly due to the formation of strong pi-pi interaction between the drug and BPH. The drug-binding to the nanosheet is enhanced by the intermolecular hydrogen bond that formed between DOX and PEI. The energy values for the interaction of DOX with BPH and PEI are calculated to be about - 180 and - 50 kJ/mol, respectively. The obtained results indicated that the adsorption of the drug molecules on the nanosheet destroyed the hydration layer around the BPH- PEI surface. The free energy calculation for DDS shows a global minimum in which the distances of DOX from BPH surface and PEI are about 1.0 and 0.5 nm, respectively. Furthermore, the diffusion of DDS into the membrane has a macropinocytosis pathway that is in line with experimental observations. Moreover, it is found that, unlike the isolated DOX, the drug in complex with BPH-PEI can be easily penetrated membrane cells. The study of the pH-responsive release of the drug shows the high solubility of the polymer in the water environment plays the main role in swelling of DDS and the release of the DOX molecules.

关键词： free energy calculation metadynamics simulation pH-responsive polyethylenimine surface functionalization

来源：评论

学校读者我要写书评

暂无评论

Virtual screening by 2-D fingerprints, shape and docking for discovering new chemotypes of activator protein-1 inhibitors

引用

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS 2021年第7期39卷 2455-2462页

作者： Yin, Zhou Rutgers State Univ Waksman Inst Piscataway NJ 08854 USA Rutgers State Univ Dept Chem & Chem Biol Piscataway NJ 08854 USA

Activator protein-1 Fos/Jun proteins bind to cognate DNA and regulate gene expression. Small-molecule inhibitors targeting activator protein-1 DNA binding have been developed in the past decades for therapeutic applications. Recent structural andin silicostudies suggest a putative inhibitor binding pocket on the activator protein-1 structure, and computational modeling suggests a consensus binding mode of three classes of known small-molecule inhibitors. Here, virtual screening of two-dimensional fingerprints, shape, and docking was performed in search of novel chemotypes of activator protein-1 inhibitors. A standard score (Z(3)-score) coalescing top-ranked ligands from the three methods was used and the top-scoring ligands were clustered by similarity. A representative ligand from each large cluster was evaluated using metadynamics simulations and molecular mechanics calculations. Representative hits showed diverse chemotypes and their modeled binding pose on activator protein-1 reproduced key interactions with binding site residues. Communicated by Ramaswamy H. Sarma

关键词： Activator protein-1 virtual screening fingerprints docking data fusion metadynamics simulation

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：