Both a molecule dynamic study and a combined quantum mechanics and mole-cule mechanics（QM/MM） study on the acetylating deactivation mechanism of isoniazid were presented.This type of reaction was catalyzed by arylam...Both a molecule dynamic study and a combined quantum mechanics and mole-cule mechanics（QM/MM） study on the acetylating deactivation mechanism of isoniazid were presented.This type of reaction was catalyzed by arylamine N-acetyltransferases（NATs） and the results strongly support a direct acetyl group transfer process rather than a stepwise one.The isoniazid was strictly restrained in proper relative position to accept the acetyl group by a Hydrogen-bond network formed by the residues at the active center.The residues,His110 and Cys70,would be functioned as ＇general base＇ rather than ＇general acid＇.If all the residues（including H2O molecules） were removed from the system,the activation energy will be increased from 145.1 to 243.3 kJ/mol.The calculations met the experimental data with good agreement.展开更多
A new reversibly switchable fluorescent protein（RSFP）, namely Dreiklang, exhibits prominent feature that the wavelengths for switching and fluorescence are decoupled due to its great different structures between bri...A new reversibly switchable fluorescent protein（RSFP）, namely Dreiklang, exhibits prominent feature that the wavelengths for switching and fluorescence are decoupled due to its great different structures between bright and dark states. This feature might also induce some nonlinear optic（NLO） properties changing as switching between two states, which might promote new method of biological science. We employ the QM/MM method to simulate the structures of different states, and study their second harmonic generation（SHG） and two-photon absorption（TPA） properties. And we found different states of Dreiklang have different SHG and TPA responses. The SHG and TPA properties of Dreiklang are correlated to particularly geometrical structures of different states, especially the centrosymmetric or nocentrosymmetric π-stacking structures which are formed by chromophore and beside residue Tyr203, so the SHG and TPA responses could be changed as the light induces switching among different states of Dreiklang. This work would prospectively guide the application of Dreiklang on the NLO technology, and help the development of new RSFP with special NLO function.展开更多
Multi-scale quantum-mechanical/molecular-mechanical(QM/MM) and large-scale QM simulation provide valuable insight into enzyme mechanism and structure-property relationships. Analysis of the electron density afforded t...Multi-scale quantum-mechanical/molecular-mechanical(QM/MM) and large-scale QM simulation provide valuable insight into enzyme mechanism and structure-property relationships. Analysis of the electron density afforded through these methods can enhance our understanding of how the enzyme environment modulates reactivity at the enzyme active site. From this perspective, tools from conceptual density functional theory to interrogate electron densities can provide added insight into enzyme function. We recently introduced the highly parallelizable Fukui shift analysis(FSA) method, which identifies how frontier states of an active site are altered by the presence of an additional QM residue to identify when QM treatment of a residue is essential as a result of quantum-mechanically affecting the behavior of the active site. We now demonstrate and analyze distance and residue dependence of Fukui function shifts in pairs of residues representing different non-covalent interactions. We also show how the interpretation of the Fukui function as a measure of relative nucleophilicity provides insight into enzymes that carry out S_N2 methyl transfer. The FSA method represents a promising approach for the systematic, unbiased determination of quantum mechanical effects in enzymes and for other complex systems that necessitate multi-scale modeling.展开更多
With the aid of Meteorological Information Composite and Processing System (MICAPS), satellite wind vectors derived from the Geostationary Meteorological Statellite-5 (GMS-5) and retrieved by National Satellite Meteor...With the aid of Meteorological Information Composite and Processing System (MICAPS), satellite wind vectors derived from the Geostationary Meteorological Statellite-5 (GMS-5) and retrieved by National Satellite Meteorology Center of China (NSMC) can be obtained. Based on the nudging method built in the fifth-generation Mesoscale Model (MM5) of Pennsylvania State University and Na- tional Center for Atmospheric Research, a data preprocessor is developed to convert these satellite wind vectors to those with specified format required in MM5. To examine the data preprocessor and evaluate the impact of satellite winds from GMS-5 on MM5 simulations, a series of numerical experimental fore- casts consisting of four typhoon cases in 2002 are designed and implemented. The results show that the preprocessor can process satellite winds smoothly and MM5 model runs successfully with a little extra computational load during ingesting these winds, and that assimilation of satellite winds by MM5 nudging method can obviously improve typhoon track forecast but contributes a little to typhoon intensity forecast. The impact of the satellite winds depends heavily upon whether the typhoon bogussing scheme in MM5 was turned on or not. The data preprocessor developed in this paper not only can treat GMS-5 satellite winds but also has capability with little modification to process derived winds from other geostationary satellites.展开更多
The infrared （IR） spectra of the N-methylacetamide molecule in water are calculated by using the MD simulation with high-level QM]MM corrections. The B3LYP and MP2 levels with 6-31 I＋＋G＊＊ basis set are used for ...The infrared （IR） spectra of the N-methylacetamide molecule in water are calculated by using the MD simulation with high-level QM]MM corrections. The B3LYP and MP2 levels with 6-31 I＋＋G＊＊ basis set are used for the QM region, respectively, Our results show all IR spectra at the B3LYP level are well consistent with the corresponding MP2 results. A dynamical charge fluctuation is observed for each atom along the simulation trajectories due to the electrostatic polarization （EP） effects from surrounding solvent environment, We find that the QM/MM corrected IR spectra satisfactorily reprodnce the experimental vibrational features of amide 1-11I modes.展开更多
P450 cin(CYP176 A1) isolated from Citrobacter braakii is a biodegradation enzyme that catalyzes the enantiospecific conversion of 1,8-cineole to(1 R)-6β-hydroxycineole. In many P450 family members the mechanism of pr...P450 cin(CYP176 A1) isolated from Citrobacter braakii is a biodegradation enzyme that catalyzes the enantiospecific conversion of 1,8-cineole to(1 R)-6β-hydroxycineole. In many P450 family members the mechanism of proton delivery for O2activation is proposed to require a conserved acid-alcohol dyad in the active area, while P450 cin has no such residue with alcohol but asparagine instead. In the present work, the mechanism of the first proton transfer of O2activation in P450 cin has been investigated by molecular dynamics(MD) and hybrid quantum mechanics/molecular mechanics(QM/MM) techniques. The MD simulation suggests there are two hydrogen bonding networks around the active site, one involving Asp241 and the other involving Glu356. According to our MD and QM/MM calculations, this Asp241 channel is proposed to be the energy accessible. MD results show that the hydrogen bonds around the substrate may contribute to regio-and stereo-oxidation of the substrate.展开更多
The dioxygen activation catalyzed by 4-hydorxylphenyl pyruvate dioxygenase(HPPD)were reinvestigated by using hybrid quantum mechanics/molecular mechanics(QM/MM)approaches at the B3LYP/6-311++G(d,p):AMBER level.These s...The dioxygen activation catalyzed by 4-hydorxylphenyl pyruvate dioxygenase(HPPD)were reinvestigated by using hybrid quantum mechanics/molecular mechanics(QM/MM)approaches at the B3LYP/6-311++G(d,p):AMBER level.These studies showed that this reaction consisted of two steps including the dioxygen addition/decarboxylation and hetero O-O bond cleavage,where the first step was found to be rate-determining.The former step initially runs on a septet potential energy surface(PES),then switches to a quintet PES after crossing a septet/quintet minimum energy crossing point(MECP)5-7M2,whereas the rest step runs on the quintet PES.The reliability of our theoretical predictions is supported by the excellent agreement of the calculated free-energy barrier value of 16.9 kcal/mol with available experimental value of 16-17 kcal/mol.The present study challenges the widely accepted view which holds that the O2activation catalyzed byα-keto glutamate(α-KG)dioxygenase mainly runs on the quintet PES and provides new insight into the catalytic mechanism ofα-KG dioxygenase and/or other related Fe(Ⅱ)-dependent oxygenase.展开更多
采用数值模拟研究PVT法φ150 mm 4H-SiC单晶生长的功率、频率选择、坩埚位置及保温厚度等关键生长参数。研究表明φ150 mm 4H-SiC单晶生长功率是2inch 4H-SiC生长功率的2倍,优化的加热频率在5 k Hz以下,系统分析不同生长参数下生长腔内...采用数值模拟研究PVT法φ150 mm 4H-SiC单晶生长的功率、频率选择、坩埚位置及保温厚度等关键生长参数。研究表明φ150 mm 4H-SiC单晶生长功率是2inch 4H-SiC生长功率的2倍,优化的加热频率在5 k Hz以下,系统分析不同生长参数下生长腔内径向及轴向温度梯度的变化规律。在此基础上初步的进行了φ150 mm 4H-SiC单晶的生长工作,获得了无裂纹、直径完整的高质量SiC衬底材料。拉曼光谱Mapping测量显示φ150 mm SiC衬底全片无多型,均为4H-SiC晶型。X光摇摆曲线显示半宽小于30 arcsec。采用掺杂过渡金属V杂质,获得了电阻率超过5×109Ω·cm的150 mm SiC衬底。展开更多
基金Supported by the National Natural Science Foundation of China (No. 20603030 and No. 21103080)the Natural Science Foundation of Shandong Province (No. ZR2010BL023)
文摘Both a molecule dynamic study and a combined quantum mechanics and mole-cule mechanics（QM/MM） study on the acetylating deactivation mechanism of isoniazid were presented.This type of reaction was catalyzed by arylamine N-acetyltransferases（NATs） and the results strongly support a direct acetyl group transfer process rather than a stepwise one.The isoniazid was strictly restrained in proper relative position to accept the acetyl group by a Hydrogen-bond network formed by the residues at the active center.The residues,His110 and Cys70,would be functioned as ＇general base＇ rather than ＇general acid＇.If all the residues（including H2O molecules） were removed from the system,the activation energy will be increased from 145.1 to 243.3 kJ/mol.The calculations met the experimental data with good agreement.
基金based on work supported by the National Natural Science Foundation of China(No.21703246 and 21403242)Natural Science Foundation of Fujian Province(2014J05021)
文摘A new reversibly switchable fluorescent protein（RSFP）, namely Dreiklang, exhibits prominent feature that the wavelengths for switching and fluorescence are decoupled due to its great different structures between bright and dark states. This feature might also induce some nonlinear optic（NLO） properties changing as switching between two states, which might promote new method of biological science. We employ the QM/MM method to simulate the structures of different states, and study their second harmonic generation（SHG） and two-photon absorption（TPA） properties. And we found different states of Dreiklang have different SHG and TPA responses. The SHG and TPA properties of Dreiklang are correlated to particularly geometrical structures of different states, especially the centrosymmetric or nocentrosymmetric π-stacking structures which are formed by chromophore and beside residue Tyr203, so the SHG and TPA responses could be changed as the light induces switching among different states of Dreiklang. This work would prospectively guide the application of Dreiklang on the NLO technology, and help the development of new RSFP with special NLO function.
文摘Multi-scale quantum-mechanical/molecular-mechanical(QM/MM) and large-scale QM simulation provide valuable insight into enzyme mechanism and structure-property relationships. Analysis of the electron density afforded through these methods can enhance our understanding of how the enzyme environment modulates reactivity at the enzyme active site. From this perspective, tools from conceptual density functional theory to interrogate electron densities can provide added insight into enzyme function. We recently introduced the highly parallelizable Fukui shift analysis(FSA) method, which identifies how frontier states of an active site are altered by the presence of an additional QM residue to identify when QM treatment of a residue is essential as a result of quantum-mechanically affecting the behavior of the active site. We now demonstrate and analyze distance and residue dependence of Fukui function shifts in pairs of residues representing different non-covalent interactions. We also show how the interpretation of the Fukui function as a measure of relative nucleophilicity provides insight into enzymes that carry out S_N2 methyl transfer. The FSA method represents a promising approach for the systematic, unbiased determination of quantum mechanical effects in enzymes and for other complex systems that necessitate multi-scale modeling.
基金Supported by Major State Basic Research Development Program of China (973 Program, No.2005CB4223-01) and Key Technologies R & D Program of China (No.2001BA603B-01).
文摘With the aid of Meteorological Information Composite and Processing System (MICAPS), satellite wind vectors derived from the Geostationary Meteorological Statellite-5 (GMS-5) and retrieved by National Satellite Meteorology Center of China (NSMC) can be obtained. Based on the nudging method built in the fifth-generation Mesoscale Model (MM5) of Pennsylvania State University and Na- tional Center for Atmospheric Research, a data preprocessor is developed to convert these satellite wind vectors to those with specified format required in MM5. To examine the data preprocessor and evaluate the impact of satellite winds from GMS-5 on MM5 simulations, a series of numerical experimental fore- casts consisting of four typhoon cases in 2002 are designed and implemented. The results show that the preprocessor can process satellite winds smoothly and MM5 model runs successfully with a little extra computational load during ingesting these winds, and that assimilation of satellite winds by MM5 nudging method can obviously improve typhoon track forecast but contributes a little to typhoon intensity forecast. The impact of the satellite winds depends heavily upon whether the typhoon bogussing scheme in MM5 was turned on or not. The data preprocessor developed in this paper not only can treat GMS-5 satellite winds but also has capability with little modification to process derived winds from other geostationary satellites.
基金supported by the Natural Science Foundation of China(Nos.21306070 and 20966003)the Science&Technology Programs of Education Department of Jiangxi Province(No.GJJ12191)
文摘The infrared （IR） spectra of the N-methylacetamide molecule in water are calculated by using the MD simulation with high-level QM]MM corrections. The B3LYP and MP2 levels with 6-31 I＋＋G＊＊ basis set are used for the QM region, respectively, Our results show all IR spectra at the B3LYP level are well consistent with the corresponding MP2 results. A dynamical charge fluctuation is observed for each atom along the simulation trajectories due to the electrostatic polarization （EP） effects from surrounding solvent environment, We find that the QM/MM corrected IR spectra satisfactorily reprodnce the experimental vibrational features of amide 1-11I modes.
基金supported by the National Natural Science Foundation of China(No.21573237,21603227,21403242,21703246)the Natural Science Foundation of Fujian Province(2017J05032)
文摘P450 cin(CYP176 A1) isolated from Citrobacter braakii is a biodegradation enzyme that catalyzes the enantiospecific conversion of 1,8-cineole to(1 R)-6β-hydroxycineole. In many P450 family members the mechanism of proton delivery for O2activation is proposed to require a conserved acid-alcohol dyad in the active area, while P450 cin has no such residue with alcohol but asparagine instead. In the present work, the mechanism of the first proton transfer of O2activation in P450 cin has been investigated by molecular dynamics(MD) and hybrid quantum mechanics/molecular mechanics(QM/MM) techniques. The MD simulation suggests there are two hydrogen bonding networks around the active site, one involving Asp241 and the other involving Glu356. According to our MD and QM/MM calculations, this Asp241 channel is proposed to be the energy accessible. MD results show that the hydrogen bonds around the substrate may contribute to regio-and stereo-oxidation of the substrate.
基金supported by the National Science Foundation(Grant number:0817940to HG)the DOE Office of Biological and Environmental Research-Genome to Life Program through the BioEnergy Science Center(BESC)(to FC)+2 种基金the Sun Grant Initiative(to FC)the computer resources(Newton)from University of Tennessee Knoxvillethe NSF TeraGrid resources provided by the University of Texas at Austin
基金supported by the National Key R&D Program(No.2021YFD1700100)National Natural Science Foundation of China(Nos.21837001,21273089)+2 种基金the Open Project Fund of the Key Laboratory of the Pesticides and Chemical Biology of Central China Normal University(No.2018-A01)the Fundamental Research Funds for the Central Universitiesthe Fundamental Research Funds for the South-Central University for Nationalities(No.CZW20020)。
文摘The dioxygen activation catalyzed by 4-hydorxylphenyl pyruvate dioxygenase(HPPD)were reinvestigated by using hybrid quantum mechanics/molecular mechanics(QM/MM)approaches at the B3LYP/6-311++G(d,p):AMBER level.These studies showed that this reaction consisted of two steps including the dioxygen addition/decarboxylation and hetero O-O bond cleavage,where the first step was found to be rate-determining.The former step initially runs on a septet potential energy surface(PES),then switches to a quintet PES after crossing a septet/quintet minimum energy crossing point(MECP)5-7M2,whereas the rest step runs on the quintet PES.The reliability of our theoretical predictions is supported by the excellent agreement of the calculated free-energy barrier value of 16.9 kcal/mol with available experimental value of 16-17 kcal/mol.The present study challenges the widely accepted view which holds that the O2activation catalyzed byα-keto glutamate(α-KG)dioxygenase mainly runs on the quintet PES and provides new insight into the catalytic mechanism ofα-KG dioxygenase and/or other related Fe(Ⅱ)-dependent oxygenase.
文摘采用数值模拟研究PVT法φ150 mm 4H-SiC单晶生长的功率、频率选择、坩埚位置及保温厚度等关键生长参数。研究表明φ150 mm 4H-SiC单晶生长功率是2inch 4H-SiC生长功率的2倍,优化的加热频率在5 k Hz以下,系统分析不同生长参数下生长腔内径向及轴向温度梯度的变化规律。在此基础上初步的进行了φ150 mm 4H-SiC单晶的生长工作,获得了无裂纹、直径完整的高质量SiC衬底材料。拉曼光谱Mapping测量显示φ150 mm SiC衬底全片无多型,均为4H-SiC晶型。X光摇摆曲线显示半宽小于30 arcsec。采用掺杂过渡金属V杂质,获得了电阻率超过5×109Ω·cm的150 mm SiC衬底。
