Quantifying Electronic Effects in QM and QM/MM Biomolecular Modeling with the Fukui Function

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.

Nonlinear wave dispersion in monoatomic chains with lumped and distributed masses:discrete and continuum models

The main objective of this paper is to investigate the influence of inertia of nonlinear springs on the dispersion behavior of discrete monoatomic chains with lumped and distributed masses.The developed model can represent the wave propagation problem in a non-homogeneous material consisting of heavy inclusions embedded in a matrix.The inclusions are idealized by lumped masses,and the matrix between adjacent inclusions is modeled by a nonlinear spring with distributed masses.Additionally,the model is capable of depicting the wave propagation in bi-material bars,wherein the first material is represented by a rigid particle and the second one is represented by a nonlinear spring with distributed masses.The discrete model of the nonlinear monoatomic chain with lumped and distributed masses is first considered,and a closed-form expression of the dispersion relation is obtained by the second-order Lindstedt-Poincare method(LPM).Next,a continuum model for the nonlinear monoatomic chain is derived directly from its discrete lattice model by a suitable continualization technique.The subsequent use of the second-order method of multiple scales(MMS)facilitates the derivation of the corresponding nonlinear dispersion relation in a closed form.The novelties of the present study consist of(i)considering the inertia of nonlinear springs on the dispersion behavior of the discrete mass-spring chains;(ii)developing the second-order LPM for the wave propagation in the discrete chains;and(iii)deriving a continuum model for the nonlinear monoatomic chains with lumped and distributed masses.Finally,a parametric study is conducted to examine the effects of the design parameters and the distributed spring mass on the nonlinear dispersion relations and phase velocities obtained from both the discrete and continuum models.These parameters include the ratio of the spring mass to the lumped mass,the nonlinear stiffness coefficient of the spring,and the wave amplitude.

A unified Minorization-Maximization approach for estimation of general mixture models

The mixed distribution model is often used to extract information from heteroge-neous data and perform modeling analysis.When the density function of mixed distribution is complicated or the variable dimension is high,it usually brings challenges to the parameter es-timation of the mixed distribution model.The application of MM algorithm can avoid complex expectation calculations,and can also solve the problem of high-dimensional optimization by decomposing the objective function.In this paper,MM algorithm is applied to the parameter estimation problem of mixed distribution model.The method of assembly and decomposition is used to construct the substitute function with separable parameters,which avoids the problems of complex expectation calculations and the inversion of high-dimensional matrices.

QM/MM方法的研究

从理论上探讨了QM/MM方法在模拟计算生物大分子体系的运用,实践表明这种方法能提高计算结果的精确性,能有效地降低计算成本.

HIV-1蛋白酶与抑制剂结合中桥接水分子作用的QM/MM研究

对HIV-1蛋白酶与抑制剂2AH和4AH结合的两个复合物体系进行了水溶液环境下量子力学分子力学混合方法(hybrid QM/MM)的1ns分子动力学模拟,用MM-GBSA方法得到桥接水分子W301与HIV-1蛋白酶和抑制剂结合体的结合自由能分别为-24.93 kJ/mol和-20.29 kJ/mol,表明W301在抑制剂和HIV-1蛋白酶结合的过程中起到了不能被忽略的作用。

W301水分子在HIV-1蛋白酶和配体ABT-538结合中作用的QM/MM研究

结晶水分子W301在几乎所有的HIV-1蛋白酶(HIV-1PR)和配体的晶体结构中出现.在HIV-1PR中A链天门冬氨酸残基Asp25质子化状态或B链Asp25质子化状态下,QM/MM模拟后MM-GBSA方法计算得到W301水分子在HIV-1PR/ABT-538结合中的自由能贡献分别为-16.88kJ/mol、-17.63kJ/mol,W301水分子在HIV-1PR/ABT-538的结合中起到了关键的作用.进一步分析发现W301水分子与HIV-1PR和ABT-538分别形成了两个、四个氢键.

丝组二肽对DNA切割作用的QM-MM研究

运用QM MM方法对丝组二肽切割DNA作用的机理进行了研究 .通过计算得到了丝组二肽与DNA形成多氢键作用的有效分子识别模型及相关分子结构参数 ,从理论上解释了丝组二肽与DNA通过形成五配位磷中间体而使磷酸二酯键发生水解 ,从而使得DNA被切断的作用机理 .

烟酰胺酶催化水解脱氨反应的QM/MM分子动力学模拟

采用QM(PM3)/MM分子动力学(MD)方法模拟了烟酰胺酶催化烟酰胺水解脱氨形成烟碱酸的反应过程.计算结果表明,硫的亲核进攻是整个反应的速率控制步骤.当改变Ala155所在Loop区的位置,在亲核进攻时,底物能够自由旋转,可以加速亲核进攻过程并降低整个催化反应的能垒.讨论了氨分子的离去过程和质子传递过程的相关细节.为烟酰胺酶的定点突变以及脱氨酶的设计提供了有益的参考.

t/k-fault diagnosis algorithm of n-dimensional hypercube network based on the MM*model

Compared with accurate diagnosis, the system’s selfdiagnosing capability can be greatly increased through the t/kdiagnosis strategy at most k vertexes to be mistakenly identified as faulty under the comparison model, where k is typically a small number. Based on the Preparata, Metze, and Chien(PMC)model, the n-dimensional hypercube network is proved to be t/kdiagnosable. In this paper, based on the Maeng and Malek(MM)*model, a novel t/k-fault diagnosis(1≤k≤4) algorithm of ndimensional hypercube, called t/k-MM*-DIAG, is proposed to isolate all faulty processors within the set of nodes, among which the number of fault-free nodes identified wrongly as faulty is at most k. The time complexity in our algorithm is only O(2~n n~2).

High-resolution modeling and evaluation of ozone air quality of Osaka using MM5-CMAQ system

High-resolution modeling approach is increasingly being considered as a necessary step for improving the monitoring and predictions of regional air quality. This is especially true for highly urbanized region with complex terrain and land-use. This study uses Community Multiscale Air Quality （CMAQ） model coupled with MM5 mesoscale model for a comprehensive analysis to assess the suitability of such high-resolution modeling system in predicting ozone air quality in the complex terrains of Osaka, Japan. The 1-km and 3-kin grid domains were nested inside a 9-km domain and the domain with 1-km grid covered the Osaka region. High-resolution Grid Point Value-Mesoscale Model （GPV-MSM） data were used after suitable validation. The simulated ozone concentrations were validated and evaluated using statistical metrics using performance criteria set for ozone. Daily maxima of ozone were found better simulated by the 1-krn grid domain than the coarser 9-km and 3-km domains, with the maximum improvement in the mean absolute gross error about 3 ppbv. In addition, 1-km grid results fared better than other grids at most of the observation stations that showed noticeable differences in gross error as well as correlation. These results amply justify the use of the integrated high-resolution MM5-CMAQ modeling system in the highly urbanized region, such as the Osaka region, which has complex terrain and land-use.

CO分子在肌红蛋白结合口袋的QM／MM动力学模拟

肌红蛋白具有存储和运输人体内双原子小分子的重要生物学功能．实验证实CO在靠近肌红蛋白血红素基团边缘的结合口袋中具有两个不同的方向．在本文中，我们基于从头算QM／MM动力学模拟的方法详细研究了这两个状态（这两种状态分别命名为B1和B2态）．通过与实验测量的红外光谱数据的对比，证实B1和B2态分别对应于Fe…CO（碳原子更加靠近血红素的中心铁原子）和Fe…OC（氧原子更加靠近血红素的中心铁原子），由蛋白以及溶剂对一氧化碳分子造成的量子极化效应是一氧化碳能够稳定持有两个不同状态的主要源动力．我们计算得到的两个不同状态之间的振动频率偏移量为13．1cm-1，与实验测得的11．5cm-1的位移吻合的很好．模拟结果揭示出蛋白周围的溶剂水可以通过在蛋白活性区域施加电场的方式来辅助加强蛋白的生物功能．通过对肌红蛋白每个残基在一氧化碳分子中心位置产生的电场的定量计算，发现了对总电场有较大贡献的一些氨基酸残基，其中包括了一些带电残基以及三个非带电残基（即HIS64，ILE107，和PHE43）．

An evaporation duct prediction model coupled with the MM5

Evaporation duct is an abnormal refractive phenomenon in the marine atmosphere boundary layer. It has been generally accepted that the evaporation duct prominently affects the performance of the electronic equipment over the sea because of its wide distribution and frequent occurrence. It has become a research focus of the navies all over the world. At present, the diagnostic models of the evaporation duct are all based on the Monin-Obukhov similarity theory, with only differences in the flux and character scale calculations in the surface layer. These models are applicable to the stationary and uniform open sea areas without considering the alongshore effect. This paper introduces the nonlinear factor a and the gust wind item wg into the Babin model, and thus extends the evaporation duct diagnostic model to the offshore area under extremely low wind speed. In addition, an evaporation duct prediction model is designed and coupled with the fifth generation mesoscale model （MMS）. The tower observational data and radar data at the Pingtan island of Fujian Province on May 25-26, 2002 were used to validate the forecast results. The outputs of the prediction model agree with the observations from 0 to 48 h. The relative error of the predicted evaporation duct height is 19.3% and the prediction results are consistent with the radar detection.

QM/MM and MD Studies of the First Proton Transfer for O2 Activation in the Catalytic Cycle of Cytochrome P450cin

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.

QM/MM Study of the Second Harmonic Generation and Two-photon Absorption Properties of a Fluorescent Proteins-Dreiklang

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.

Molecular Dynamics and Combined QM/MM Studies on the Deactivation of anti-Tubercular Drug Isoniazid by Arylamine N-Acetyltransferases

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.

MM CALCULATIONS OF THE METAL-PROTEIN MODEL COMPLEXES Ⅰ.MOLECULAR FORCE FIELD FOR COBALT COMPEXES

Cobalt-protein complexes play an important role in biochemical processes.The structure of the model molecule,Co(H_2O)_3SO_4(phen) has been studied by molecular mechanics.The molecular force field (MM2) parameters have been developed for the particular class of the complexes.

基于MMS模型的继电保护装置自动测试技术研究

提出一种基于MMS模型的继电保护装置自动测试技术,该技术能够自动模拟继电保护装置的输入信息,自动验证输出信息,通过MMS报文读写保护装置的定值、控制字、软压板,针对各厂家“六统一”保护型号功能配置,建立典型测试模板库,实现继电保护装置一键式测试,并通过中间模型文件解决了不同厂家的保护装置数据输出端口信息描述不统一的问题,实现模型自动映射。最后以某型号线路保护装置测试为例验证所提方法的可行性。

Models3在北京地区PM_(10)模拟应用中的三维系统检验

为研究北京地区大气PM10的变化规律和三维空间结构,文章基于Models3/CMAQ空气质量模式,利用北京及周边省市详细调查的污染源数据,采取双层网格嵌套技术建立起适用于北京及周边地区的大气PM10数值模拟系统。为了检验该模式系统的准确性和可靠性,文章将模拟结果与北京市城近郊区7个地面站近2500h的逐时地面监测数据以及一次典型污染过程的激光雷达垂直观测记录分别进行了对比分析,结果表明,该模式系统较好的反映了北京地区PM10浓度三维时空分布特征,是研究华北地区复杂地形下大气PM10传输及演变规律的一个有效工具。

300mm硅片双面抛光过程数学模拟及分析

建立了双面抛光过程中硅片表面上的一点相对于抛光布的运动模型;利用数学软件,模拟出不同速度下的运动轨迹。轨迹和实验结果表明,在其他双面抛光工艺不变的情况下,改变抛光机四个部分的转速,对硅片表面的平整度有很大的影响,特别是边缘部分的局部平整度。优化四个转速,可以显著改善300mm硅片表面的平整度和局部平整度。

150mm×150mm方坯连铸高效化的二冷技术

根据连铸坯二冷均匀冷却的构想 ,重新设计并优化二冷喷淋结构和喷嘴的布置 ,增加了一个二冷喷啉段。提出二冷段各段水量Qi(L min)与钢液过热度ΔT(℃ )和拉速V(m min)关系的新的二冷水模型 :Qi=a +bv +cv2 +d(ΔT - 30 ) +F ,其中a、b、c、d和F为常数。实践证明 ,通过使用优化后的二冷结构和模型 ,15 0mm× 15 0mm连铸坯断面的最高拉速达 3 8～ 4 0m min ,Q2 35和HRB335钢连铸坯的质量明显改善 ,疏松、偏析、裂纹等低倍组织≤ 2级 ,废品率降低 0 2 3个百分点 ,钢坯平均日产量由 8 0万t提高至 9 4万t,生产率提高约 17 5 %。