量子力学和分子力学组合方法

量子力学和分子力学(QM/MM)组合方法结合了量子力学的精确性和分子力学的高效性,在研究凝聚态中的化学反应及生物大分子的结构和活性等方面发挥着重要作用。本文主要介绍了QM/MM组合方法的基本原理及国内外有关QM/MM组合方法的研究进展。     

Enantioselective Synthesis of Macrocyclic Heterobiaryl Derivatives of Molecular Asymmetry by Molybdenum‐Catalyzed Asymmetric Ring‐Closing Metathesis

Winding vine‐shaped molecular asymmetry is induced by enantioselective ring‐closing metathesis with a chiral molybdenum catalyst. The reaction proceeds under mild conditions through an E‐selective ring‐closing metathesis leading to macrocyclic bisazoles with enantioselectivities of up to 96 % ee.     

X-ray Crystal Structure and Molecular Mechanics Calculations of (2,6-iso-dipropyl-phcnylamidc) Dimethyl (tetra-methylecyclopenta- dienyl)Silane Titanium Dichloride

ExperimentalSynthesisofitToI.sg(4mmol.)TiCI,.THFin25mLTHFwasaddedI.sg(4mmol.)dilithium(2,6-propylphenylamide)dimethyl(tetra-methylcyclopentadienyl)silaneandthemixturewasallowedtostirforIhour,then0.639AgCI(4mmol.)wasadded.After4hoursstirring,thesolventwasmovedandtheresiduewasextractedwithdiethylether.Theetherextractwasfilteredandevaporatedtodrynesstogive0.409yellowcrystallinesolid,yield41%.'H-NMR(C,D,)f0.48(6H),l.I2(6H),l.49(6H),l.98(6H).2.18(6H),and3.04(2H).Asuitablesinglecrystalwa…     

Stereodivergent Anion Binding Catalysis with Molecular Motors

A photoresponsive chiral catalyst based on an oligotriazole‐functionalized unidirectional molecular motor has been developed for stereodivergent anion binding catalysis. The motor function controls the helical chirality of supramolecular assemblies with chloride anions, which by means of chirality transfer enables the enantioselective addition of a silyl ketene acetal nucleophile to oxocarbenium cations. Reversal of stereoselectivity (up to 142 % Δee) was achieved through rotation of the motor core induced by photochemical and thermal isomerization steps.     

A Molecular Mechanics Energy Partitioning Software for Biomolecular Systems

The partitioning of the molecular mechanics (MM) energy in calculations involving biomolecular systems is important to identify the source of major stabilizing interactions, e.g., in ligand–protein interactions, or to identify residues with considerable contributions in hybrid multiscale calculations, i.e., quantum mechanics/molecular mechanics (QM/MM). Here, we describe Energy Split, a software program to calculate MM energy partitioning considering the AMBER Hamiltonian and parameters. Energy Split includes a graphical interface plugin for VMD to facilitate the selection of atoms and molecules belonging to each part of the system. Energy Split is freely available at or can be easily installed through the VMD Store.     

Quantum Mechanics/Molecular Mechanics Studies on the Mechanism of Action of Cofactor Pyridoxal 5′‐Phosphate in Ornithine 4,5‐Aminomutase

A computational study was performed on the experimentally elusive cyclisation step in the cofactor pyridoxal 5′‐phosphate (PLP)‐dependent D ‐ornithine 4,5‐aminomutase (OAM)‐catalysed reaction. Calculations using both model systems and a combined quantum mechanics/molecular mechanics approach suggest that regulation of the cyclic radical intermediate is achieved through the synergy of the intrinsic catalytic power of cofactor PLP and the active site of the enzyme. The captodative effect of PLP is balanced by an enzyme active site that controls the deprotonation of both the pyridine nitrogen atom (N1) and the Schiff‐base nitrogen atom (N2). Furthermore, electrostatic interactions between the terminal carboxylate and amino groups of the substrate and Arg297 and Glu81 impose substantial “strain” energy on the orientation of the cyclic intermediate to control its trajectory. In addition the “strain” energy, which appears to be sensitive to both the number of carbon atoms in the substrate/analogue and the position of the radical intermediates, may play a key role in controlling the transition of the enzyme from the closed to the open state. Our results provide new insights into several aspects of the radical mechanism in aminomutase catalysis and broaden our understanding of cofactor PLP‐dependent reactions.     

X-ray Crystal Structure and Molecular Mechanics Calculations of (2,6-iso-dipropyl-phenylamide) Dimethyl ( tetra-methylcyclopenta-dienyl ) Silane Titanium Dichloride

Crystal and molecular structure of (2,6-dipropylphenylamide) dimethyl (tetra-methyl cyclopentadienyl) silane titanium dichloride (I) was fully characterized by X-ray diffraction. The crystal is obtained from a mixture of ether/hexane as orthorhombic, with a = 12.658 (3) (A), b = 16.62 (3)(A), c = 11.760 (2)(A), V = 2474.2 (9)(A) 3, Z = 4, space group Pnma, R = 0.0399. Componud I compose of the π-bounded ring with its dimethylsilyl-dipropyl phenyl amido group and the two terminal chloride atoms coordinated to central metal to form a so-called constrained geometry catalyst (CGC) structure. The result of molecular mechanics (MM) calculations on compound I shows that bond lengths and bond angles from the MM calculation are comparable to the data obtained from the X-ray diffraction study. The relation of the structure of CGCs and their catalytic activity by MM calculations is also discussed.     

杯芳烃构象的分子力学研究

杯芳烃是对位取代的苯酚与甲醛反应得到的环状缩合物,由于其独特的结构和易于衍生化的特点而受到广泛的关注［１］．杯芳烃中苯酚单元由亚甲基相连,由于酚羟基端可经杯中央翻转而产生多种构象异构体．杯［４］芳烃有４种典型构象：杯式、部分杯式、１,２－交替式和１,...     

Quantum Mechanics/Molecular Mechanics Studies of the Mechanism of Cysteine Proteases Inhibition by Dipeptidyl Nitroalkenes

In this work a computational study of the mechanism of inhibition of cruzain, rhodesain, and cathepsin L cysteine proteases by the dipeptidyl nitroalkene Cbz-Phe-Ala-CH=CH-NO₂ has been carried out by means of molecular dynamics simulations with hybrid QM/MM potentials. The free-energy surfaces confirmed that the inhibition takes place by the formation of a covalent bond between the protein and the β-carbon atom of the inhibitor. According to the results, the tested inhibitor should be a much more efficient inhibitor of cruzain than of rhodesain, and little activity would be expected against cathepsin L, in total correspondence with the available experimental data. The origin of these differences may lie in the different stabilizing electrostatic interactions established between the inhibitor and the residues of the active site and S2 pocket of these enzymes. These results may be useful for the rational design of new dipeptidyl nitroalkenes with higher and more selective inhibitory activity against cysteine proteases.     

分子力学在有机化学中的应用

本文评述了近年来分子力学在有机化学中的应用,特别是在有机化学反应和核磁共振中的应用。     

分子筛上手性催化的模拟计算

本文应用分子模拟途径研究了系列反应物丙烯基羟基乙烯酮二硫代乙缩醛在有、无分子筛催化条件下Ｔｈｉｏ－Ｃｌａｉｓｅｎ重排。我们证实Ｓｒｅｅｋｕｍａｒ等人实验在有、无分子筛催化条件下的Ｔｈｉｏ－Ｃｌａｉｓｅｎ重排结果可分别通过分子筛－分应物之间相互作用的能学和反应物的空间能计算得到合理解释。本文的方法能成功地识别一个给定Ｔｈｉｏ－Ｃｌａｉｓｅｎ重排在有、无分子筛催化条件下的优化产物。     

Delft Molecular Mechanics Study on the Structures of Monoclinic MF Iand H[ Al] ZSM-5

１　ＩＮＴＲＯＤＵＣＴＩＯＮＺｅｏｌｉｔｅｓ，ａｎｅｘｔｒａｏｒｄｉｎａｒｙｃｌａｓｓｏｆａｄｖａｎｃｅｄｉｎｏｒｇａｎｉｃｍａｔｅｒｉａｌｓ，ａｒｅａｔｔｒａｃｔｉｎｇｉｎｃｒｅａｓｉｎｇａｔｔｅｎｔｉｏｎｏｗｉｎｇｔｏｔｈｅｉｒｉｏｎｅｘｃｈａｎｇｅ，ｍｏｌｅｃｕｌａｒｓｉｅｖｉｎｇａｎｄｓｈａｐｅｓｅｌｅｃｔｉｖｅｃａｔａｌｙｔｉｃｐｒｏｐｅｒｔｉｅｓ．ＴｈｅｍｅｄｉｕｍｐｏｒｅｚｅｏｌｉｔｅｓｐｒｅｓｅｎｔｉｎｇｔｈｅＭＦＩｔｏｐｏｌｏｇｙ（ｓｉｌｉｃａｌｉｔｅ，ＺＳＭ５ａｎｄ…     

NMR和分子力学法研究溶液中有机分子结构

在分子力学能量优化项中加入由ＮＭＲ实验得到的几何参数二面角（相应于~３Ｊ_（ＨＨ）耦合常数）及质子间距所构造的约束函数，使分子力学计算得到的能量极小点的分子构象，其耦合常数（~３Ｊ_（ＨＨ））及质子间距同ＮＭＲ实验结果相符合。文中以（±）－３－（４＇－甲苯基）－１－氮杂双环［２．２．２］－３－辛醇为例，采用自编的ＮＭＲ参数约束的分子力学计算程序ＭＭ２ＮＪ对其构象进行了计算。所得结果与Ｘ射线衍射法比较，有较好的一致性     

在微机上实现分子力学模拟B-DNA

DNA是典型的螺旋结构，关于它的模拟方法有很多种，本文将探讨一种能在微机上用分子力学模拟B型DNA的方法，该方法以Cs Chem3D软件包中MM2为支持力场，搭建和几何优化B－DNA，并对模拟B－DNA的构象特征进行详细分析以证实此方法的可行性。     

A Study of a Molecular Mechanics Field Used in Simulating Enantiorecognition

Enantiorecognitionisameasureofthediscriminationabilitybetweenenantiomericmolecules.Itisoffundamentalsignificanceinmanyareasofthechemicalandbiologicalsciences,italsoplaysanimportantroleinseparationofenantiomersbychromatography.Althoughtheintermolecularforces(hydrogenbonding,multipolarassociation,dispersionforces,chargetransfercomplexation,hydrophobicassociation.etc.)havebeenthoroughlystudiedandarewelldocumented,buthowtheseforcespreciselyworkinconcerttopromoteintermolecularactionisnotclearyet'.T…     

分子力学计算的参数化过程

介绍了如何通过设计模型分子构造参数的方法和过程：首先设计模型分子；在平衡位置附近选择几个点，对模型分子进行分子力学和量子化学的计算；计算出量子化学能量Eqm和分子力学能量Emm的差值；然后对结构参数（健长，键角，二面角）和能量差值进行拟合，得拟合曲线的方程，从方程的系数可求出参数．文章给出了一些实例．     

Theoretical Consideration of the External Donor of Heterogeneous Ziegler–Natta Catalysts Using Molecular Mechanics,Molecular Dynamics,and QSAR Analysis

In the previous paper we calculated the most stable structure of the catalyst and cocatalyst of metallocene catalyst systems using molecular dynamics and molecular mechanics. In this paper we postulate the active site of the heterogeneous Ziegler–Natta catalyst, and analyze it by the same methods to clarify the main factors that control the activity and molecular weight distribution of the heterogeneous catalyst systems. The roles of the external donor were also considered, and we found that the interaction energy between an external donor and the active site of the catalyst, as well as the structural factors of the external donor itself, are strongly related to both activity and molecular weight distribution. These results reveal that molecular dynamics and molecular mechanics calculations are also effective methods to screen the heterogeneous catalyst systems.     

二维分子的原子不对称性研究

基于分子形状的二进制编码提出了权原子和法来描述原子的不对称环境, 其中权原子和是以相反的方向环绕分子所得原子不对称环境的量度, 分子中一个原子的权原子和与其镜像分子中相应原子的权原子和的大小相等, 符号相反. 权原子和不仅适用于手性分子, 还能描述非手性分子中原子的不对称性. 与Randic′提出的原子和进行比较表明, 权原子和比原子和具有更好地区分能力, 因此, 权原子和能够更好地表征原子的不对称性.     

Quantum Mechanics/Molecular Mechanics Simulations Show Saccharide Distortion is Required for Reaction in Hen Egg-White Lysozyme

Hybrid quantum mechanics/molecular mechanics (QM/MM) calculations on lysozyme show significant distortion of the bound saccharide is required to facilitate the catalytic reaction.