Conformational analysis of six- and twelve-membered ring compounds by molecular dynamics

A molecular dynamics (MD)-based conformational analysis has been performed on a number of cycloalkanes in order to demonstrate the reliability and generality of MD as a tool for conformational analysis. MD simulations on cyclohexane and a series of methyl-substituted cyclohexanes were performed at temperatures between 400 and 1200 K. Depending on the simulation temperature, different types of interconversions (twist-boat–twist-boat, twist- boat–chair and chair–chair) could be observed, and the MD simulations demonstrated the expected correlation between simulation temperature and ring inversion barriers. A series of methyl-substituted 1,3- dioxanes were investigated at 1000 K, and the number of chair–chair interconversions could be quantitatively correlated to the experimentally determined ring inversion barrier. Similarly, the distribution of sampled minimum-energy conformations correlated with the energy-derived Boltzmann distribution. The macrocyclic ring system cyclododecane was subjected to an MD simulation at 1000 K and 71 different conformations could be sampled. These conformations were compared with the results of previously reported conformational analyses using stochastic search methods, and the MD method provided 19 out of the 20 most stable conformations found in the MM2 force field. Finally, the general performance of the MD method for conformational analysis is discussed.     

Time-efficient flexible superposition of medium-sized molecules

We present an efficient algorithm for the structural alignment of medium-sized organic molecules. The algorithm has been developed for applications in 3D QSAR and in receptor modeling. The method assumes one of the molecules, the reference ligand, to be presented in the conformation that it adopts inside the receptor pocket. The second molecule, the test ligand, is considered to be flexible, and is assumed to be given in an arbitrary low-energy conformation. Ligand flexibility is modeled by decomposing the test ligand into molecular fragments, such that ring systems are completely contained in a single fragment. Conformations of fragments and torsional angles of single bonds are taken from a small finite set, which depends on the fragment and bond, respectively. The algorithm superimposes a distinguished base fragment of the test ligand onto a suitable region of the reference ligand and then attaches the remaining fragments of the test ligand in a step-by-step fashion. During this process, a scoring function is optimized that encompasses bonding terms and terms accounting for steric overlap as well as for similarity of chemical properties of both ligands. The algorithm has been implemented in the FLEXS system. To validate the quality of the produced results, we have selected a number of examples for which the mutual superposition of two ligands is experimentally given by the comparison of the binding geometries known from the crystal structures of their corresponding protein–ligand complexes. On more than two-thirds of the test examples the algorithm produces rms deviations of the predicted versus the observed conformation of the test ligand below 1.5 Å. The run time of the algorithm on a single problem instance is a few minutes on a common-day workstation. The overall goal of this research is to drastically reduce run times, while limiting the inaccuracies of the model and the computation to a tolerable level.     

温和条件下环己烷的均相催化氧化

温和条件下环己烷的均相催化氧化吴泽彪，张铭俊，奚祖威（中国科学院大连化学物理研究所，大连１１６０２３）关键词环己烷，氧化，均相催化．１．前言饱和烃的氧化是很多化学家都感兴趣的一个前沿性课题．强共价Ｃ─Ｈ键由于键能大，若进行剧烈氧化则产物选择性较差，氧...     

金属次卟啉二甲酯对空气氧化环己烷的催化作用

在无任何外加溶剂及共还原剂的条件下, 将金属次卟啉二甲酯应用于催化空气氧化环己烷的氧化反应. 结果表明, 金属次卟啉二甲酯能够很好地催化环己烷的氧化反应, 与简单的金属四苯基卟啉相比, 金属次卟啉二甲酯催化剂具有更高的催化活性. 进而研究了络合金属对其催化性能的影响.     

环己烷氧化微孔催化剂的研究进展

环己烷氧化是化工生产中的重要反应之一,其氧化产物为重要的化工生产中间体,因此开发高效的环己烷氧化多相催化剂体系具有重要的理论意义和应用前景。本文综述了国内外环己烷选择氧化微孔催化剂的研究进展,分别对Y沸石、ZSM-5沸石及MOFs三大类微孔催化剂体系的组成及催化性能进行了介绍,最后展望了环己烷多相催化体系的发展趋势。     

Ewald summation and multiple time step methods for molecular dynamics simulation of biological molecules

Methods by which to determine conditions for a molecular dynamics (MD) simulation of biological molecules were investigated. Derivation of the optimal parameters of the Ewald summation was described so as to give same precision to the real space, the reciprocal space summations and the van der Waals interaction. Later, the procedure by which to determine the condition of the multiple time step method by RESPA (REference System Propagator Algorithm; Tuckerman et al., 1992, J. Chem. Phys., 97, 1990) was described as exemplified by MD simulations of a solvated β-sheet peptide. The conservation of the total energy in a microcanonical ensemble was measured to investigate the stability of the simulation conditions. The most feasible respective combinations of the time steps were: 0.25 fs for bond, angle and torsion interactions; 2 fs for van der Waals interaction and Ewald real-space summation; and 4 fs for Ewald reciprocal-space summation. Though it retained an acceptable accuracy, this condition accelerated the simulation ten-fold compared to that in which a simple velocity-Verlet method with a time step of 0.25 fs was used. The update of the correction term due to excluded neighbors was then investigated. Better results were obtained when the correction was updated with the real-space than when it was updated with the reciprocal-space summation. Finally, an MD simulation as long as 50 ps performed under the optimal Ewald and RESPA parameters was thus determined. The trajectory showed a good stability, indicating the feasibility of the parameters.     

Internal dynamics of simple floppy molecules

The dynamical behavior of simple nonrigid molecules still attracts much interest both from experimentalists and theoreticians. On the one hand, modern laser-spectroscopic techniques like SEP allow for the detection of highly excited vibrational–rotational states of a molecule, and advanced theoretical methods, on the other hand, are more and more able to calculate accurate potential energy surfaces and to simulate the intramolecular dynamics. The aim of the present article was to contribute to the understanding of the dynamical properties of simple floppy molecules by means of a comparative study of the two triatomics HCN and HO₂. Continuing our earlier work, we start from an analysis of the potential energy surface topography, then we investigate the classical dynamical behavior and the localization of the quantum states. Several conclusions of probably more general validity are drawn. © 1994 John Wiley & Sons, Inc.     

环己烷的热裂解机理

用Gaussian 98程序包中AM1法和DFT方法,对液相沉积法制碳/碳（C/C）复合材料的碳源化合物环己烷的热解机理做了量子化学理论研究.通过对化合物6种可能的热裂解路径的热力学和动力学计算,找到了环己烷热裂解的主反应路径.结果表明：(1) AM1与DFT计算均显示,断裂C－C键,最终生成乙烯和2 丁烯的反应通道是环己烷的主要裂解通道,与质谱数据吻合; (2) 除主反应路径外,余下的由易到难生成化合物的顺序为甲基环戊烷 >环己烯 >4 甲基环戊烯 >1,3 丁二烯; (3) AM1方法可以很好地推测较大分子体系的热裂解机理,而DFT方法计算的热力学量更接近实验数据.     

A Novel Type of Liquid Crystals Based on Axially Fluorinated Cyclohexane Units

Decidedly higher clearing temperatures and often also broader mesophases are exhibited by axially fluorinated cyclohexane derivatives 1 and 2 relative to their nonfluorinated analogues. A convenient method for the multigram synthesis of 1 and 2 , which represent a promising new type of liquid crystals with positive or negative dielectric anisotropy, is presented.     

Identification of possible siRNA molecules for TDP43 mutants causing amyotrophic lateral sclerosis: In silico design and molecular dynamics study

The DNA binding protein, TDP43 is a major protein involved in amyotrophic lateral sclerosis and other neurological disorders such as frontotemporal dementia, Alzheimer disease, etc. In the present study, we have designed possible siRNAs for the glycine rich region of tardbp mutants causing ALS disorder based on a systematic theoretical approach including (i) identification of respective codons for all mutants (reported at the protein level) based on both minimum free energy and probabilistic approaches, (ii) rational design of siRNA, (iii) secondary structure analysis for the target accessibility of siRNA, (iii) determination of the ability of siRNA to interact with mRNA and the formation/stability of duplex via molecular dynamics study for a period of 15 ns and (iv) characterization of mRNA–siRNA duplex stability based on thermo-physical analysis. The stable GC-rich siRNA expressed strong binding affinity towards mRNA and forms stable duplex in A-form. The linear dependence between the thermo-physical parameters such as T_m, GC content and binding free energy revealed the ability of the identified siRNAs to interact with mRNA in comparable to that of the experimentally reported siRNAs. Hence, this present study proposes few siRNAs as the possible gene silencing agents in RNAi therapy based on the in silico approach.     

A hybrid method of molecular dynamics and harmonic dynamics for docking of flexible ligand to flexible receptor

We have developed a new docking method to consider receptor flexibility, a hybrid method of molecular dynamics and harmonic dynamics. The global motions of the whole receptor were approximately introduced into those of the receptor in the docking simulation as harmonic dynamics. On the other hand, the local flexibility of the side chains was also considered by conventional molecular dynamics. We confirmed that this new method can reproduce the fluctuations of the whole receptor by making a comparison of the directions and amplitudes of the global fluctuations. Then this method was applied to the docking of HIV-1 protease and its ligand. As a result, we observed a docking process where the ligand enters into the binding pocket well, which implies that this method is effective enough to reproduce a molecular complex formation.     

An efficient parallelization scheme for molecular dynamics simulations with many-body, flexible, polarizable empirical potentials: application to water

An efficient parallelization scheme for classical molecular dynamics simulations with flexible, polarizable empirical potentials is presented. It is based on the standard Ewald summation technique to handle the long-range electrostatic and induction interactions. The algorithm for this parallelization scheme is designed for systems containing several thousands of polarizable sites in the simulation box. Its performance is evaluated during molecular dynamics simulations under periodic boundary conditions with unit cell sizes ranging from 128 to 512 molecules employing two flexible polarizable water models [DC(F) and TTM2.1-F] containing 1 and 3 polarizable sites, respectively. The time-to-solution for these two polarizable models is compared with the one for a flexible, pairwise-additive water model (TIP4F). The benchmarks were performed on both shared and distributed memory platforms. As a result of the efficient calculation of the induced dipole moments, a superlinear scaling as a function of the number of the processors is observed. To the best of our knowledge, this is the first reported results of parallel scaling and performance for simulations of liquid water with a polarizable potential under periodic boundary conditions.     

甲壳素铁卟啉制备及其催化空气氧化环己烷研究

首次采用甲壳素和四苯基铁卟啉制备高分子金属卟啉固载物 甲壳素四苯基铁卟啉 ,并用电镜 ,紫外和红外光谱技术对它进行表征 ,测定了铁卟啉在甲壳素上的表观吸附常数 ,研究了其催化性能 .研究结果表明 :四苯基铁卟啉能牢固地固载在甲壳素上 ,其表观吸附常数为 6 .80× 10 4L·mol-1.在无溶剂 ,无助催化剂和还原剂的体系中 ,它能高效催化空气氧化环己烷生成环己酮和环己醇 ,在 4 18K和 0 .8MPa的反应条件下 ,环己醇和环己酮选择性为 74 .5 % ,环己烷的摩尔转化率为 14 .79% ,催化剂转化数达到 3.80× 10 5.相对未固载的四苯基铁卟啉催化剂转化数 (按铁卟啉计 )提高了 2 1倍 .     

金催化剂催化环己烷液相选择氧化研究

采用溶胶-凝胶法制备了一系列担载纳米金催化剂,用于催化环己烷液相选择氧化反应.在反应体系中没有加入任何溶剂或助催化剂,考察了反应温度、时间、压力和不同焙烧温度对催化剂活性的影响.实验结果表明,催化剂在250℃焙烧和金含量为0.032%时,环己烷选择氧化可以达到10.8%的转化率和90.8%的目的产物(环己醇和环己酮)选择性,相应转化频率高达5.2×104.     

Molecular surface-volume and property matching to superpose flexible dissimilar molecules

Summary Steric complementarity is a prerequisite for ligand-receptor recognition; this implies that drugs with a common receptor binding site should possess sterically similar binding surfaces. This principle is used as the basis for an automatic and unbiased method that superposes molecules. One molecule is rotated and translated to maximize the overlap between the two molecular surface volumes. A fast grid-based method is used to determine the extent of this overlap, and this is optimized using simulated annealing. Matches with high steric similarity scores are then sorted on the basis of both hydrogen-bond and electrostatic similarity between the matched molecules. Flexible molecules are treated as a set of rigid representative conformers. The algorithm has correctly predicted superpositions between a number of pairs of molecules, according to crystallographic data from ligands that have been co-crystallized at common enzyme binding sites.     

气相色谱法分离正己烷和环己烷的实验设计与教学探索

The experiment of separating low toxic n-hexane and cyclohexane by traditional gas chromatography was improved with orthogonal experimental design. The effect of sample quantity, vaporization chamber temperature, detector temperature, column temperature, line velocity and separability of the split ratio were examined. Through the experiment, students could understand the use and maintenance of gas chromatography instruments. At the same time, they could understand separability and column efficiency of chromatography.     

乙酰葡萄糖氧代金属卟啉的合成及其对环己烷羟基化反应的催化作用

由吡咯和葡萄糖取代苯甲醛直接缩合制备了两种葡萄糖取代卟吩:四(邻位乙酰葡萄糖氧代苯基)卟吩和四(间位乙酰葡萄糖氧代苯基)卟吩,进一步金属化合成了4种葡萄糖金属卟啉:氯化四(邻位乙酰葡萄糖氧代苯基)卟吩合铁、氯化四(间位乙酰葡萄糖氧代苯基)卟吩合铁、氯化四(邻位四乙酰葡萄糖氧代苯基)卟吩合锰和氯化四(间位乙酰葡萄糖氧代苯基)卟吩合锰.它们的结构由紫外-可见光谱、核磁共振和元素分析证实.研究了这些葡萄糖取代金属卟啉对亚碘酰苯常温常压下氧化环己烷反应的催化作用.研究结果表明,4种糖基金属卟啉催化下的环己烷反应产率和反应速率都比一般金属卟啉高.反应动力学分析表明,在常温常压下,糖基金属卟啉催化下的环己烷氧化反应具有酶催化反应的动力学关系.     

Internal viscosity in the dynamics of polymer molecules

We consider the internal viscosity (IV) of polymer molecules in solution, and investigate how the IV might depend on solvent viscosity η₀. From the Kirkwood model of a polymer, we derive in a nonrigorous manner two equations containing an IV, one equation valid for low η₀ and the other for high η₀, and we show that in these respective cases the coefficient of the IV is independent of η₀ and linearly dependent on η₀.     

DiTe2: Calculating the diffusion tensor for flexible molecules

We report on an extended hydrodynamic modeling of the friction tensorial properties of flexible molecules including all types of natural, Z-Matrix like, internal coordinates. We implement the new methodology by extending and updating the software DiTe [Barone et al. J. Comput. Chem. 30, 2 (2009)]. DiTe (DIffusion TEnsor) implements a hydrodynamic modeling of the generalized translational, rotational, and configurational friction and diffusion tensors of flexible molecules in which flexibility is described in terms of dihedral angles. The new tool, DiTe2, has been renewed to include also stretching and bending types of internal mobility. Furthermore, DiTe2 is able to calculate the friction and diffusion tensors along collective (or reaction) coordinates defined as linear combinations of the internal natural ones. A number of tests are reported to show the new features of DiTe2. As leitmotiv for the tests, the calmodulin protein is taken into consideration, described both at all-atom and coarse-grained levels. © 2018 Wiley Periodicals, Inc.     

核糖核酸酶在DAB-环已烷反胶束溶液中的活性

表面活性剂在有机溶剂中形成的反胶束可以增溶大量的水分子，很多水溶性的物质又可溶解在反胶束的核心水团当中，这些都已是不争的事实［1］．酶在反胶束中的溶解对蛋白质的萃取分离，生物合成等方面有着十分广阔的应用前景，已引起了广泛的注意，文献逐年增加［2－4］．核糖核酸酶A（RNaseA）分子量较小，性质稳定，活性的测定简便易行，很适于作为反胶束－酶体系的研究对象，但大部分研究集中在阴离子表面活性剂AerosolT（AOT）的反胶束体系上，而对其它表面活性剂反胶束－酶体系的研究很少［5，6］．Papadimitriou等曾发现．糜蛋白酶…