计算机分子模拟在分子印迹技术中的应用

传统的分子印迹技术对模板分子、功能单体、交联剂、致孔剂等的筛选往往依靠经验,常通过反复实验对合成条件进行优化,存在实验周期长、耗材量大等问题。计算机分子模拟技术的应用在实验过程中起到可预见性指导作用,可以实现精准识别位点的裁制、识别驱动力的设计,通过结合能等物化特征参数计算优化识别体系的稳定性,从而合理选择模板分子、功能单体、交联剂、致孔剂,优化聚合条件,以提高聚合物识别特异性和亲和力,缩短实验周期,更符合绿色化学的理念。本文简单介绍了计算机分子模拟技术,重点对其在分子印迹技术中的指导作用进行了综述,并对其在分子印迹技术中的应用进行了展望。     

锌卟啉对氨基酸甲酯手性分子识别的理论研究

用Tripos力场和分子力学方法研究了手笥锌卟啉的最低能量构象,并用分子动力学模拟了锌卟啉对氨基酸甲酯的识别过程,发现锌卟啉与D-氨基酸酯结合能力强于L-氨基酸,这与热力学实验结果一致.     

化学库及分子差异性设计研究进展

组合化学是近年来发展起来的一种快速合成和平行筛选群体化合物的新方法。它可以用来设计先导化合物，也可以对药物分子进行结构改造。本文主要综述了化学库的合成以及计算机辅助组合化学的研究进展。     

分子及团簇的分子动力学模拟——介绍一个计算化学实验

分子动力学方法在化学及相关学科研究中的重要地位日趋凸显,但在本科化学实验中鲜有涉及,现有计算化学实验多侧重量子化学方法对分子性质的计算。为普及分子动力学模拟这一有力工具,同时帮助学生理解分子的动态行为,本文以丙氨酸二肽模型分子为例设计了一个简单的分子动力学模拟实验。通过本实验学生能初步掌握分子动力学模拟的基本原理、流程和分析方法,同时加深对物理化学中势能面等抽象概念的理解。本实验即可作为单独设课的计算化学实验的内容,亦可在物理化学实验中作为拓展实验开设。     

分子模拟法研究高性能树脂——聚苯撑苯并二噻唑分子链的构象与堆砌

分子模拟法研究高性能树脂──聚苯撑苯并二噻唑分子链的构象与堆砌刘跃，杨小震（中国科学院化学研究所高分子物理开放实验室，北京１０００８０）“分子模拟”是在原子水平上描述分体系的结构与行为的计算机模拟，是一个很新的领域。它的方法有：量子力学法、分子力学法...     

发光性受体的分子设计与分子识别

介绍了发光受体的几种典型分子识别模型。从分子识别与超分子化学的角度综述了它们在分子离子识别中的应用。对近几年发展较快的分子印迹技术及其应用进行了综述。引用文献71篇。     

应用分子图形学、分子力学、量子化学及静电势研究农药分子结构与性能的关系(Ⅲ)——一种获得有机分子优势构象的简单方法

通常可采用分子力学计算来得到有机分子的优势构象,但平常使用分子力学程序,由优化分子的构象得到的优化能,往往并不是分子的最低能量,而与分子的最初输入构象有关,是分子的初始输入构象附近的极小值,这给实际应用带来了困难.目前较为常规的求分子最优几何构象的方法是统计方法(Monte Carlo方法),通过模拟退火(The Simulated Annealing)来处理.开始“温度”较高的分子位于能量较高的位置上,这时分子的构象处于少数几个极小区     

药物分子设计和核酸的分子识别分析

分子识别分析理论应用于药物分子设计是新药开发的要求，也是分析化学一个极具潜力的发展方向，分子识别分析不仅为药物分子设计提供了生物大分子的组成，结构基基本信息，还为了解药物分子与生物大分子相互作用位点及作用方式提供了模型，本文评述了与药物分子设计中有关的核酸物质的分子识别分析，它们是设计好的抗癌药物的基础。     

化学结构通式的计算机表达与识别

引言结构通式(Generic Structure)是化学文献中用以表达具有某些共同性质及结构特征的一类有机化合物的最常见的化学符号,主要用于表达化学反应的规律,因此,受到国际化学文献出版与研究机构的广泛重视,结构通式的计算机表达与识别是化学专利文献的计算机检索系统,计算机辅助有机合成设计系统的关     

识别手性六螺烯分子的计算机模拟

手性拆分分子与手性分子间的短程相互作用会形成非对映异构体的接触对,从而导致的立体选择作用很难传统实验方法进行研究^[1]。蛋白质－核酸识别机理和研究表明,计算机模拟可以很好地研究这个问题^[2]。用高分子分离性分子的计算机模拟尚未见报道。     

Molecular Dynamics Simulations of Cellulose Oligomers: Conformational Analysis

Summary: The results of classical molecular simulations of cellulose oligomers are presented here. The conformations of the chains in the high temperature melt, room temperature quenched melt and gas phase are compared with respect to various geometrical parameters including square end‐to‐end distances, glycosidic link torsion correlations, ring puckering and hydrogen bonding. The cellulose oligomer melts were relaxed at 800 K with molecular dynamics, and then cooled down in three different ways to obtain dense amorphous systems at 500 K and at room temperature. The sample resulting from the quench (step) shows too much similarity with the melt at 800 K. The two other cooling schemes (ramp, 2ramps) give very similar results for all quantities investigated. The relevance of previous single molecule calculations with respect to the dense amorphous systems is called into question. Comparisons between the chains in the dense systems and those in the gas phase reveal that, even for these relatively short stiff chains, differences exist in the preferred conformations. At high temperatures, where both systems are in equilibrium, the distribution of square end‐to‐end distances are both fairly smooth, but the gas phase clearly prefers more compact conformations. At 300 K, the differences are exacerbated as the equilibrium distribution for the gas phase shows a high proportion of folded conformers, whereas the nonequilibrium quenched systems necessarily retain the extended envelope of the higher temperature. Differences are also evident in the puckering, the rotation of the hydroxymethyl groups and the pattern of hydrogen bonds.

The probability density distribution for the square end‐to‐end distance for octaose in the gas phase (light line) and in the dense phase (dark line) at 300 K.     

A Central Partition of Molecular Conformational Space. III. Combinatorial Determination of the Volume Spanned by a Molecular System

In the first work of this series (Gabarro-Arpa, Comp. Biol. Chem. 27 (2003) 153–159) it was shown that the conformational space of a molecule could be described to a fair degree of accuracy by means of a central hyperplane arrangement. The hyperplanes divide the space into a hierarchical set of cells that can be encoded by the face lattice poset of the arrangement. The model however, lacked explicit rotational symmetry, which made impossible to distinguish rotated structures in conformational space. This problem was solved in a second work (Gabarro-Arpa, Proc. 26th Ann. Int. Conf. of the IEEE EMBS (San Franciso, 2004) 3007–3010) by sorting the elementary 3-dimensional components of the molecular system into a set of morphological classes that can be properly oriented in a standard 3-D reference frame. This also made possible to find a solution to the problem that is being addressed in the present work: for a molecular system immersed in a heat bath we want to enumerate the subset of cells in conformational space that are visited by the molecule in its thermal wandering. If each visited cell is a vertex on a graph with edges to the adjacent cells, here it is explained how such graph can be built.     

谷胱甘肽分子伞的构象分析及VolSurf表征

使用分子动力学模拟迟火和半经验AMl方法对谷胱甘肽分子伞进行了构象分析 ，结果表明，真空下屏蔽构象和暴露构象的最低能量值相差很小(26.00kJ/mol)。 考虑溶剂效应后，屏蔽构象的能量值最高，暴露构象的能量值最低。屏蔽构象的能 量最低值高于暴露构象的能量最低值89.24kJ/mol，从理论上解释了谷胱甘肽分子 伞在水溶液中呈现暴露构象的原因。利用VolSurf参数分析了分子伞以屏蔽构象穿 透磷脂双分子层的影响因素，结果表明屏蔽构象较小的两亲矩及较大的分子褶皱程 度是其能够穿透细胞膜的主要影响因素，与构象的绝对疏水区域无关。     

Conformational analysis of 5,6-dihydropyrimidine and its derivatives

The equilibrium geometry and inversion barriers of 5,6-dihydropyrimidine, 6,7-dihydroazolopyrimidines with node nitrogen atoms and their alkyl (Me, Et, Prⁱ, Bu^t) and phenyl derivatives were calculated using a molecular mechanics approach. Annelation with azole cycles and the introduction of substituents have a slight effect on the equilibrium conformation of the dihydrocycle (distorted sofa). Alkyl substutuents at saturated carbons have an essentially equatorial orientation in 5,6-dihydropyridimine derivatives and are axial in the annelated analogs. On the other hand, the equatorial conformers are more stable in phenyl derivatives of dihydroazolopyrimidines. Factors determining the relative stability of conformers were analyzed.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 487–491, March, 1995.     

Conformational searching of transition metal compounds

To date, no conformational search of inorganic complexes has been reported that searches for all the conformations and configurations available to the complex. This is due to the various coordination geometries that transition metal ions can adopt and the difficulties in conducting conformational searches with systems that have connected ring systems, such as the ones formed when a metal ion binds a multidentate ligand. Using three test complexes {[Co(dien)₂]³⁺, [Co(dien)(dpt)]³⁺, and [Co(hexamethylcyclam)(Cl)} the ability of the random kick (Cartesian stochastic Monte Carlo search) method and the Monte Carlo dihedral and positional method to find all conformations and geometric isomers was tested (dien, diethylenetriamine; dpt, di(3-aminopropyl)amine; hexamethylcyclam: tet-a, meso-5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane; tet-b, racemic-5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane). Both methods are significant improvements on the current method by which all possible isomers are entered graphically and minimized individually. The major difficulty that was encountered was how to differentiate between the large number of similar conformations found. ©1999 John Wiley & Sons, Inc. J Comput Chem 20: 1549–1558, 1999     

Conformational analysis of sesquiterpene lactones of germacrane type

The structure of 1(10)Z,4Z-germacranolides was studied by the method of molecular mechanics. Possible conformers, the probability of their existence, and barriers to conformational transitions were determined. For Part 1, see Ref. 1. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 268–271, February, 1997.     

Conformational Dynamics of apo‐GlnBP Revealed by Experimental and Computational Analysis

The glutamine binding protein (GlnBP) binds l ‐glutamine and cooperates with its cognate transporters during glutamine uptake. Crystal structure analysis has revealed an open and a closed conformation for apo‐ and holo‐GlnBP, respectively. However, the detailed conformational dynamics have remained unclear. Herein, we combined NMR spectroscopy, MD simulations, and single‐molecule FRET techniques to decipher the conformational dynamics of apo‐GlnBP. The NMR residual dipolar couplings of apo‐GlnBP were in good agreement with a MD‐derived structure ensemble consisting of four metastable states. The open and closed conformations are the two major states. This four‐state model was further validated by smFRET experiments and suggests the conformational selection mechanism in ligand recognition of GlnBP.     

亮氨酸脑啡肽构象的分子动力学方法研究

采用淬火和模拟退火两种分子动力学的方法对亮氨酸脑啡肽进行了构象搜索，发现了多个Gly－Pheβ－Ⅱ’转角的低能构象．计算结果表明，高温淬火和模拟退火两者结合起来可以有效地寻找低能构象．     

Analysis of the Conformational Composition of 2-Alkyl-4-phenyl-1,3,2-oxazaborinanes

The empirical MM2 and semiempirical AM1 methods were used to calculate the energy of model 2-methyl-4-phenyl-1,3,2-oxazaborinane with full optimization of the molecular geometry. Comparison of the experimental coupling constants for the 2-isobutyl analog and calculated coupling constants as well as the data for the relative energy of the individual conformers indicated that these compounds form a multicomponent equilibrium system containing sofa and a family of half-chair forms.