From Molecular to Process Simulation: Novel Approaches to the Prediction of Phase Equilibria and PVT Behavior Based on Molecular/Quantum Mechanics and Molecular Dynamics Simulations

Abstract

Actually, in modern process simulators, more than 75% of the code implemented is dedicated to physical properties estimation, calculation and predictions. Data banks storing pure component parameters and binary interaction parameters for phase equilibrium calculations are extensively used and continuously implemented in actual process simulators. This gives an idea of the important role physical properties availability plays in process simulation.

In this paper we propose a new way for coupling molecular and process simulation. The basic machinery is to resort to molecular/quantum mechanics and molecular dynamics simulation techniques for generating the parameters of some equations of state that will subsequently be used for the prediction of phase equilibria and PVT behavior of small and polymeric molecules as well. This information, in turn, will be used as input in the process simulator, thus creating a final and well-defined bridge between molecular and process simulations in chemical engineering.     

Modelling Metal Complexes of Calixarene Esters and Phosphine Oxides Using Molecular Mechanics

This paper focuses on the molecular modelling of a number of calixarene ester and phosphine oxide metal ion complexes. Monte Carlo conformational searches, in conjunction with the Merck Molecular Force Field, were carried out using Spartan SGI Version 5.0.1. running on Silicon Graphics O2 workstations. In the case of the calix[4]arene tetraesters, the optimised models strongly suggest that the selectivity of these ligands is strongly related to the eight-fold nature of the coordination with the Na⁺ ion, while coordination with the Li⁺ ion, for example, is merely three-fold. This feature of eight-fold coordination is also observed in the models of the complexes formed by the calix[4]arene tetraphosphine oxides with calcium. However, whereas the eight-fold coordination is unique to the model of the TPOL:Ca²⁺ complex among the ions modelled, this mode of coordination occurs for TPOS with sodium and potassium, in addition to calcium. This concurs with the observation that calcium selectivity is obtained with ion selective electrodes based on TPOL but not TPOS. Though the cavity in the calix[5]arenes PPOL and PPOLx and the calix[6]arene HPOL, in their uncomplexed form, are much larger than that of the corresponding calix[4]arenes, the pattern of selectivity is the same – the ligands are selective for calcium. The models of the complexes of these larger calixarenes, such as PPOL:Ca²⁺, strongly suggest that the reason for this similarity is that four of the available phosphine oxide groups complex with the calcium ion, and the others are forced away from the cavity region for steric reasons. The resulting eight-fold coordination, is therefore, similar to that of the calix[4]arenes studied.Electronic Supplementary Material available.     

Molecular Parameterisation and the Theoretical Calculation of Electrode Potentials

The difference in reduction potentials between ortho and para-benzoquinones has been calculated. The employs gas phase ab initio and semi-empirical computations in combination with free energy perturbation theory applied to gas and solution phase Monte Carlo simulations. The effects on calculated results of altering solute electrostatic parameterisation in solution phase simulations is examined. Atom centred charges derived from the molecular electrostatic potentials, MEPs, from optimised ab initio wavefunctions and charges generated by consideration of hydrogen bonded complexes are considered. Parameterisation of hydroxyl torsions in hydroquinone molecules is treated in a physically realistic manner. The coupled torsional system of the ortho-hydrobenzoquinone molecule is described by a potential energy surface calculated using gas phase AM1 semi-empirical computations rather than the simple torsional energy functions frequently employed in such calculations. Calculated differences in electrode potentials show that the electrostatic interactions of quinone and hydroquinone molecules in aqueous solution are not well described by atom centred charges derived from ab initio calculated MEPs. Moreover, results in good agreement with the experimental reduction potential difference can be obtained by employing high level ab initio calculations and solution phase electrostatic parameters developed by consideration of hydrogen bonded complexes.     

Molecular Mechanics Studies of Montmorillonite Intercalated with Tetramethylammonium and Trimethylphenylammonium

The intercalation of organoammonium cations into smectite structure is the important step in the technology of non-linear optical materials. In this study we investigated the structure of montmorillonite (MMT), intercalated with two organoammonium cations : tetramethylammonium (TMA) and trimethylphenylammonium (TMPA) using molecular mechanics simulations. The studies were focused to following aspects: arrangement of organoammonium cations in the interlayer, their positions and orientation with respect to silicate layers and their anchoring to the layers. The calculated (basal) d-spacings for MMT with TMA 14.29 Å and 15.36 Å for MMT with TMPA are in good agreement with X-ray diffraction data.     

分子模拟方法及其在分子生物学中的应用

常用的分子模拟方法有 :量子力学法、分子力学方法、蒙特卡洛法和分子动力学法。四种方法各有优势 ,共同成为分子模拟的组成部分。综述了分子模拟法在分子生物学中的应用 ,最后介绍了分子模拟的发展方向 ,并预测了其未来的发展趋势。常用的分子模拟方法有 :量子力学法、分子力学方法、蒙特卡洛法和分子动力学法。四种方法各有优势 ,共同成为分子模拟的组成部分。综述了分子模拟法在分子生物学中的应用 ,最后介绍了分子模拟的发展方向 ,并预测了其未来的发展趋势。     

基于多参数成像AFM的细胞及分子力学特性探测研究进展

原子力显微镜(AFM)的发明为微纳尺度下高分辨率探测天然状态生物样本的物理特性提供了强大工具,是对传统生化特性检测方法的有力补充.近年来,多参数成像模式AFM的出现使得人们不仅可以获取生物样本表面形貌特征,还能同时获取生物样本多种力学特性图(如杨氏模量、黏附力、形变等),为研究生物结构、力学特性及其生理功能之间的关联提供了新的技术手段.多参数成像AFM的生物医学应用研究为细胞/分子生理活动及相关疾病内在机理带来了大量新的认识.本文结合作者在AFM细胞探测方面的研究工作,介绍了多参数成像AFM工作原理,总结了多参数成像AFM在细胞及分子力学特性探测方面的研究进展,并对其存在的问题进行了讨论和展望.     

人肝癌细胞的IGF-BP1分子特性及内源性蛋白酶对其降解的研究

用SDS-PAGE电泳、高效液相色谱（HPLC）、质谱等方法,研究了人肝癌细胞（HepG2）分泌的胰岛素样生长因子结合蛋白-1（35S-IGF-BP1）的分子结构、特性,及其被内源性蛋白酶降解的特点．35S-IGF-BP1经抗体免疫沉淀、生化分离,纯化为均一体．其分子是由多个亚基构成的蛋白质,分子量约为27kD;细胞UMR、HepG2、H35。BRL3A分泌的蛋白酶能将35S-IGF-BP1催化水解成较小分子（14kD）的多肽．     

Molecular Mechanics: The Cross-conjugated Carbonyl Group in Heterocyclic Compounds. 2. Parameterisation (MM2) of the Adjacent C-O and C-N Bonds

The definition, in a previous paper, of a new type of carbon atom (type 44) in the MM2 force field, i.e. when it is cross-conjugated, implies the reparameterisation of the bonds adjacent to the carbonyl bond. By means of a statistical study based on data issued from the Cambridge Structural Data System, we propose here new σ dipole moments and new stretching parameters for the C(44)-O(41) and C(44)-N(40) bonds included in heterocyclic compounds. These stretching parameters, which are π-bond-order dependent, are quite satisfactory (mean of unsigned deviations: 0.023Å) within limited π-bond-order ranges: 0.25 to 0.32 for the C-O bond, 0.37 to 0.53, for the C-N bond. As for the C(44)=O(7) bond the parameters are generally inappropriate for compounds in which both atoms connected to the type 44 carbon are heteroatoms. The maximum deviation from the experimental bond length, for both bond types can reach ±0.03Å. Here also, part of the dispersion of the results could be attributed to the variation of the effective dielectric constant D from one crystal to another.     

Studies on the Molecular Weights of Esterase and Peroxidase Isozymes of Maize

The molecular weights of esterase and peroxidase isozymes of maize seedlings were directly determined by improved polyacrylamide gradient gel electrophoresis. The different isozyme bands developed in polyacrylamide slab gel electrophoresis (uniform gel) were identified in polyacrylamide gradient gel electrophoresis by means of isozyme variants. The molecular weights of esterase isozymes E1, E2, E3F, E3S, a, b, c, named according to isozyme patterns in uniform gel, are <20000, 35200, 33000, 38500, 29900, 28500, 34000 doltons respectively. The molecular weights of peroxidase isozymes PX4F and PX4S are 131000 and 149000 doltons respectively. According to the band location in uniform gel and in gradient gel, some biochemical properties of the isozyme bands and relationships between the isozyme bands were analyzed. The possible errors in the determination of smaller molecular weight isozymes are discussed.     

Molecular dynamics (MD) simulations for the prediction of chiral discrimination of N-acetylphenylalanine enantiomers by cyclomaltoheptaose (beta-cyclodextrin, beta-CD) based on the MM-PBSA (molecular mechanics-Poisson-Boltzmann surface area) approach

Molecular dynamics (MD) simulations were performed for the prediction of chiral discrimination of N-acetylphenylalanine enantiomers by cyclomaltoheptaose (beta-cyclodextrin, beta-CD). Binding free energies and various conformational properties were obtained using by the MM-PBSA (molecular mechanics Poisson-Boltzmann/surface area) approach. The calculated relative difference (DeltaDeltabinding) of binding free energy was in fine agreement with the experimentally determined value. The difference of rotameric distributions of guest N-acetylphenylalanine enantiomers complexed with the host, beta-CD, was observed after the conformational analyses, suggesting that the conformational changes of guest captured within host cavity would be a decisive factor for enantiodifferentiation at a molecular level.     

蝶呤型钼辅因子生物合成、运输及组装——潜在的药物靶标

钼辅因子作为氧化还原反应中的重要分子,参与硫、氮、碳的氧化还原代谢.钼辅因子主要分为两类:以铁硫簇为基础的铁钼辅因子和以亚钼蝶呤为基础的钼辅因子.钼-二-亚钼蝶呤-鸟苷二核苷钼辅因子(Mo-bis-MGD)是蝶呤型钼辅因子的重要成员之一,是硝酸盐还原酶的重要辅因子.膜结合硝酸盐还原酶介导的硝酸盐还原为细菌提供了氮源和能...     

苯丙酮尿症分子遗传学研究进展

苯丙酮尿症是由于苯丙氨酸羟化酶基因突变引起的常染色体隐性遗传病。文章综述了苯丙酮尿症中的苯丙氨酸羟化酶基因的定位、结构、突变、调控以及突变基因的体外表达和苯丙氨酸羟化酶的三维结构特点等分子遗传学进展,阐述了苯丙氨酸羟化酶基因的突变对苯丙氨酸羟化酶的体外表达及其三维结构的影响, 以及部分基因型与表型相关的分子机制。 Abstract: Phenylketonuria(PKU) is one kinds of autusomal recessive disease caused by phenylalanine hydroxylase(PAH) gene mutation. This article reviews the recent molecular heredity progress on the phenylalanine hydroxylase gene’s orientation、structureand gene mutation and gene regulation. At same time, mutation gene in vitro expression and the character of 3D structure of PAH in PKU are involved. In this paper, also discussed the inflence of vitro expression and 3D protein structure by gene mutations and the molecular mechanism of the relationship between genotype and phenotype in PKU patient.     

促葡萄糖转运蛋白基因家族的分子进化研究

葡萄糖转运蛋白是一个在结构上相似功能上不同的多基因家族（ＧＬＵＴ１－ＧＬＵＴ５）。由于这一组蛋白和体内的葡萄糖利用有关,因此被认为是糖尿病胰岛素抵抗（抗性）的一个候选基因。本文比较了不同种生物这一基因家族的氨基酸和核苷酸顺序;推测了亲水性和疏水性分布;计算了蛋白质和核苷酸的进化距离,并在此基础上构建了分子进化树。研究表明：这一基因家族具有高度的同源性、极为相似的亲水性和疏水性分布以及结构的对称性。提示这一基因家族起源于一个共同的祖先并可能通过基因的重复而形成。这一进化机制可能有利于氨基酸结构的稳定及抵抗突变的作用。由于邻元法构建的进化树其分支长度存在差异,提示在这一基因家族的进化过程中,各分支上的进化速率并不相同。蛋白质进化距离和核苷酸进化距离所构建进化树的差异提示了在基因组中可能存在隐匿替换。两种方法构建的进化树都提示了ＧＬＵＴ１、３、４在结构和功能上要更为保守。     

无花果蛋白酶在胍溶液中的分子折叠与活力变化研究

本文研究无花果蛋白酶（ＥＣ．３．４．４．１２）在不同浓度盐酸胍溶液中分子构象与活力变化关系。酶的内源荧光光谱,圆二色光谱与酶活力的变化表明：荧光光谱呈现二个明显的变化区域,低浓度胍（低于２ｍｏｌ／Ｌ）中,荧光发射峰基本不变,但荧光强度随胍浓度上升,随胍浓度断续增大（高于２ｍｏｌ／Ｌ）,酶的最大发射波长明显红移。当胍浓度低于１ｍｏｌ／Ｌ时,不仅不会使酶失活,反而使酶激活,当胍浓度高于１ｍｏｌ／Ｌ以上时,酶逐渐失活,使酶完全失活的胍浓度为６ｍｏｌ／Ｌ酶的圆二色光谱也随着胍浓度的改变而发生复杂的变化。将荧光变化,ＣＤ谱变化及活力改变结合起来,表明活力的激活与构象的明显变化似是同步发生的,从另一角度进一步说明酶活性部位柔性是充分表现酶活力所必需。     

利用分子生物学技术研究大熊猫的进展

分子生物学手段为大熊猫研究注入了前所未有的活力,并将大熊猫的研究工作带入一个崭新的阶段。本文着重回顾了最近十几年来分子生物学技术在大熊猫研究中的应用与研究成果。尤其是PCR、RAPD、RFLP等技术及新的遗传标记(如微卫星、小卫星等)的出现,使得人们在大熊猫的遗传多样性、分子系统发育及生态学等领域的研究取得的进展。最后,对分子生物学技术在这一领域中的应用前景进行了展望。     

A Review of Molybdenum Adsorption in Soils/Bed Sediments: Speciation,Mechanism, and Model Applications

Mo is an essential trace element for both plants and animals in low concentrations (<5 ppm). However, provoked by uncontrolled industrial waste releases in freshwater or seawater, it is plausible that excessive availability of soluble Mo(VI) would be potentially toxic. In the environment, soluble Mo(VI) is mainly present in anionic forms of molybdate (MoO₄ ^2?) and/or tetrathiomolybdate (MoS₄ ^2?). The fate and transport of soluble Mo(VI) anions in surface and subsurface aquatic environments is typically controlled by adsorption in acidic soils and sediment. As such, the ability of soils/bed sediments to retain Mo(VI) is a key to determine its general mobility in the aquatic environment. This article reviews the sources and distribution of Mo speciation in solution and Mo(VI) anions adsorption mechanisms in soils and bed sediments, and evaluates the surface adsorption complexation models at the solid-water interface to estimate Mo(VI) anions adsorption in these chemical systems. Mo(VI) anions adsorption mechanisms included MoO₄ ^2? and MoS₄ ^2? adsorption by several prevailing adsorbent contents (including clay, Fe, Al oxides, iron sulfide, manganese oxides, and organic matter) of soils and bed sediments, and the influence of the competitive adsorption of other anions (e.g., sulfate, selenate, phosphate, arsenate, silicate, or tungstate). Models to estimate Mo(VI) anions adsorption include the triple layer model (TLM), the diffuse layer model (DLM), the constant capacitance surface complexation model (CCM), and charge distribution multisite complexation model (CD-MUSIC).     

Accumulation of Molybdenum Cofactor in the Seeds of Di-, Tetra-, and Hexaploid Wheat of the Genus Triticum L.

Accumulation of molybdenum cofactor (Moco) in wheat seeds depends on plant ploidy and appears to be a genetically predetermined trait. The level of Moco in the low productive diploid is 2.5–4.0 times greater than that in the evolutionary younger and more productive hexaploid. The deficit of water and high air temperature induced a sharp rise (14 to 64 times) in the Moco content in the seeds, irrespective of the level of ploidy. Apparently, this is a nonspecific adaptive response of wheat to the adverse conditions.     

Molecular mobilities and the lowered osmolality of the chromaffin granule aqueous phase

Carbon-13 spin-lattice relaxation times, T₁, have been measured in whole adrenal medullary tissue slices, in suspensions of isolated chromaffin granules, in the reconcentrated chromaffin granule lysate, and in various model solutions containing catecholamines, ATP, chromogranins and Ca²⁺. Reorientational correlation times have been calculated at 10°C using T₁ data and nuclear Overhauser enhancemments for protonated carbons on both catecholamines and nucleotides. Correlation times in all media are relatively short and characteristic of highly fluid aqueous phases. Adrenalin and ATP exhibit substantial differences in correlation times in all media, however, the ratio γ_R(ATP):γ_R(catecholamine) ranging from 2.4 in simple 3:1 adrenalin-ATP solutions to 4 in intact chromaffin granules. This difference, as well as the relatively high absolute reorientational mobilities of both components, confirms the importance of labile ionic interactions between ATP and catecholamines, but rules out the presence of high concentrations of base-stacked structures. Participation of the chromogranins in ternary complexes with catecholamines and ATP appears to be of minor importance. Ionic interactions to the protein are not reflected in either ¹³C T₁ values or chemical shifts of arginine or glutamate sidechain resonances, or in the ¹³C chemical shifts of ATP or catecholamines. Very labile protein-ATP binding appears to be reflected in the correlation time measurements, however, which show selective immobilization of ATP relative to catecholamine in the presence of soluble protein. Osmotic measurements indicate that solutions containing adrenaline, ATP and Ca²⁺ are highly nonideal, but probably not sufficiently so to account fully for the osmotic stabilization of the chromaffin granule aqueous phase. Even in the absence of specific intermolecular complexation, the chromogranins, through their polyelectrolyte properties, exert a significant influence on the intragranular osmolality. The osmotic lowering due to polyion-counterion interactions has been estimated semiquantitatively using a theory developed by Oosawa.     

Comparative Molecular Docking Studies with ABCC1 and Aquaporin 9 in the Arsenite Complex Efflux

Arsenic is the most toxic metalloid present in the natural environment in both organic and inorganic arsenic forms. Inorganic arsenic is often more hazardous than the organic form. Arsenite and arsenate compounds are the major inorganic forms which are toxic causing severe human health dysfunction including cancer. Excretion of arsenic from the system is found elusive. Therefore, it is of interest to screen channel proteins with the arsenic complex in the different combination of arsenic, GSH (glutathione) and arsenic, selenium using docking methods. The mode of arsenic removal. The complex structure revealed the mode of arsenic binding efficiency with the receptor aquaporine 9 and ABCC1 channel protein. This provides insights to understand the mechanism of arsenic efflux. These inferences find application in the design, identification and development of novel nutracetucal or any other formulation useful in the balance of arsenic efflux.     

载脂蛋白多基因家族分子进化的研究

与脂质运输有关的载脂蛋白基因构成一个复杂的多基因家族。为探讨这种演化时间长的基因家族的进化规律,本文首先建立了一种在非均衡进化速率条件下计算系统发生树中任意分支长度的简易方法,并可在此基础上算出无根分支系统树中分歧年代的期望值。进一步对本文科１０个种属共２６种载脂蛋白的系统演作作了实际分析,结果提示：①ＡｐｏＡ－Ｉ＇ＡｐｏＡ－ＩＶ,ＡｐｏＥ及ＡｐｏＡ－ＩＩ的共同祖先可能在奥陶纪水生脊椎动物中就已存