不同力场对B-DNA到A-DNA构型转变的影响

采用分子动力学模拟方法比较了最新版CHARMM和AMBER(包括bsc1和OL15)力场对水溶液中B-DNA到A-DNA转化过程的影响,利用扩展自适应偏置力(eABF)方法计算了转化过程的自由能变化.研究结果表明,在不同力场下,水环境中的DNA最稳定结构存在差异,AMBER力场比CHARMM力场更符合实验结果.AMBER力场下DNA最稳定结构的小沟较窄,稳定于B构型;而CHARMM力场下DNA最稳定结构的小沟较宽,介于B构型与A构型之间.通过分析DNA周围离子及水的分布情况发现,CHARMM力场下DNA小沟周围的离子密度明显低于AMBER力场,不能很好地抵消2条磷酸骨架之间的排斥作用,这是CHARMM力场下小沟较宽且趋向A构型的主要原因.     

近边X射线吸收精细结构光谱法研究土壤腐殖质组分含碳官能团组成及磷酸根影响

应用同步辐射近边X射线吸收精细结构(NEXAFS)光谱技术研究了土壤腐殖质各组分(富里酸、胡敏酸及胡敏素等)的含碳官能团组成信息,并通过分析PO43-存在条件下胡敏酸、胡敏素的官能团组成变化特征,探讨了PO43-与土壤腐殖质之间的微观作用机制。结果表明,土壤腐殖质不同组分的官能团分布具有类似的光谱特征,但组成比例存在明显差异。随着腐殖质组分的酸不溶性增加,胡敏酸、胡敏素疏水性脂肪基官能团比例显著高于富里酸,芳构化程度也明显增加,而亲水性羧基官能团比例趋于降低;PO43-通过静电作用、取代反应可以选择性释放胡敏酸中部分小分子羧基官能团,从而改变胡敏酸官能团的组成特征。此研究结果对于应用NEXAFS研究有机碳官能团形态、结构及理解PO43-在土壤微界面上的反应机制具有重要意义。     

土壤腐殖质各组分红外光谱研究

土壤腐殖质是土壤中所特有的一类特殊的高分子化合物,具有重要的肥力和环境调节功能。其中胡敏素的提取和纯化很困难,从而限制了对其性质和结构的研究。为揭示胡敏素的结构性质,本研究按Pallo分组,将胡敏酸(HA)分为焦磷酸钠提取的胡敏酸(HAP)、氢氧化钠提取的胡敏酸(HAS);富里酸(FA)分为焦磷酸钠提取的富里酸(FAP)和氢氧化钠提取的富里酸(FAS);胡敏素(HM)分为铁结合胡敏素(HMi)、粘粒结合胡敏素(HMc)和不溶性胡敏素(HMr)三个组分,采用红外光谱法对黑土、草甸土以及黑土底土加入大量玉米秸秆培养后腐殖质各组分的结构特征进行研究。腐殖质各组分按Pallo法分组。结果表明:铁结合胡敏素(HMi)、粘粒结合胡敏素(HMc)与胡敏酸(HA)、富里酸(FA)具有相似的光谱特征,但存在明显差异。黑土、草甸土中HMi和HMc的脂族性强于HA和FA;HMi与HMc相比,HMi具有较高的脂族性。黑土中氢氧化钠提取的胡敏酸(HAS)的脂族性强于焦磷酸钠提取的胡敏酸(HAP);NaOH提取的富里酸(FAS)的脂族性强于Na4P2O7提取的富里酸(FAP)。草甸土中HAP的脂族结构较多,而HAS脂族结构相对较少。在培养土中,新形成的FA脂族性强于HA、HMi和HMc组分。新形成的HMc脂族性强于HMi和HMc的脂族性强于HAP,而弱于HAS。     

EK多肽折叠以及离子浓度和pH值依赖性的计算研究

我们分别运用了传统AMBER03力场以及极化力场研究了EK多肽在不同离子浓度和pH值条件下的折叠.其中极化力场源于我们近期发展的可调的氢键专一性电荷方案.这两种力场的差别仅仅在于原子电荷的不同.溶剂化效应用推广的波恩模型描述.结果表明,当使用AMBER03电荷时,尽管多肽倾向于形成螺旋结构,但是对离子浓度和pH值的依赖关系定性上是错误的.而当使用可调的氢键专一性电荷方案时,EK多肽在10ns内就达到了折叠态.在高离子浓度或者极端pH条件下,计算得到的螺旋结构的概率降低.对于原子电荷以及主链氢键相互作用的分析表明极化效应增加了螺旋结构的稳定性.该研究结果再一次证明了静电极化效应对提高传统力场的精度以及对蛋白质折叠的研究都是非常必要的.进一步的分析说明,间隔4个残基的盐桥作用虽然对稳定蛋白质结构起到了一定的效果,但并不是关键作用,这和实验是吻合的.     

室温离子液体的分子动力学模拟

室温离子液体作为一种新型的反应介质正在受到人们的关注,近十年来成为了化学领域的研究热点。随着人们对离子液体结构与性质研究的不断深入和计算方法的快速发展,分子模拟已是研究离子液体的结构和性质的有力工具。本文介绍了分子动力学(molecular dynamics,MD)的基本原理,分子力场的种类,以及离子液体分子动力学模拟一般采用的AMBER、OPLS和CHARMM三种力场的构建形式。综述了近年来纯组分离子液体、混合组分离子液体分子动力学模拟方法研究取得的成果和最新进展,并分析了主要存在的问题。展望了离子液体分子动力学模拟的研究方向和前景,同时还提出了包含极化作用和静电远程作用的离子液体分子动力学模拟研究的基本思路。     

超支化聚合反应的多尺度模拟

超支化聚合物具有与树枝状大分子相似的物理和化学性质,其具有合成简单、分子量分布宽等突出特点,超支化聚合物分子的结构形成取决于聚合反应过程,本文介绍了超支化聚合反应模拟研究的最新进展.首先介绍了八位置键涨落粗粒化格子模型在超支化聚合反应模拟中的应用,该方法考虑了聚合物分子空间位阻效应、分子内成环和反应点活性等影响因素,从而可以模拟不同类型的超支化聚合反应;为了定量描述单体和聚合物分子结构,研究者进一步发展了杂化多尺度超支化聚合反应模拟方法,该方法通过玻尔兹曼反演迭代方法获取单体和聚合物特异性粗粒化力场,然后通过粗粒化分子动力学方法结合反应性Monte Carlo方法对特异性超支化聚合反应进行定量模拟.多尺度聚合反应模拟不仅可以精确计算超支化聚合物分子量、多分散性指数和支化度等一般性聚合物参数,还可以获取分子成环率、超支化大分子构象等重要分子结构信息,在超支化聚合反应基础研究与预测方面具有重要应用价值.     

分子模拟技术在高分子科学实验中的应用

分子模拟技术是一项成熟的、有潜力的计算机实验技术,计算机具备高速稳定的图形处理能力,可以将实验结果以数据和图形的形式呈现出来,数据库技术可以方便的提取和存储各种分子模型和聚合物片段,通过可视化的三维图形的让学生更容易理解高分子科学的抽象概念,分子动力学的计算方法以牛顿力学为基础,在一定力场下建立周期性边界条件模型,通过几何构型优化和动力学运算,直观地了解到高分子的近程结构和聚集态结构,计算得出普通高分子实验无法得到微观相态结构,丰富了实验内容,开拓了高分子科学实验的新领域。     

锑胁迫下腐殖质对头花蓼体内锑形态及生化特性影响

锑(Sb)是一种无延展性的有色金属,具有潜在毒性和致癌性,对心血管、呼吸系统和肝脏等都会造成危害。并且,随着近几年锑资源的持续开发,土壤中的Sb污染被广泛关注。腐殖质具有复杂结构并包含有羧基、醇羟基等多种活性官能团,对重金属在土壤中的形态转化、迁移能力以及生物可利用性具有重要影响。头花蓼作为民间常用草药并且也是贵州省特色苗药,在土壤Sb背景值极高的独山锑矿区不仅能大量生长,并且在其体内Sb含量远高于其他未受污染的陆生植物时,仍然可以表现出良好的生长状态。为了探究腐殖质对独山矿区内Sb污染土壤中头花蓼植物有效性的影响。选取贵州省独山县东峰Sb区附近Sb污染土壤与头花蓼种子作为试验样品,通过三种不同腐殖质富里酸、胡敏素、胡敏酸对Sb污染土壤进行30d的培育实验后种植头花蓼。结果表明：(1)腐殖质添加后使得头花蓼叶绿素总量整体呈现上升的趋势,加强了头花蓼光合作用。(2)头花蓼的逆境生理现象表现为：在低添加量下,胡敏素实验组与胡敏酸实验组中丙二醛含量下降,SOD酶活性升高,CAT酶活性下降;说明胡敏素和的胡敏酸在低添加量下能够有效缓解头花蓼所受到的Sb毒害;而高添加量富里酸对头花蓼有一定损害。(3)低添加量的胡敏酸能够有效缓解头花蓼植株所受到的重金属Sb、As、Cd、Cu胁迫。(4)相比于胡敏素和胡敏酸,富里酸更容易促进头花蓼体内残渣态Sb向更活跃的赋存形态转化;胡敏酸对头花蓼中的Sb赋存形态表现出了低浓度活化而高浓度钝化的现象;胡敏素则能够有效降低头花蓼体内Sb活性。     

ABEEM/MM浮动电荷力场应用于血红素结构的研究

运用拟合的参数, 应用ABEEM/MM浮动电荷力场对血红素分子结构进行了模拟. 结果表明, 该力场与CHARMM力场相比, 能更好地模拟晶体结构. 计算的ruffing构象能与B3LYP/6-31G*计算结果的线性相关系数在0.98以上, 同时表明血红素分子中twist-angle对ruffing构象具有明显影响. ABEEM/MM力场计算的细胞色素c552中血红素分子的电荷分布与CHARMM固定电荷力场的比较, 更准确地反映了血红素分子的电荷分布以及极化现象.     

乙醇醛的分子动态结构

以量子化学计算作为起点, 为最简单的糖类分子——乙醇醛开发了两套分子力学力场参数: 基于肽类的力场和基于醛类的力场. 分子动力学模拟结果表明, 所开发的类醛力场参数能够较好地描述乙醇醛分子在水中的结构以及水分子在其周围的分布. 通过瞬时简正模式分析, 得到了3N-6个模式的瞬时振动频率和振动跃迁偶极矩等振动光谱参数的统计分布及其相关性. 结合量子化学计算和分子动力学模拟对生物分子体系的多元振动光谱参数进行预测和评估, 为从化学键水平出发模拟宽带飞秒二维红外相关光谱提供了一个新方法.     

Molecular Dynamisc Simulation of Polyelectrolites

We carried out simulations of a polymer chain using molecular dynamics algorythm. As a model we used a three-dimensional set monomers (electrically charged material points) connected with its nearest neighbours by harmonic potential. Additionally all pairs of segments interacts by the Lennard-Jones (LJ) and Coulomb forces. The aim of the simulation was to determine chain conformation and other basic properties like radius of gyration and moment of inertia for various polymer length and electric charge distribution.Presented model could be alternative tool for structure prediction to typically used ones based on AMBER 99 [1] or another advanced force field.     

Effects of all-atom force fields on amyloid oligomerization: replica exchange molecular dynamics simulations of the Aβ(16-22) dimer and trimer

The aim of this work is to investigate the effects of molecular mechanics force fields on amyloid peptide assembly. To this end, we performed extensive replica exchange molecular dynamics (REMD) simulations on the monomer, dimer and trimer of the seven-residue fragment of the Alzheimer's amyloid-β peptide, Aβ(16-22), using the AMBER99, GROMOS96 and OPLS force fields. We compared the force fields by analysing the resulting global and local structures as well as the free energy landscapes at 300 K. We show that AMBER99 strongly favors helical structures for the monomer and does not predict any β-sheet structure for the dimer and trimer. In contrast, the dimer and trimer modeled by GROMOS96 form antiparallel β-sheet structures, while OPLS predicts diverse structures. Overall, the free energy landscapes obtained by three force fields are very different, and we also note a weak structural dependence of our results on temperature. The implications of this computational study on amyloid oligomerization, fibril growth and inhibition are also discussed.     

Theoretical Study on the Effects of Spatial Structure of P Complexation Sites on the Soil Phosphorus Activation in Leonardite Humic Acid Complexes

Humic acid is an important active component in soil environment. The spatial structures of P complexation sites in humic acid complexes play an important role in soil phosphorus activation and fertilizer efficiency. To explore the effects of spatial structure, the three different coordination modes of iron-carboxyl in models were calculated by the ONIOM method available in the Gaussian09 package. The(U)B3LYP hybrid density functional was employed to optimize the configuration for the QM region, and the UFF force field was used to calculate for the MM region. The results show that the different spatial structures influence the soil phosphorus activation by affecting the electronic structure, Gibbs free energy and interaction energy of the models. And the effects are as follows: the unidentate structure model ~6P-Fe-MHA-UD, the bidentate chelating structure model ~6P-Fe-MHA-BD>the bidentate bridging structure model ~5P-Fe-MHA-BD-BG. It can be known that, the fertilizer efficiency can be improved through increasing the proportion of the unidentate structure and the bidentate chelating structure in production engineering. The research provides a theoretical basis for further optimization of the production of humic acid phosphate fertilizer.     

Partition coefficients of methylated DNA bases obtained from free energy calculations with molecular electron density derived atomic charges

Partition coefficients serve in various areas as pharmacology and environmental sciences to predict the hydrophobicity of different substances. Recently, they have also been used to address the accuracy of force fields for various organic compounds and specifically the methylated DNA bases. In this study, atomic charges were derived by different partitioning methods (Hirshfeld and Minimal Basis Iterative Stockholder) directly from the electron density obtained by electronic structure calculations in a vacuum, with an implicit solvation model or with explicit solvation taking the dynamics of the solute and the solvent into account. To test the ability of these charges to describe electrostatic interactions in force fields for condensed phases, the original atomic charges of the AMBER99 force field were replaced with the new atomic charges and combined with different solvent models to obtain the hydration and chloroform solvation free energies by molecular dynamics simulations. Chloroform–water partition coefficients derived from the obtained free energies were compared to experimental and previously reported values obtained with the GAFF or the AMBER‐99 force field. The results show that good agreement with experimental data is obtained when the polarization of the electron density by the solvent has been taken into account, and when the energy needed to polarize the electron density of the solute has been considered in the transfer free energy. These results were further confirmed by hydration free energies of polar and aromatic amino acid side chain analogs. Comparison of the two partitioning methods, Hirshfeld‐I and Minimal Basis Iterative Stockholder (MBIS), revealed some deficiencies in the Hirshfeld‐I method related to the unstable isolated anionic nitrogen pro‐atom used in the method. Hydration free energies and partitioning coefficients obtained with atomic charges from the MBIS partitioning method accounting for polarization by the implicit solvation model are in good agreement with the experimental values. © 2018 Wiley Periodicals, Inc.     

Impact factors and thermodynamic characteristics of aquatic humic acid loaded onto kaolin

The adsorption of humic acid (HA) on kaolin particles was studied at various conditions of initial solution pH, ionic strength and solid-to-liquid ratio. The resulting affinity of interactions between humic acid and kaolin was attributed to the surface coordination of HA in ambient suspensions of mineral particles and the strong electrostatic force at low pH. Addition of inorganic salt can also influence the adsorption behavior by affecting the HA molecular structure, the clay particle zeta potential and so on. Equilibrium data were well fitted by the Freundlich model and implied the occurrence of multilayer adsorption in the process. In addition, the enthalpy dependent of system temperature was 79.17 kJ/mol, which proved that the mechanism of HA adsorption onto kaolin was comprehensive, including electrostatic attraction, ligand complexation and hydrogen bonding.     

泥炭土连续碱抽提腐殖酸的分子结构特征

从Pahokee泥炭土中连续碱抽提分离出8个不同的腐殖酸级分，并对每一级分进行了元素分析、傅里叶变换红外光谱（FTIR）、固态^13C核磁共振（^13CNMR)、高效排阻色谱（HPSEC）等一系列定性、定量研究。结果表明：所分离出的8个腐殖酸级分存在明显的结构性质差异，随提取和蔼的增加，O／C原子比由0．52减少到0．36，H／C原子比由1．05增加到1．52，相应于结构中含氧基团的减少和脂族基的增加，表观分子量也由7．7K增加到22．1K。同时，^13C NMR显示长链脂肪碳结构由无定型向晶型转变。此工作表明在所研究的腐殖酸中可能存在分别具有芳香或脂肪特性的两类腐殖酸结构，每种类型都有不同的分子量分布、元素组成、基团结构和母质来源。在特定的环境因素下，不同类型的腐殖酸会共存于同一体系中，增加了腐殖物质的非均匀性和复杂性。     

土壤胡敏酸的^13C核磁共振研究

胡敏酸(HA)是土壤有机质的重要组分,其结构性质与土壤形成和肥力特性有密切关系,长期以来一直是土壤化学研究的难点和重点之一。NMR是研究HA结构的有效手段。自Bar-ton和Schnitzer(1963)首次用~1H NMR研究土壤有机质以来,国外已先后应用~1H、~(13)C NMR和CP-MAS-~(13)C NMR等对土壤及其它来源的HA进行了许多研究,并取得引人注目的进展。但在国内,这方面研究还刚刚开始。本文应用~(13)C NMR方法对东北几种主要耕作土壤以及泥炭和猪粪的HA进行了结构表征,为土壤腐殖酸化学的基础研究提供了资料。     

Peptide plane can flip in two opposite directions: implication in amyloid formation of transthyretin

Transthyretin (TTR) is one of the known 20 or so human proteins that form fibrils in vivo, which is a hallmark of amyloid diseases. Recently, molecular dynamics simulations using ENCAD force field have revealed that under low pH conditions, the peptide planes of several amyloidogenic proteins can flip in one direction to form an alpha-pleated structure which may be a common conformational transition in the fibril formation. We performed molecular dynamics simulations with AMBER force fields on a recently engineered double mutant TTR, which was shown experimentally to form amyloid fibrils even under close to physiological conditions. Our simulations have demonstrated that peptide-plane flipping can occur even under neutral pH and room temperature for this amyloidogenic TTR variant. Unlike previously reported peptide-plane flipping of TTR using ENCAD force field, we have found two-way flipping using AMBER force field. We propose a new mechanism of amyloid formation based on the two-way flipping, which gives a better explanation of various experimental and computational results. In principle, the residual dipolar and hydrogen-bond scalar coupling techniques can be applied to the wild-type TTR and the variant to study the peptide-plane flipping of amyloidogenic proteins.     

Lennard-Jones parameters for the combined QM/MM method using the B3LYP/6-31G*/AMBER potential

A combined DFT quantum mechanical and AMBER molecular mechanical potential (QM/MM) is presented for use in molecular modeling and molecular simulations of large biological systems. In our approach we evaluate Lennard-Jones parameters describing the interaction between the quantum mechanical (QM) part of a system, which is described at the B3LYP/6-31+G* level of theory, and the molecular mechanical (MM) part of the system, described by the AMBER force field. The Lennard-Jones parameters for this potential are obtained by calculating hydrogen bond energies and hydrogen bond geometries for a large set of bimolecular systems, in which one hydrogen bond monomer is described quantum mechanically and the other is treated molecular mechanically. We have investigated more than 100 different bimolecular systems, finding very good agreement between hydrogen bond energies and geometries obtained from the combined QM/MM calculations and results obtained at the QM level of theory, especially with respect to geometry. Therefore, based on the Lennard-Jones parameters obtained in our study, we anticipate that the B3LYP/6-31+G*/AMBER potential will be a precise tool to explore intermolecular interactions inside a protein environment.