螺旋手性SWCNT的尺寸对赖氨酸分子手性转变反应的限域影响

采用量子力学与分子力学组合的ONIOM方法,研究了两种构象的赖氨酸分子限域在螺旋手性单壁碳纳米管内的手性转变机理.结构分析表明:纳米管管径越小,限域在其中的赖氨酸分子骨架形变越明显,手性碳上的氢原子与氨基上氮的氮原子距离越小.势能面计算表明,两种构象的赖氨酸分子限域在SWCNT(6,4)时,旋光异构反应决速步的吉布斯自由能垒分别是194.72和170.08kJ·mol~(-1),分别由质子从手性碳向氨基氮和质子从手性碳向氨基氮与氨基上的质子向羰基氧双质子协同迁移的过渡态产生的.与裸反应的此通道决速步能垒252.6kJ·mol~(-1)相比较有显著降低.两种构象的赖氨酸分子限域在SWCNT(6,4)内旋光异构反应的表观能垒分别是160.00和178.59kJ·mol~(-1).他们限域在SWCNT(7,4)内时,旋光异构反应决速步的能垒分别是238.28和217.18kJ·mol~(-1);限域在SWCNT(8,4)内时,旋光异构反应决速步的能垒分别是253.00和250.11kJ·mol~(-1).结果表明:螺旋手性单壁碳纳米管的孔径越小,对赖氨酸分子手性转变反应的限域催化作用越好;限域在SWCNT(6,4)内的赖氨酸分子构象1更容易旋光异构.     

Kinetic redistribution of native and misfolded RNAs by a DEAD-box chaperone

DExD/H-box proteins are ubiquitously involved in RNA-mediated processes and use ATP to accelerate conformational changes in RNA. However, their mechanisms of action, and what determines which RNA species are targeted, are not well understood. Here we show that the DExD/H-box protein CYT-19, a general RNA chaperone, mediates ATP-dependent unfolding of both the native conformation and a long-lived misfolded conformation of a group I catalytic RNA with efficiencies that depend on the stabilities of the RNA species but not on specific structural features. CYT-19 then allows the RNA to refold, changing the distribution from equilibrium to kinetic control. Because misfolding is favoured kinetically, conditions that allow unfolding of the native RNA yield large increases in the population of misfolded species. Our results suggest that DExD/H-box proteins act with sufficient breadth and efficiency to allow structured RNAs to populate a wider range of conformations than would be present at equilibrium. Thus, RNAs may face selective pressure to stabilize their active conformations relative to inactive ones to avoid significant redistribution by DExD/H-box proteins. Conversely, RNAs whose functions depend on forming multiple conformations may rely on DExD/H-box proteins to increase the populations of less stable conformations, thereby increasing their overall efficiencies.     

Effects of metal ions on recombinant calcineurin A subunit

Effects of metal ions on activities and solution conformations of calcineurin A subunit have been examined. The ability of several metal ions to activate calcineurin A has been tested with Ni²⁺> Mn²⁺> Mg²⁺/Ca²⁺. The corresponding CD spectra and intrinsic fluorescent emission spectra show that calcineurin A exists in different metal ion-dependent conformation states. Effects of the different concentritions of Ni²⁺ on activities and solution conformations of calcineurin A have been tested too. Results indicate that effects of these metal ions to activate calcineurin are due to their conformational changes.     

分子力学在构象分析中的应用

主要采用MM2对一元取代和二元取代环已烷的构象进行了定量分析.在优化构象下,计算得到的结果与传统观念不相符;因此提出了前优化构象模型法,在前优化构象下的计算结果与传统观念完全一致.所以,可把前优化构象法应用于有机分子的构象分析中.     

Effect of protein packing structure on side-chain methyl rotor conformations

Protein molecules undergo a series of conformational fluctuations ranging in degree from atomic vibrations to transient denaturation, even in physiological conditions. The rotational motions of amino acid side chains form an important subset of the types of fluctuation a protein can undergo. NMR and molecular dynamics have shown that methyl groups in proteins are not held in fixed positions, but spin rapidly around their rotor axes. The question then arises as to whether methyl groups in proteins predominantly adopt the 'staggered' conformation, favoured by the intrinsic barrier to rotation of these groups, or whether cooperative packing effects in the folded protein perturb the average configurations to higher torsional energy. We report here an investigation of the rotational conformations of the methyl groups of aliphatic side chains in the protein crambin by neutron diffraction. We find that in the time-averaged structure of this protein, the majority of methyl rotors adopt the staggered conformation. This is consistent with rotation being a quantized event consisting of rapid reorientations of approximately 120 degrees steps to positions of highest stability. The fact that the local environment does not dictate the low energy state of methyl groups suggests that within the seemingly close-packed interior structure of a protein, mutual packing accommodation occurs as a consequence of the inherent flexibility and small packing defects in protein structures.     

Collapse of stiff conjugated polymers with chemical defects into ordered, cylindrical conformations

The optical, electronic and mechanical properties of synthetic and biological materials consisting of polymer chains depend sensitively on the conformation adopted by these chains. The range of conformations available to such systems has accordingly been of intense fundamental as well as practical interest, and distinct conformational classes have been predicted, depending on the stiffness of the polymer chains and the strength of attractive interactions between segments within a chain. For example, flexible polymers should adopt highly disordered conformations resembling either a random coil or, in the presence of strong intrachain attractions, a so-called 'molten globule'. Stiff polymers with strong intrachain interactions, in contrast, are expected to collapse into conformations with long-range order, in the shape of toroids or rod-like structures. Here we use computer simulations to show that the anisotropy distribution obtained from polarization spectroscopy measurements on individual poly[2-methoxy-5-(2'-ethylhexyl)oxy-1,4-phenylenevinylene] polymer molecules is consistent with this prototypical stiff conjugated polymer adopting a highly ordered, collapsed conformation that cannot be correlated with ideal toroid or rod structures. We find that the presence of so-called 'tetrahedral chemical defects', where conjugated carbon-carbon links are replaced by tetrahedral links, divides the polymer chain into structurally identifiable quasi-straight segments that allow the molecule to adopt cylindrical conformations. Indeed, highly ordered, cylindrical conformations may be a critical factor in dictating the extraordinary photophysical properties of conjugated polymers, including highly efficient intramolecular energy transfer and significant local optical anisotropy in thin films.     

9-硅蒽和9-锗蒽与烯烃杂Diels-Alder反应的理论研究

采用密度泛函理论方法在B3LYP/6-311G**水平研究了9-硅蒽和9-锗蒽与烯烃的杂Diels-Alder反应的微观机理、势能剖面,考察取代基对反应势能剖面的影响.计算结果表明,所研究反应均以协同非同步的方式进行,且Si(Ge)—C键总是先于C—C键形成.乙烯分子中C原子上的苯基取代基在热力学上对反应不利,但在动力学上的影响取决于产物中苯基与Si(Ge)原子之间的相对位置.9-硅(锗)蒽分子中Si(Ge)原子上的2,4,6-三甲基苯基取代基在热力学和动力学上均对反应不利.     

多环芳烃中苯的形成机理研究

为了研究多环芳烃中苯的形成过程,设计了3条可能的反应路径,采用Gaussian09中密度泛函的理论和UB3LYP/6-31++G(d,p)基组进行计算,以此为基础对苯的形成过程进行研究.对反应物,产物的几何构型进行优化,通过TS方法寻找过渡态,并用IRC路径分析验证了过渡态的可靠性.计算了不同温度下的反应的热力学参数,进行了热力学和动力学分析,结果表明:在不同温度下,路径1,2,3的ΔH均小于零,是放热反应,随着反应温度增加,焓变减少,反应放热增多,且路径1,2的ΔG均小于零,反应可自发进行,随着温度增加,反应物转化率变大,而路径3的ΔG大于零,反应基本不会进行.比较3个反应路径的活化能,所需活化能的大小顺序为1<3<2,因此路径1是最可能的反应路径.     

螺旋手性SWBNNT尺寸对Lys分子手性转变反应限域的影响

用量子力学与分子力学组合的ONIOM方法, 研究两种构象的赖氨酸(Lys)分子限域在螺旋手性单壁氮化硼纳米管(SWBNNT)内的手性转变机理. 结果表明： 限域 在小管径螺旋手性SWBNNT的Lys分子骨架形变明显; 当两种构象的Lys分子限域在SWBNNT(6,4)时, 旋光异构反应的表观能垒分别为17590,23044 kJ/mol, 旋光异构反应决速步骤的内禀能垒分别为21140,23044 kJ/mol, 来源于质子从手性C向氨基N迁移的过渡态, 比裸反应的决速步骤能垒(252.60 kJ/mol) 低. 即螺旋手性SWBNNT的管径越小, 限域催化作用越明显, 限域在SWCNT(6,4)内具有氨基与羧基间单氢键的Lys分子先旋光异构.     

CH_xO(x=1,2)与NH_y(y=0,1,2)自由基反应机理的理论计算

采用MP2方法,在6-311G**和6-311++G**基组水平上优化CH2O、CHO分别与N、NH、NH2发生吸氢反应时的过渡态结构,通过振动分析,对过渡态结构进行确认;在此基础上,应用IRC理论分析了最小能量途径(MEP)上相互作用分子间化学键的变化;采用QCISD方法在6-311++G**基组水平下对各反应驻点进行单点能量校正,计算了反应活化位垒.研究表明所有反应均以协同方式进行,从反应物CH2O与N、NH、NH2到最终产物CO、NH3,反应均放热,产物渐趋稳定;6个反应中,链式反应(1)、(5)是最容易的反应途径.通过反应途径的量子拓扑分析,发现CH2O与N、NH、NH2反应化学键的断开与形成基本上都处于过渡态(S=0)附近,CHO与N、NH、NH2反应时,键的形成和断开在过渡态之后.     

Hyperconjugation not steric repulsion leads to the staggered structure of ethane

Many molecules can rotate internally around one or more of their bonds so that during a full 360 degrees rotation, they will change between unstable and relatively stable conformations. Ethane is the textbook example of a molecule exhibiting such behaviour: as one of its two methyl (CH3) groups rotates once around the central carbon-carbon bond, the molecule will alternate three times between an unstable eclipsed conformation and the preferred staggered conformation. This structural preference is usually attributed to steric effects; that is, while ethane rotates towards an eclipsed structure, the electrons in C-H bonds on the different C atoms are drawing closer to each other and therefore experience increased repulsion, introducing a rotation barrier that destabilizes the eclipsed structure. Stabilization of the staggered structure through rotation-induced weakening of the central C-C bond and hyperconjugation has been considered to be involved, but evaluation of the contributions of these effects to ethane's internal rotation barrier and conformational preference remains difficult. Here we report a series of ethane structure optimizations, where successive removal of different interactions indicates that ethane's staggered conformation is the result of preferential stabilization through hyperconjugation. Removal of hyperconjugation interactions yields the eclipsed structure as the preferred conformation, whereas repulsive forces, either present or absent, have no influence on the preference for a staggered conformation.     

Phenol stabilizes more helix in a new symmetrical zinc insulin hexamer

SINCE insulin was first shown by Scott to crystallize in the presence of zinc ions in 1934, a variety of Zn-containing insulin crystals have been grown. The structures of insulin in the related rhombohedral crystals of 2Zn-insulin and 4Zn-insulin have been solved and reveal that the molecule is a hexamer, organized as three dimers, each containing a 2-fold symmetry axis and held together by Zn ions. In 2Zn-insulin the hexamer is nearly symmetrical with the two axial Zn ions and the two molecules of the dimer related closely by a local 2-fold axis. But in 4Zn-insulin the two molecules in the dimer differ remarkably, creating an asymmetric 4Zn-hexamer in which one trimer is essentially equivalent to that in 2Zn-insulin and the other is different by virtue of an additional stretch of N-terminal helix between residues B1 and B8 (refs 6, 7). We report here the structure of a new symmetrical hexamer, in which all six molecules have the B1-B8 helix seen in 4Zn-insulin. Phenol molecules, found bonding specifically to each molecule, evidently stabilize this new helical conformation.     

Circular dichroism spectroscopic studies on structures formed by telomeric DNA sequences in vitro

Telomere plays an important role in cellular processes, such as cell aging, death and carcinogenisis. Having special sequences, it can form quadruplex structure in vitro. Circular dichroism (CD) spectroscopic studies show that TTAGGG, (TTAGGG)2 and (TTAGGG)4 can all form quadruplex in vitro and exist mainly as parallel quadruplex without metal ions. Both K+ and Na+ can stabilize the tetrameric structure and facilitate the forming of anti-parallel conformation. Furthermore, the conformations of quadruplex can also be affected by sequence length, the nature and concentration of metal ions.     

The dead-end elimination theorem and its use in protein side-chain positioning

The prediction of a protein's tertiary structure is still a considerable problem because the huge amount of possible conformational space1 makes it computationally difficult. With regard to side-chain modelling, a solution has been attempted by the grouping of side-chain conformations into representative sets of rotamers2??. Nonetheless, an exhaustive combinatorial search is still limited to carefully indentified packing units?? containing a limited number of residues. For larger systems other strategies had to be developed, such as the Monte Carlo Procedure?? and the genetic algorithm and clustering approach?. Here we present a theorem, referred to as the 'dead-end elimination' theorem, which imposes a suitable condition to identify rotamers that cannot be members of the global minimum energy conformation. Application of this theorem effectively controls the computational explosion of the rotamer combinatorial problem, thereby allowing the determination of the global minimum energy conformation of a large collection of side chains.     

生物柴油多组分替代混合物化学反应路径分析

采用MD、MD9D和正庚烷三组分作为生物柴油混合替代物,替代物机理包含3 299种组分、10 806个基元反应。应用CHEMKIN-PRO反应速率分析法对燃烧氧化过程中燃料分子高低温主要反应路径和重要中间组分衍化过程进行了详细探究。结果表明:MD和MD9D在低温阶段主要通过脱氢加氧、异构化反应以及酮类物质的分解反应进行消耗,高温阶段主要是低温反应中间产物C—O、C—C键β分解反应、部分高温脱氢以及异构化反应最终生成C_2H_4等小分子产物。另外,MD和MD9D中不同碳原子位置C—H键能不同,邻近羧基以及C≡C双键碳原子处C—H键较弱,易发生脱氢反应生成烷酯基。在过氧酯基异构化生成过氧羧酯基过程中,不同环数过渡环张力大小以及反应势垒不同,异构化难易程度不同,而六元过渡环的张力较小,反应势垒较低,最易发生异构化反应,异构化反应产物更多。     

5-取代丙二酸亚异丙酯构象的量子化学研究

5-取代丙二酸亚异丙酯衍生物构象目前还有争议,我们用半经验分子轨道的MNDO方法对其三种有代表意义的分子进行了量子化学计算,得出一些有意义的结果。确定5-(甲基)丙二酸亚异丙酯的稳定构象为椅式;5-(甲酰甲基)丙二酸亚异丙酯的稳定构象为船式;5-(肟基)丙二酸亚异丙酯的稳定构象为信封式,并对不同构象的成因作了探讨。     

关于碳正离子的稳定性和反应性

碳正离子的稳定性与其在反应中的活性表现是基本一致的，越稳定的碳正离子，其反应活性越高，但是，含有π体系的碳正离子在不同的反应中，稳定性与其反应的关系不同，本文通过碳正离子的ＰＫＲ＾＋值、气态氢化合合能数据及有关反应的速率常数值来说明烷基碳正离子、苄基型及烯丙型碳正熟子、桥头炭正离子在反应中的稳定性及其与反应活性的关系。     

苏氨酸分子的构象转变及水分子与羟基自由基的催化机理

采用密度泛函理论的B3LYP方法和微扰论的MP2方法, 研究苏氨酸分子构象转变机制以及水分子与羟基自由基对氢迁移反应的催化作用. 结果表明： S-苏氨酸向R 别苏氨酸的构象转变反应有4个通道, R-别苏氨酸向R-苏氨酸与S-苏氨酸向S-别苏氨酸的构象转变反应各有1个通道; S-苏氨酸向R-别苏氨酸构象转变反应的最高能垒为250.2 kJ/mol; R-别苏氨酸向R-苏氨酸构象转变反应的最高能垒为335.0 kJ/mol; S-苏氨酸向S-别苏氨酸构象转变反应的最高能垒为359.6 kJ/mol; 2个水分子构成的链及水分子/羟基自由基构成的链对质子迁移反应有较好的催化作用, 使S-苏氨酸向R-别苏氨酸构象转变反应的高能垒分别降为128.3 kJ/mol和108.6 kJ/mol.     

丁酸甲酯高温分解的过渡态理论研究(英文)

选取了丁酸甲酯高温分解的十三个反应路径中较为重要的两个反应:CH3OCO=CH3+CO2(R1)和CH3OCO=CH3O+CO(R2).使用密度泛函理论方法在B3LYP/TZVP基组水平上寻找了反应的过渡态,并且得到了两个反应的势能曲线.R1的势垒高度远远低于R2,同时R1的产物CH3和CO2拥有较低的能量,处于相对稳定的状态.因此,反应CH3OCO=CH3+CO2更容易发生.结论为丁酸甲酯的动力学模型研究提供了一定的理论依据.     

Probing the free-energy surface for protein folding with single-molecule fluorescence spectroscopy

Protein folding is inherently a heterogeneous process because of the very large number of microscopic pathways that connect the myriad unfolded conformations to the unique conformation of the native structure. In a first step towards the long-range goal of describing the distribution of pathways experimentally, F?rster resonance energy transfer (FRET) has been measured on single, freely diffusing molecules. Here we use this method to determine properties of the free-energy surface for folding that have not been obtained from ensemble experiments. We show that single-molecule FRET measurements of a small cold-shock protein expose equilibrium collapse of the unfolded polypeptide and allow us to calculate limits on the polypeptide reconfiguration time. From these results, limits on the height of the free-energy barrier to folding are obtained that are consistent with a simple statistical mechanical model, but not with the barriers derived from simulations using molecular dynamics. Unlike the activation energy, the free-energy barrier includes the activation entropy and thus has been elusive to experimental determination for any kinetic process in solution.