Analysis of the stabilities of hexameric amyloid-β(1-42) models using discrete molecular dynamics simulations

Amyloid-β (Aβ) oligomers appear to play a pivotal role in Alzheimer's disease. A 42 residue long alloform, Aβ42, is closely related to etiology of the disease. In vitro results show evidences of hexamers; however structures of these hexamers have not been resolved experimentally. Here, we use discrete molecular dynamics (DMD) to analyze long duration stabilities of Aβ42 hexamer models developed previously in our lab. The hydrophobic core of these models is a six-stranded β-barrel with 3-fold radial symmetry formed by residues 30-40. This core is shielded from water by residues 1-28. The nine models we analyzed differ by the relative positions of the core β-strands, and whether the other segments surrounding the core contain α helices or β-strands. A model of an annular protofibril composed of 36 Aβ peptides was also simulated. Results of these model simulations were compared with results of aggregation simulations that started from six well separated random coils of Aβ42 and with simulations of two known β-barrel structures. These results can be categorized into three groups: stable models with properties similar or superior to those of experimentally determined β-barrel proteins, aggregation-prone models, and an amorphous aggregate from random coils. Conformations at the end of the simulation for aggregation-prone models have exposed hydrophobic core with dangling β-strands on the surface. Hydrogen bond patterns within the β-barrel were a critical factor for stability of the β-barrel models. Aggregation-prone conformations imply that the association of these hexamers may be possible, which could lead to the formation of larger assemblies.     

论(Cl_2BN_3)_n(n=1-4)簇合物

用密度泛函论B3LYP/6-311+G*法,计算(C1_2BN_3)_n(n=1-4)簇合物的结构和性质.发现,多聚体(C1_2BN_3)_n(n=2-4)的优化构型原来是由不同子体系的叠氮基α-N和B原子相连而形成的环状结构。几何参数的比较分析还发现N_α-B、N_α-N_β、N_β-N_Υ和B-Cl的键长与聚合度密切相关,环状构型中B-N_α-B键角总比N_α-B-N_α大。同时计算所有优化构型的振动频率,将其IR谱归类.通过热力学计算,发现簇合物的稳定性为3A>3B;4A>4B.由焓变可知,从单体形成二聚体于热力学不利,而形成最稳定三聚体和四聚体的温度分别达800K和500K仍是有利的.     

四氢萘微观结构的量子化学研究

为了研究氢化芳烃的微观结构,进一步认识和理解氢化芳烃在催化裂化过程中的反应特性。以四氢萘为模型化合物,利用基于密度泛函理论的量子化学从头计算方法,对四氢萘的几何结构和电子结构进行了系统研究,得到了四氢萘不同位置C-H键和C-C键的键长、键级、键能以及电子云密度、前线轨道分布等微观结构信息。发现四氢萘结构具有轴对称特性,苯环上的C-C键和C-H键要远比环烷环的C-C键和C-H键稳定。由于受苯环的影响,会使得其环烷环上不同位置的C-C键的键长、键级和键能均具有明显差异,也导致环烷环上不同位置C-H键的键长、键级和键能有较明显的差异,具体表现为:对C-C键而言,与苯环相连的C-C键的键长较短,键级较高,键能也明显较高,而苯环β位C-C键的键能则明显较低;对C-H键而言,与苯环β位环烷碳原子上的C-H键相比,苯环α位环烷碳原子上的C-H键的键能明显较低。电子云分布计算结果能够较好地给出的这些C-C键和C-H键结构特征差异的原因。前线轨道计算结果表明,在催化裂化过程中,苯环α位环烷碳原子上的C-H键和β位C-C键较易受到催化剂酸性中心的进攻,是酸催化反应的位点。这些计算结果对于认识与理解氢化芳烃的反应特性具有一定的基础性理论意义。     

煤表面对多个氧分子的多层吸附机理研究

应用密度泛函理论,在6-311水平上研究煤表面与氧的吸附作用,比较煤吸附5个氧分子,其表面与氧分子化学键的变化情况,吸附后氧分子的键变长,但不断裂,煤表面的变化很小,证明煤表面吸附5个氧分子是物理吸附,根据优化后的几何结构,证明还是多层吸附.其中侧链吸附的氧分子键长变化最大,由1.2582 A变为1.3244 A,说明侧链吸附的氧分子最活泼.从电荷集居数分析可知,原子中电子转移的多少与化学键的变化成正比,转移越多,化学键变化越大.煤表面与5个氧分子组成的吸附态中,氧分子的振动频率变小,计算其吸附能为409.68 kJ/mol.     

The solvent (water) and metal effects on HOMO-LUMO gaps of guanine base pair: A computational study

The most stable structures of guanine dimer and metal-mediated guanine base pair complexes were determined both in vacuum and solvent (water). Density functional theory (DFT) method is generally used in the calculations. The calculations of systems containing C, H, N, O is described by 6-311 + +G(d,p) basis set and LANL2DZ basis set is used for transition metals. Some geometrical parameters, the LUMO, HOMO energy levels and energy gaps of compounds are calculated. Hydrogen bond stabilization energies in dimer and charge transfer in metal complexes are also determined using NBO analysis. The solvent and metal effects on energy gaps of molecules are found. Cu-mediated guanine complex can be preferred for nanotechnological applications due to its good electronic properties.     

氨基酸His或二肽Cys-His共价修饰Fe(Ⅲ)-salophen的计算机模拟

通过比较天然血红素蛋白中血红素与多肽链进行共价连接的结构,我们对组氨酸(His)或二肽半胱氨酰-组氨酸(Cys-His)共价修饰人工配合物Fe(III)-salophen进行了计算机模拟,旨在为设计包含非天然辅基的金属蛋白分子提供有用的信息。修饰物采用分子力学MM 方法进行了分子构型优化,而且在最低能量构型的基础上,采用半经验量子化学ZINDO/1方法进行了单点计算。结果阐明,当His形成Fe(III)-salophen的第五轴向配体时,通过与His形成酰胺键进行共价修饰,引入丙酸根要比甲酸根使分子更加稳定;同时,在Fe(III)-salophem的位置a进行His或Cys-His共价修饰,均比在位置b进行修饰使分子更加稳定。此外,在所有修饰物分子中,最稳定的分子为:通过Cys与a位置所引入的乙烯基之间形成硫醚键的二肽Cys-His修饰物。这一结构与自然界中c型细胞色素一致。本研究提供了一些初步的理论研究结果,它能够指导功能性Fe(III)-salophen配合物的构建以及在人工金属蛋白设计中的应用。     

Solution conformation of phakellistatin 8 investigated by molecular dynamics simulations

Phakellistatin 8 is a cyclic decapeptide that inhibits cancer cell growth and has sequence and structure similar to antamanide. In molecular dynamics simulations of phakellistatin 8 in water, the decapeptide ring undergoes a conformational change from the saddle-like crystal structure to a more elongated conformation by a transition of the Tyr9 main chain from the alpha L to an extended structure. This is coupled to the loss of the NH9-O6 beta-turn hydrogen bond and the transient dissociation of the Pro7-Tyr9 side-chain packing. Furthermore, the water molecule acting as a transannular bridge forms an additional hydrogen bond with phakellistatin 8, namely with the NH group of Val5 besides those already present in the crystal structure, i.e., with the NH of Ile10 and the CO of Leu6. The alpha-turn hydrogen bond between the Phe4 amide hydrogen and the Ile10 carbonyl oxygen is always present. The solution conformations of the two cyclic decapeptides are similar, in particular in the region involving the NH4-O10 alpha turn of phakellistatin 8 and the NH5-O1 alpha turn of antamanide. The simulation results suggest that in aqueous solution the conformation of phakellistatin 8 is more extended than in the crystalline state, and on a nanosecond time scale phakellistatin 8 is more flexible than antamanide.     

Simulation of rowing in an optimization context

Competitive rowing requires efforts close to the physiological limits, where oxygen consumption is one main aspect. The rowing event also incorporates interactions between the rower, the boat and oars, and water. When the intention is to improve the performance, all these properties make the sport interesting from a scientific point of view, as the many variables influencing the performance form a complex optimization problem. Our aim was to formulate the rowing event as an optimization problem where the movement and forces are completely determined by the optimization, giving at least qualitative indications on good performance. A mechanical model of rigid links was used to represent rower, boat and oars. A multiple phase cyclic movement was simulated where catch slip, driving phase, release slip and recovery were modeled. For this simplified model, we demonstrate the influence of the stated mathematical cost function as well as a parameter study where the optimal performance is related to the planned average boat velocity. The results show qualitatively good resemblance to expected movements for the rowing event. An energy loss model in combination with case specific properties of rower capacities, boat properties, and rigging was required to draw qualitative practical conclusions about the rowing technique.     

Structural, electronic, and magnetic properties of heterofullerene C(58)Si with odd number of atoms and a near planar tetracoordinate Si atom

Density functional calculations and minimization techniques have been employed to characterize the structural and electronic properties of [5,6]-heterofullerene-C₅₈Si-C_2v. Since it has odd number of atoms and a near planar tetracoordinate Si atom on the skeleton of the cage, it has odd number of atoms assembling a cage and is a novel molecule. Vibrational frequencies of the molecule have been calculated at the B3LYP/6-31G* level of theory. The absence of imaginary vibrational frequency confirms that the molecule corresponds to a true minimum on the potential energy hypersurface. Sixteen ¹³C nuclear magnetic resonance (NMR) spectral signals of C₅₈Si are characterized, and its heat of formation was estimated in this work.     

C80-C90富勒烯结构与稳定性的理论研究

本文结合分子力学、半经验PM3和密度泛函(DFT)B3LYP方法对C80-C90的非分离五元环异构体和所有分离五元环异构体进行了理论研究。计算得到的B3LYP／6-31G的最低能量结构与文献报道一致。而且,对于C80-C90,并不存在一个特别稳定的非分离五元环异构体,分离五元环规则仍适用于富勒烯C80-C90。     

Intra-molecular electron communication,spectroscopic and conformational stability of the newly developed urethane modified polyetheramide coatings: Computational methods

There have been constant research efforts towards the development of new and thermally stable resins, containing properties to outdoor usage, such as high quality of adhesion, as well as resistance to water and acid, amongst others. In this computational study, the spectroscopic properties were calculated, also the intramolecular electronic communication, susceptibility, as well as conformational changes in two monomers of potential resins, namely Albiziabenth oil polyetheramide (ABOPEtA) and urethanated Albiziabenth oil polyetheramide (UABOPEtA), as well as their precursor, namely hydroxylethyl albiziabenth oil amide (HEABOA). Many of these computed properties clearly show that the urethane linkage group in UABOPEtA acts as a strong electron withdrawing group, consequently causing the rest of the molecule to be more nucleophilic. This leads to an increase in the stability of UABOPEtA, as compared the rest of the molecules, as evidenced by an increase in the intramolecular energy of interaction, as well as negative values of the polarizability exaltation index (Γ). Further UABOPEtA is also associated with higher non-linear optical properties, in terms of the hyperpolarizabilities (β) and increased aromaticity, than for molecules ABOPEtA and HEABOA. The conformational folding of molecule UABOPEtA is characterized by larger values of the bisphenol-A linkage bond angle C⋯C⋯C, contrary to the angle observed in molecule ABOPEtA. This is a direct effect of hiding the urethane unit in the cleft of the folded UABOPEtA, which clearly leads to an increase in the hydrophobicity of UABOPEtA.     

Driving mechanisms of CM-scaled PDMS boats of respective close and open reservoirs

A floating solid object may have a spontaneous motion on a water surface when a liquid, which has a surface tension lower than water, exits the solid object and has contact with water. This motion may be induced due to the difference between surface tensions of water and the liquid. In order to interpret this motion, it is important to know how the liquid exits the solid object. In this article, we reported in situ observation of exchange processes of water and isopropyl alcohol (IPA) inside both close and open reservoirs of cm-scaled polydimethylsiloxane (PDMS) boats. Based on this observation and force analysis, we interpreted driving mechanisms of these boats. We found that the exchange processes may be different in the PDMS boats of respective close and open reservoirs. The PDMS boat of a close reservoir might have a bubble trapped in its reservoir during the motion. This bubble slowed down the exiting process of the IPA from the reservoir, made the motion last longer, and enabled the boat to have a longer travel distance. Also, such a boat had gurgling-like motions (i.e., approximately periodic motions of deceleration and acceleration) after the majority of the IPA had exited the reservoir. The speeds of this boat had an order of 1?cm/s. On the other hand, neither bubbles nor gurgling-like phenomena were found in the motions of the PDMS boat of an open reservoir. The speeds of this boat were in the order of 1?cm/s as well. In addition, based on observed exiting processes of the IPA and experimentally determined speed-time relationships, we also set up a simple model to find force?Ctime relationships. Furthermore, we investigated the exiting process when the open reservoir of the cm-scaled PDMS boat was shallow. We found that, depending on the values of the height difference, h, between the bottom of the reservoir and the water surface outside the reservoir, three different phenomena might appear: (1) if h????1.33?mm, then the reservoir was empty at the end of the test and no water flowed into the reservoir during the test; (2) if 1.3?mm?<?h????2.3?mm, then the reservoir was empty at the end of the test while water flowed into the reservoir during the test; and (3) if 2.3?mm?<?h????3.0?mm, then the reservoir was filled by water at the end of the test. The difference in the filling results was induced by the interplay among Marangoni effect, free convection, and recovery of a hollow spot by surrounding water. The corresponding findings interpreted the exiting process of the IPA observed in the open reservoir of a mm-scaled SU-8 boat that we have previously developed, and also explained the filling result in the open reservoir of a PDMS boat.     

CH基团替代N对Nn（CH）8-nH8（n=0-7）结构与性质影响的理论研究

采用密度泛函理论的B3LYP方法在6-311++G^**基组水平上优化了,用等电子体-CH-基团逐个取代N8H8环状异构体中最稳定的分子构型中的N原子,得到32种N_n（CH）_8-nH₈（n=0-7）的异构体,应用自然键轨道理论NBO和分子中的原子理论AIM分析了这些化合物成键特征和相对稳定性,G3MP2方法计算了各异构体的能量及生成热。研究结果表明:N原子孤对电子到相邻的碳氮键的超共轭作用是影响碳氮键长变化的主要因素;随着等电子体-CH-基团取代分子中氮原子的个数的增加,分子的生产热逐渐减小,而分子的能量将逐渐升高,且有很好的线性相关性。     

Mg@C72 MNDO/d evaluation of the isomeric composition

Temperature development of the relative stabilities of isomers of Mg@C72 (which has not yet been isolated) is computed using the recently introduced MNDO/d method. Four isomers originally considered for the Ca@C72 case are treated: one isolated-pentagon-rule (IPR) structure, two structures with a pair of adjacent pentagons, and one cage with a heptagon. The IPR structure comes as the lowest in MNDO/d potential energy, being rather closely followed by the two structures with a pentagon-pentagon pair. On the other hand, the structure with a heptagon is located too high in potential energy to be of any experimental significance. The entropy contributions are evaluated by the MNDO/d-based partition functions so that the relative concentrations can be treated accordingly. The computations suggest that if Mg@C72 is isolated, it should be a mixture of either two or three isomers. The prediction depends on temperature prehistory. If preparation takes place at temperatures of approximately 1000 K, two isomers should be produced. If temperatures are increased to approximately 2000 K, there will already be three isomers with significant relative concentrations. The study supplies a further interesting example of the profound role of enthalpy-entropy interplay in stabilities of isomeric fullerenic structures.     

Application of the independent molecule model to the calculation of free energy and rigid-body motions of water heptamers and octamers

Stabilization of clusters of water heptamer and octamer in the gas phase is studied with the independent molecule model. As indicators of stabilization, the H-bonding strength, the H-bonding lifetime and the free energy are calculated. For both the heptamers and octamers, clusters with one oxygen-ring and some branching H-bonded waters are more stable than clusters with multi-oxygen-rings. Both the heptamer and octamer prefer a shape intermediate between planar and polyhedral; the branched waters are highly fluctuating and consequently contribute to increasing the entropy of the cluster. As the temperature increases from 0 to 300 K, the entropy contributes to the differentiation in free energy of the cluster geometries.     

C40H2各种可能异构体芳香性的研究

用键共振能(BRE)和拓扑共振能(TRE)方法,对由从富勒烯C_(40)(D_(5d))产生的富勒烯氢化物C_(40)H_2H所有可能异构体的芳香性进行了研究。研究了氢原子加成位置和芳香性之间的关系。计算结果表明,氢原子的加成位置与C_(40)(D_(5d))中各键的键共振能直接有关。在C_(40)(D_(5d))中C3类碳原子具有最大的反应活性。大部分C_(40)H_2异构体的芳香性高于C_(40)。用拓扑共振能方法得到的C_(40)H_2异构体的稳定性顺序与AM1和PM3半经验方法得到的稳定性顺序是一致的,用键共振能和拓扑共振能方法同样地能预测富勒烯氢化物的稳定性。     

Application of the independent molecule model to elucidate the dynamics of structure I methane hydrate: a second report

Two model systems of methane hydrate are constructed. One has a small cage surrounded by 12 large cages. The other has a large cage surrounded by four small cages and ten large cages. Three different H-bonding network patterns between waters are formed, and three random configurations of methane in each cage are chosen. A new method called the surface water fixed model is presented in which the energy minimum conformations for both model systems are preserved close to the X-ray crystallized structure. With normal mode analysis, we calculated frequencies of 2916.6 cm⁻¹ for a small cage at a centre, 2915.9 cm⁻¹ not at a centre, and 2911.7 cm⁻¹ for a large cage at a centre, and 2911.3 cm⁻¹ not at a centre. These frequencies are in moderate agreement with the corresponding Raman spectra, though not adequate. With our new method, however, it should be possible to improve agreement with the Raman spectra, if a model system vastly larger than the present model systems were constructed.     

DFT simulation towards evaluation the molecular structure and properties of the heterogeneous C16Mg8O8 nano–cage as selective nano–sensor for H2 and N2 gases

Adsorption of hydrogen (H₂) and nitrogen (N₂) molecules was analyzed on a new fullerene–like C₁₆Mg₈O₈ nano–cage, composed of magnesium, oxygen, and carbon, using density functional theory. A detailed analysis of the energy, geometry, and electronic structure of various H₂ and N₂ adsorptions on the cluster surface was performed. The adsorption energies of H₂ and N₂ were estimated to ranging from −0.16 to −0.52 eV, respectively. The most stable adsorption configurations were those in which the H or N atoms of the adsorbates were located near the Mg atom of the cluster surface at different sides. It was found that the heterogeneous C₁₆Mg₈O₈ nano–cluster selectively act against the H₂ and N₂ gaseous molecules. The electrical conductivity of the cluster, arising from HOMO/LUMO energy gap, was more sensitive to N₂ gaseous molecule rather than H₂ one, indicating that the heterogeneous C₁₆Mg₈O₈ nano–cage may be potential nano–sensor for N₂ molecule. These findings were specified by analyzing the characteristics in the electron density of states (DOS).     

Conformational Study of the Structure of dibenzo-18-crown-6. Comparison with 18-crown-6

We report for the first time the conformational analysis of dibenzo-18-crown-6, db18c6. The conformational search was carried out using the CONFLEX conformational search method of cyclic molecules. Energies were calculated for the low-lying predicted conformations at different levels of theory up to the G3MP2 level. At the G3MP2 level, the predicted ground state (GS) conformation was more stable than the experimental conformation by only 1.60 kcal/mol. Strong similarity was found between the GS structure and experimental conformations of db18c6 and 18-crown-6, 18c6. The GS and experimental conformations of db18c6 are non-planar. This allows db18c6 to exist in optically active enantiomers. Similar to 18c6, it was concluded that the db18c6 structure is stabilized by intramolecular hydrogen bond. We also performed the computations for the water and chloroform solution phase, where the same conformation was predicted as the GS conformation.     

碳原子簇Cn(n=2-20)的结构优化及构型转换

将并行快速退火演化算法结合Brenner势能函数用于小碳原子簇Cn(n=2—20)的结构优化，得到了最稳定构型：C2-C4为线型结构；C5-C17，为单环；C18和C19为类富勒烯的笼状结构；C30为最小的富勒烯。在Brenner势中使用了关于键级的修正项Fij以考虑成键轨道的非正常重叠和非、局域效应，研究了Fij项对碳原子簇键级以及结构转变产生的影响和原因，结果表明该修正项可以降低多环碳原子簇的键级，使得原子簇C18和C20的最稳定结构发生从多环到笼状的转变。