用于真实蛋白质结构预测的一种新的优化方法

用“相对熵”作为优化函数 ,提出了一个有效快速的折叠预测优化算法 .使用了非格点模型 ,预测只关心蛋白质主链的走向 .其中只用到了蛋白质主链上的两两连续的Cα 原子间的距离信息以及 2 0种氨基酸的接触势的一个扩展形式 .对几个真实蛋白质做了算法测试 ,预测的初始结构都为比较大的去折叠态 ,预测构象相对于它们天然结构的均方根偏差 (RMSD)为 5～ 7 .从原理上讲 ,该方法是对能量优化的改进 .     

比较与研究金属离子与三种蛋白的配位机理

本文通过测定牛血红蛋白、人血清蛋白、伴刀豆球蛋白Ａ与过渡态金属离子Ｃｒ（Ⅲ）、Ｆｅ（Ⅲ）在不同条件下的荧光强度变化来揭示蛋白质与金属离子形成络合物的配位点，从而确定所形成配合物的结构，并讨论了溶液ＰＨ值对蛋白质荧光强度的影响。另外，对金属离子与蛋白质体系进行了荧光偏振的研究。     

傅里叶变换红外光谱与圆二色光谱表征磷脂酶D二级结构的比较

报道了傅里叶变换红外光谱与圆二色光谱光学信息表征蛋白质二级结构的比较,研究表明傅里叶变换红外光谱与圆二色光谱光学信息表征蛋白质二级结构时,要注意缓冲体系的选择,磷酸盐缓冲液比醋酸盐缓冲液更适合使用,利用FTIR与CD光谱信息表征蛋白质二级结构,两者的数据吻合较好。     

旋转体系中湍流的LBM模拟

采用基于多松弛时间因子的格子Boltzmann方法对旋转体系中的湍流进行数值研究,考察Rossby数和Ekman数对湍流的影响,包括湍流能量及其耗散率、速度、涡结构及湍流的耗散尺度即Kolmorogov尺度和积分尺度等.研究表明,系统的旋转延缓了湍流能量的衰减速率,逐步破坏初始涡结构的均匀性,与旋转方向相反的涡逐步被抑制,并最终形成若干与旋转同向的涡柱.结果还表明,系统旋转越快,湍流的耗散尺度越小而积分尺度越大.     

蛋白质分子三维结构能量优化途径的选择

NMR方法是研究溶液中蛋白质的三维结构的重要手段,本文以BUSH ⅡA为例,对用度量矩阵距离几何法获得的初始三维结构进行了能量优化,主要探讨了蛋白质分子三维结构能量优化途径的选择问题.本文把优化过程分为三个阶段,分别采用不同的优化方式,使分子结构得到优化,对于分子量在8000左右的蛋白质而言,本方法能够获得较好符合核磁实验约束条件的分子低能构象.     

蛋白质分子链的非线性激发的孤子模型的一个改进解

通过仔细考察蛋白质分子链中体系运动方程的非线性项,得到了一个与通常非线性Schrdinger方程不同的修正的非线性Schrdinger方程,并求得了一个改进孤子解.     

天然色素苏木精与蛋白质纤维之间的相互作用

通过量子化学计算方法在密度泛函理论B 3LYP/6-31G*水平上对天然色素与蛋白质纤维之间的相互作用的相关性质进行了系统研究。对含有不同官能团的蛋白质纤维分子片段、苏木分子以及它们所构成的二元相互作用体系的几何构型进行了优化和频率分析;得到了含有不同官能团的蛋白质纤维分子片段和苏木分子之间的相互作用能和热力学数据,以及NBO电荷转移情况;通过AIM分析界定了含有不同官能团的蛋白质纤维分子片段和苏木分子之间的相互作用性质。计算结果表明,利用苏木对蛋白质纤维进行染色时,如果染液偏酸性,则苏木主要与蛋白质纤维中的氨基发生作用;如果染液偏碱性,则苏木主要与蛋白质纤维中的羧基发生作用。相对来说,在碱性条件下染色时,蛋白质纤维与苏木相互作用的结构更稳定。     

残留偶极耦合及其在蛋白质结构研究中的应用

近年来溶液中残留偶极耦合常数被用来获取生物大分子化学键之间相对取向等长程构象约束条件,用于计算或优化蛋白质及其复合物的三维空间结构. 介绍了用异核多维NMR技术测量残留偶极耦合常数的方法,及其在蛋白质结构计算中的一些应用：优化蛋白质溶液结构,评价蛋白质结构质量,确定蛋白质结构域取向,获取有关配体的构象和取向的信息,在缺乏NOE数据时构建蛋白质结构等.      

高压NMR在蛋白质结构和动力学研究中的应用

与温度一样,压力是基本的热力学变量.蛋白质在溶液中是多种构象的热力学平衡体.在不同的温度和压力等条件下,蛋白质包括折叠构象、变性构象以及各种中间体在内的不同构象的存在频率各不相同.当用压力作为扰动时,由于这些构象的偏摩尔体积不同,它们的存在频率便会因而发生变化,加压可将平衡向具有较小偏摩尔体积的方向移动.因此,利用高压核磁共振(NMR)技术,不仅可以研究高压对蛋白质结构和动力学的影响,还可以通过改变压力,在更为广泛的构象空间研究蛋白质结构和动力学.例如,利用平衡体系在加压时向体积小的构象方向移动这一特性,能够对在常压下因其存在频率低而难于检测、但在高压下因其体积小而存在频率增加了的构象进行深入研究,而这些构象往往与蛋白质的功能密切相关.该篇综述首先介绍了高压在蛋白质科学研究中的历史、有关概念和高压NMR技术;其次,结合实例,阐述高压NMR技术在蛋白质结构、折叠以及动力学研究中的应用;最后,对高压NMR技术在蛋白质研究中的应用前景进行展望.     

葛根素与乙酰胆碱酯酶作用的分子动力学模拟

旨在阐明葛根素与乙酰胆碱酯酶(AChE)的分子作用机制,并为基于葛根素的类似物的AChE抑制剂的研发提供参考.运用AutoDock 4.2进行葛根素与AChE的分子对接,采用YASARA进行分子动力学模拟,利用MMPBSA.py模块计算复合体系的结合自由能,分析氨基酸的能量贡献.结果显示,葛根素与AChE对接体系含有4个氢键,2个π-π键. 5 ns后,体系均方根偏差(RMSD)趋于平衡,体系结合自由能为-18.19 kcal/mol.促体系结合的主要作用力是范德华力、静电作用力,非溶剂化能是主要的结合阻力.能量贡献最大的残基依次为Asn533、Lys530、Ala534、Pro529.这些研究为新型抑制剂的研发提供理论参考.     

The fumarate sensor DcuS: progress in rapid protein fold elucidation by combining protein structure prediction methods with NMR spectroscopy

We illustrate how moderate resolution protein structures can be rapidly obtained by interlinking computational prediction methodologies with un- or partially assigned NMR data. To facilitate the application of our recently described method of ranking and subsequent refining alternative structural models using unassigned NMR data [Proc. Natl. Acad. Sci. USA 100 (2003) 15404] for such "structural genomics"-type experiments it is combined with protein models from several prediction techniques, enhanced to utilize partial assignments, and applied on a protein with an unknown structure and fold. From the original NMR spectra obtained for the 140 residue fumarate sensor DcuS, 1100 1H, 13C, and 15N chemical shift signals, 3000 1H-1H NOESY cross peak intensities, and 209 backbone residual dipolar couplings were extracted and used to rank models produced by de novo structure prediction and comparative modeling methods. The ranking proceeds in two steps: first, an optimal assignment of the NMR peaks to atoms is found for each model independently, and second, the models are ranked based on the consistency between the NMR data and the model assuming these optimal assignments. The low-resolution model selected using this ranking procedure had the correct overall fold and a global backbone RMSD of 6.0 angstrom, and was subsequently refined to 3.7 angstrom RMSD. With the incorporation of a small number of NOE and residual dipolar coupling constraints available very early in the traditional spectral assignment process, a model with an RMSD of 2.8 angstrom could rapidly be built. The ability to generate moderate resolution models within days of NMR data collection should facilitate large scale NMR structure determination efforts.     

盐离子对蛋白质带电特性的影响

本文应用分子理论,研究盐离子对蛋白质带电特性的影响,理论模型考虑蛋白质与阴离子的结合作用。研究发现,由于蛋白质与阴离子的结合,距离蛋白质表面附近处的阴离子被吸附在了蛋白质表面,在距离蛋白质表面附近区域,阴离子分布较少。通过计算体系中的静电势,我们发现,在距离蛋白质表面附近,静电势呈现了较大的负值,带正电荷的阳离子感受到静电吸引,会出现在距离蛋白质表面附近的区域,这会使得在距离蛋白质表面附近的区域,阳离子数目增多。这样,在不同阴离子浓度、以及阴离子与蛋白质不同结合能条件下,阴离子会在不同程度上影响蛋白质的带电特性、影响体系中的静电特性。通过考察不同结合能条件下,蛋白质表面电荷面密度随阴离子浓度的变化关系还发现,较大的结合能会使得阴离子与蛋白质结合增快,蛋白质表面会呈现从正电荷态向负电荷态的转变。理论结果符合实验观测,由此表明,盐离子与蛋白质的结合导致蛋白质表面带电特性的改变,是盐离子影响蛋白质带电特性的本质。     

Application of multi-phase particle swarm optimization technique to inverse radiation problem

The multi-phase particle swarm optimization (MPPSO) technique is applied to the inverse radiation problem in the present paper. The directional radiative intensities are served as the measurement data to estimate the radiative source term, optical thickness, scattering albedo, and phase function in one-dimensional semitransparent plane-parallel media by the inverse simulation. To check the performance and accuracy in retrieval, a comparison is presented between three PSO methods, i.e. the MPPSO, the standard PSO, and the Stochastic PSO. The results confirm the potential of the proposed approach MPPSO and show its effectiveness and superiority over the other two PSO algorithms. Furthermore, the effects of swarm size, searching space, phase change frequency, and velocity-reinitializing frequency on the convergence velocity and computational accuracy of MPPSO are also investigated.     

Particle swarm modeling of vapor-liquid equilibrium data of binary systems containing CO<Subscript>2</Subscript> + imidazolium ionic liquids based on bis[(trifluoromethyl)sulfonyl]imide anion

Based on particle swarm optimization (PSO), a thermodynamic modeling for the vapor-liquid equilibrium of binary mixtures of carbon dioxide with ionic liquids is presented. The Peng-Robinson equation of state with the Wong-Sandler mixing rules is used to evaluate the fugacity coefficient of the systems. Simulations are carried out in five systems containing 1-alkyl-3-methylimidazolium ionic liquids based on bis[(trifluoromethyl)sulfonyl]imide anion. Then, PSO algorithm was used to minimize the difference between calculated and experimental bubble pressure, and calculate the interaction parameters and the excess Gibbs free energy for all systems used. The results show that the bubble pressures were correlated with low deviations between experimental and calculated values. These deviations show that the PSO algorithm is the preferable method to optimize the interaction parameters of the phase equilibria of binary systems of supercritical carbon dioxide with ionic liquids, and can be used for other similar systems.     

一种基于多准则决策和PSO-LM混合优化算法的多峰Brillouin散射谱的特征提取方法

采用传统方法对多峰Brillouin散射谱进行拟合的过程中,通常是以谱线最大功率点为基准的,却忽略了其他比该点小但却是极值的功率点。这样获得的拟合曲线通常只有一个峰值,相当于把除最高峰之外还有多个小峰的多峰Brillouin散射谱进行了简化,导致大量有用信息的丢失。为了提高Brillouin散射谱的特征提取精度,提出了一种基于MCDM和PSO-LM混合优化算法的多峰Brillouin散射谱特征提取方法(MCDM-PSO-LM)。MCDM可以识别和准确定位多峰Brillouin散射谱的各个波峰和波谷;PSO-LM混合优化算法可以实现分别对各个波峰和波谷的曲线进行拟合并找到每一个波峰的中心频率,该算法既克服了PSO算法过早收敛于局部极值和LM算法依赖初值的问题,又可以将PSO算法的全局搜索能力和LM算法的局部收敛能力结合在一起。较传统算法而言,MCDM-PSO-LM算法保证了对最优值求解的速度和精度,提高了运算能力,使解析解最大限度地接近最优值。分别在不同信噪比和不同线宽条件下进行仿真验证,频移和温度误差分析结果表明,MCDM-PSO-LM方法可以对多峰Brillouin散射谱的各个波峰与波谷进行准确定位,可用于多峰Brillouin散射谱的特征提取,识别效果明显强于传统算法,提高了信息分析的准确性。     

The Interaction of a New Schiff Base Ligand with Human Serum Albumin: Molecular Docking and Molecular Dynamics Simulation Studies

The interaction of a new heterocyclic Schiff base bearing pyridine and pyrimidine cycles, with human serum albumin (HSA) using molecular docking and molecular dynamics simulation methods was examined. Molecular docking studies showed that the ligand was bonded to the IB domain of the protein. It was found that there was one hydrogen bond interaction between HSA and the ligand. The standard Gibbs free energy for binding of the ligand to HSA was calculated as ?9.63 kcal.mol^?1. The results of the molecular dynamics simulation showed that the root mean square deviation (RMSD) of the non-liganded HSA and the HSA–ligand complex reached equilibration after 1000 ps. The study of the radius of gyration revealed that there was a conformational change when the HSA–ligand complex was formed. Finally, analyzing the RMS fluctuations (RMSF) suggested that the structure of the ligand binding site remained approximately rigid during the simulation.     

Automatic assignment of NOESY cross peaks and determination of the protein structure of a new world scorpion neurotoxin using NOAH/DIAMOD

The 3D NMR structures of the scorpion neurotoxin, CsE-v5, were determined from the same NOESY spectra with NOAH/DIAMOD, an automated assignment and 3D structure calculation software package, and with a conventional manual assignment combined with a distance geometry/simulated annealing (X-PLOR) refinement method. The NOESY assignments and the 3D structures obtained from the two independent methods were compared in detail. The NOAH/DIAMOD program suite uses feedback filtering and self-correcting distance geometry methods to automatically assign NOESY spectra and to calculate the 3D structure of a protein. NOESY cross peaks were automatically picked using a standard software package and combined with 74 manually assigned NOESY peaks to start the NOAH/DIAMOD calculations. After 63 NOAH/DIAMOD cycles, using REDAC procedures in the last 8 cycles, and final FANTOM constrained energy minimization, a bundle of 20 structures with the smallest target functions has a RMSD of 0.81 A for backbone atoms and 1.11 A for all heavy atoms to the mean structure. Despite some missing chemical shifts of side chain protons, 776 (including 74 manually assigned) of 1130 NOE peaks were unambiguously assigned, 150 peaks have more than one possible assignment compatible with the bundle structures, and only 30 peaks could not be assigned within the given chemical shift tolerance ranges in either the D1 or the D2 dimension. The remaining 174, mainly weak NOE peaks were not compatible with the final 20 best bundle structures at the last NOAH/DIAMOD cycle. The automatically determined structures agree well with the structures determined independently using the conventional method and the same NMR spectra, with the mean RMSD in well-defined regions of 0.84 A for bb and 1.48 A for all heavy atoms from residues 2-5, 18-26, 32-36, and 39-45. This study demonstrates the potential of the NOAH/DIAMOD program suite to automatically assign NMR data for proteins and determine their structure.     

基于PSO-DE算法的污水处理优化控制研究

针对污水处理系统能耗过大,变量多,非线性和滞后严重等特点造成的控制困难问题,提出了基于改进型粒子群的算法的优化控制。粒子群算法具有自适应控制,全局搜索等优点但本身存在早熟收敛及在进化后期收敛速度慢等缺点,通过优势互补思想引入差分进化算法,新算法结合两者优势有效提高粒子在全局的寻优效率,建立对应的混合算法优化模型,并与普通粒子群算法优化进行比较,结果证明了该算法在保证出水水质的前提下做到降低能耗。     

Grain Boundary Diffusion in Polycrystalline Ferrites with Different Intergranular Potential Barrier

Using the method of layer-by-layer measurements of the electrical conductivity activation energy, an investigation is performed of grain-boundary diffusion of oxygen in polycrystalline Li–Ti-ferrites in the range of temperatures 873–1073 K. A correlation relation is established between the value of the intergranular potential barrier and the parameters of grain-boundary diffusion of oxygen in polycrystalline ferrites. An increase in this value gives rise to a growth in the diffusion activation energy. The grain-boundary diffusion coefficient increases with the value of the intergranular potential barrier.     

固体的热膨胀系数

 本文由Grüneisen第二定则出发，采用普适能量函数作为原子间相互作用势能函数，计算立方晶体金属元素和几种NaCl型结构的碱卤晶体的线膨胀系数。计算值与实验值符合得很好。