人SEPT9蛋白同源建模和活性位点分析

利用生物信息学在线软件预测了人SETP 9蛋白质的二级结构和模体信息,同时对其三级结构进行同源建模和模建结果质量评价,其次预测了该蛋白质的活性位点信息,旨在从蛋白质序列特征和分子结构水平理解其在人类生理病理过程中的作用.结果表明,模建的SEPT 9蛋白结构品质较高,具有7段α-螺旋和2组β-折叠结构,是一个典型的α/β类蛋白,表面呈弱正电势分布;人SEPT 9蛋白具有8个不同模体,可能参与不同生化反应或执行不同的功能.搜寻获得了人SEPT 9蛋白配基结合位点有10个,其中位点1可能是该蛋白的活性位点.这些研究结果对理解人SEPT 9蛋白功能以及配基结合位点定位非常重要,也为针对SEPT 9蛋白的分子对接和药物从头设计提供了理论基础.     

Design and optimization of a linker for fusion protein construction

Bivalent, bispecific single-chain antibody fusion protein construction appears to be a promising tool for tumor therapy. One of its drawbacks is that the function and activity of the fusion proteins have varied affinity and/or anti-tumor activity compared with the original molecules from which they are derived. A more optimized linker for fusion proteins would confer more favorable biological activities upon bispecific single-chain antibodies. Thus, it is critical to design and optimize an inter-peptide linker. With different functional domains and optimized linkers, fusion proteins provide a solid base for targeted immune therapy for malignancies. In this paper, we review the inter-peptide linker studies and the design of an optimized linker using genetic algorithms. The spatial structure of the fusion protein can be predicted by using genetic and bioinformatics research. Based on current research, the future focus will be on different correlation models to perform simulations of spatial structures and drug molecule design.     

Self-assembly of amphiphilic dendritic dipeptides into helical pores

Natural pore-forming proteins act as viral helical coats and transmembrane channels, exhibit antibacterial activity and are used in synthetic systems, such as for reversible encapsulation or stochastic sensing. These diverse functions are intimately linked to protein structure. The close link between protein structure and protein function makes the design of synthetic mimics a formidable challenge, given that structure formation needs to be carefully controlled on all hierarchy levels, in solution and in the bulk. In fact, with few exceptions, synthetic pore structures capable of assembling into periodically ordered assemblies that are stable in solution and in the solid state have not yet been realized. In the case of dendrimers, covalent and non-covalent coating and assembly of a range of different structures has only yielded closed columns. Here we describe a library of amphiphilic dendritic dipeptides that self-assemble in solution and in bulk through a complex recognition process into helical pores. We find that the molecular recognition and self-assembly process is sufficiently robust to tolerate a range of modifications to the amphiphile structure, while preliminary proton transport measurements establish that the pores are functional. We expect that this class of self-assembling dendrimers will allow the design of a variety of biologically inspired systems with functional properties arising from their porous structure.     

Catalytic Peptide Dendrimers as Artificial Proteins： Functional Selection and Optimization from Combinatorial Libraries

1 Introduction In de novo protein design one attempts to create artificial proteins with defined structure and function from first principles, usually with the help of trial-and-error procedures that scan a large number of possible amino acid sequences. Our approach to de novo protein design is based on peptide dendrimers. Dendrimers are tree-like structures that adopt a globular or disk-shaped structure as a consequence of topology rather than folding. Our peptide dendrimers are obtained by a…     

Structure-based design of non-natural amino-acid inhibitors of amyloid fibril formation

Many globular and natively disordered proteins can convert into amyloid fibrils. These fibrils are associated with numerous pathologies as well as with normal cellular functions, and frequently form during protein denaturation. Inhibitors of pathological amyloid fibril formation could be useful in the development of therapeutics, provided that the inhibitors were specific enough to avoid interfering with normal processes. Here we show that computer-aided, structure-based design can yield highly specific peptide inhibitors of amyloid formation. Using known atomic structures of segments of amyloid fibrils as templates, we have designed and characterized an all-D-amino-acid inhibitor of the fibril formation of the tau protein associated with Alzheimer's disease, and a non-natural L-amino-acid inhibitor of an amyloid fibril that enhances sexual transmission of human immunodeficiency virus. Our results indicate that peptides from structure-based designs can disrupt the fibril formation of full-length proteins, including those, such as tau protein, that lack fully ordered native structures. Because the inhibiting peptides have been designed on structures of dual-β-sheet 'steric zippers', the successful inhibition of amyloid fibril formation strengthens the hypothesis that amyloid spines contain steric zippers.     

Rational screenning in combinatorial peptide libraries of protein functional loop

Redesigning the sequences of protein loops is a frequent practice in protein design. Based on the new results of protein loop database analysis, a rational computer simulation strategy is proposed to obtain functional proteins, which exploits a fast and accurate program to calculate the protein loop conformation, and at the same time, combines molecular docking method with combinatorial chemistry strategy to screen the combinatorial peptide library of protein loops. A characteristic of this method is that it separates the conformation computation of backbone from that of side chain and incorporates side chain growth into the docking procedure and therefore greatly reduces the computation by converting the huge computation on explosive conformations to relatively small computation on limited canonical backbone structures and side chain growth. This method can be practically used in screening combinatorial peptide libraries of protein loops.     

Hierarchical self-assembly of DNA into symmetric supramolecular polyhedra

DNA is renowned for its double helix structure and the base pairing that enables the recognition and highly selective binding of complementary DNA strands. These features, and the ability to create DNA strands with any desired sequence of bases, have led to the use of DNA rationally to design various nanostructures and even execute molecular computations. Of the wide range of self-assembled DNA nanostructures reported, most are one- or two-dimensional. Examples of three-dimensional DNA structures include cubes, truncated octahedra, octohedra and tetrahedra, which are all comprised of many different DNA strands with unique sequences. When aiming for large structures, the need to synthesize large numbers (hundreds) of unique DNA strands poses a challenging design problem. Here, we demonstrate a simple solution to this problem: the design of basic DNA building units in such a way that many copies of identical units assemble into larger three-dimensional structures. We test this hierarchical self-assembly concept with DNA molecules that form three-point-star motifs, or tiles. By controlling the flexibility and concentration of the tiles, the one-pot assembly yields tetrahedra, dodecahedra or buckyballs that are tens of nanometres in size and comprised of four, twenty or sixty individual tiles, respectively. We expect that our assembly strategy can be adapted to allow the fabrication of a range of relatively complex three-dimensional structures.     

Assessment of protein models with three-dimensional profiles.

As methods for determining protein three-dimensional (3D) structure develop, a continuing problem is how to verify that the final protein model is correct. The revision of several protein models to correct errors has prompted the development of new criteria for judging the validity of X-ray and NMR structures, as well as the formation of energetic and empirical methods to evaluate the correctness of protein models. The challenge is to distinguish between a mistraced or wrongly folded model, and one that is basically correct, but not adequately refined. We show that an effective test of the accuracy of a 3D protein model is a comparison of the model to its own amino-acid sequence, using a 3D profile, computed from the atomic coordinates of the structure 3D profiles of correct protein structures match their own sequences with high scores. In contrast, 3D profiles for protein models known to be wrong score poorly. An incorrectly modelled segment in an otherwise correct structure can be identified by examining the profile score in a moving-window scan. The accuracy of a protein model can be assessed by its 3D profile, regardless of whether the model has been derived by X-ray, NMR or computational procedures.     

相邻结构减震优化分析

利用阻尼器连接相邻结构可减小结构地震反应,阻尼器参数的确定是减震设计的关键。根据随机振动理论,在白噪声激励下,以相邻结构的自振频率比、质量比为参数,推导了结构位移反应均方值与连接阻尼参数的关系式,分析了相邻结构的地震反应与频率比、质量比以及连接阻尼比的变化规律,从而得到了连接阻尼器的优化设计参数。最后在El Centro波、Taft波及人工波激励下,对比分析了某相邻10层建筑结构有连接和无连接时的地震反应,结果表明粘滞阻尼器连接相邻结构具有较好的减震效果。本文分析方法可供相邻结构减震设计参考。     

MATLAB在混凝土结构优化设计教学中的运用

借助MATLAB软件对混凝土结构受弯构件优化设计进行了研究.建立了混凝土结构受弯构件优化设计的数学模型;编写了混凝土结构受弯构件优化设计程序;计算分析表明:计算结果满足混凝土结构设计规范的要求.     

Design principles of a bacterial signalling network

Cellular biochemical networks have to function in a noisy environment using imperfect components. In particular, networks involved in gene regulation or signal transduction allow only for small output tolerances, and the underlying network structures can be expected to have undergone evolution for inherent robustness against perturbations. Here we combine theoretical and experimental analyses to investigate an optimal design for the signalling network of bacterial chemotaxis, one of the most thoroughly studied signalling networks in biology. We experimentally determine the extent of intercellular variations in the expression levels of chemotaxis proteins and use computer simulations to quantify the robustness of several hypothetical chemotaxis pathway topologies to such gene expression noise. We demonstrate that among these topologies the experimentally established chemotaxis network of Escherichia coli has the smallest sufficiently robust network structure, allowing accurate chemotactic response for almost all individuals within a population. Our results suggest that this pathway has evolved to show an optimal chemotactic performance while minimizing the cost of resources associated with high levels of protein expression. Moreover, the underlying topological design principles compensating for intercellular variations seem to be highly conserved among bacterial chemosensory systems.     

永磁同步电机的结构与其电磁参数关系分析

永磁同步电机的结构多种多样 ,磁场复杂 ,在电机的设计和仿真时 ,电磁参数不易得到。论文提出一种新的方法 ,从电机电磁场的角度 ,研究电磁参数和电机结构的关系。在永磁同步电机的设计和仿真时 ,直接根据具体电机结构调入所需电磁参数 ,不但缩短了仿真程序的开发周期 ,而且能进行多种结构电机的设计 ,增加了程序的通用性。另外 ,从电磁场的角度直接计算电磁参数 ,保证了参数的精确性。针对内置径向式永磁同步电机 ,研究了电磁参数与其结构关系 ,并将所得参数用于电机的设计和仿真。仿真和试验结果表明该方法能快速精确地设计永磁同步电机     

渤海经济型抗冰结构全寿命设计框架

渤海经济型抗冰结构基本设计中存在很多缺陷,在服役期间承受着各种风险,必须从以往重点关注平台施工完成状态拓展到规划、设计、施工、管养等结构的整个寿命周期过程．提出了渤海经济型抗冰结构的全寿命设计框架,包括选型设计、性能设计、管养设计．通过对现有规范要求及基本设计的研究,突出结构抗冰性能要求,采用合理的管养,对全寿命成本效率优化设计框架进行评价,设计结果可使寿命周期内结构风险最低．     

大空间中庭及周边房间烟气运动和消防设计

采用数值模拟的方法,对大空间中庭结构内火灾及周边房间火灾的烟气运动情况进行了分析。着重分析了周边房间发生火灾后烟气及热羽流对上层房间的影响和烟气在中庭顶部的积聚和沉降情况。分析结果表明,在大空间内合理设置排烟系统对保证其消防安全至关重要;在大空间中庭内部排烟充分的情况下,可将大空间中庭作为与之相通的建筑结构的蓄烟空间和排烟途径,在其消防设计中可对中庭设置普通开口而不设置机械排烟系统。分析结果为大空间中庭及其周边房间的消防安全设计与评估提供参考。     

概念设计中机器学习技术的运用

设计中开发计算理论的一个挑战是必须能支持计算机的有效运用，这一机制允许从设计专家那儿或设计样例中取得产生，累加和转换的设计知识。而其中的一个方法是把机器学习机制综合成基于知识的支持系统，以模拟设计过程初级阶段，使设计成为一个增加和诱导学习的过程。模拟的需要产生于在不同的提取阶段获取，提炼和转移设计知识的需求，从而使得能轻而易举的熟练操作。在设计中，现有的知识产生于过去的设计解决方案，而过去的解决方案提供的反馈信息能更新和提高设计理论知识基础。但是，没有学习接受能力，设计系统不能反映设计家们在这一领域的成长经历，也不能反映设计家们从以往设计案例中提取知识的能力。在此提出了方案设计和效力评价中的三种方法。     

智能结构设计的灵敏度分析

由直接求导法导出特征值、特征向量和响应的一阶导数公式，进而将其表示成有限元摄动形式，建立了智能结构设计灵敏度分析的有限元摄动法．此方法既可避免直接对质量阵和刚度阵求导，使质量和刚度阵不能表示成设计变量显式时，仍能很方便地进行灵敏度分析，又可直接在大型结构分析程序上实施．文中给出的算例说明了方法的有效性及应用价值．     

论第三代结构设计理论

工程结构的第三代设计理论已经初具雏形、呼之欲出.从对结构设计理论的两个基本维度的分析入手,概略论述了第一代、第二代结构设计理论的发展历程.在此基础上,指出了第二代结构设计理论的局限性与基本矛盾,分析了第三代结构设计理论应该具有的基本特征,论述了其理论基础和基本构架.对为完整建立第三代结构设计理论尚需展开的研究做出了主题描述.     

Folding-driven synthesis of oligomers.

The biological function of biomacromolecules such as DNA and enzymes depends on their ability to perform and control molecular association, catalysis, self-replication or other chemical processes. In the case of proteins in particular, the dependence of these functions on the three-dimensional protein conformation is long known and has inspired the development of synthetic oligomers and polymers with the capacity to fold in a controlled manner, but it remains challenging to design these so-called 'foldamers' so that they are capable of inducing or controlling chemical processes and interactions. Here we show that the stability gained from folding can be used to control the synthesis of oligomers from short chain segments reversibly ligated through an imine metathesis reaction. That is, folding shifts the ligation equilibrium in favour of conformationally ordered sequences, so that oligomers having the most stable solution structures form preferentially. Crystallization has previously been used to shift an equilibrium in order to indirectly influence the synthesis of small molecules, but the present approach to selectively prepare macromolecules with stable conformations directly connects folding and synthesis, emphasizing molecular function rather than structure in polymer synthesis.     

直线型失谐周期结构中局部化现象的研究进程和现状

周期结构在工程中有很多应用实例.失谐可使周期结构的力学特性产生本质变化,产生振动局部化现象.局部化破坏了周期结构模态的规则性,在外激励下会使结构某些部位的响应幅值过大,产生能量积聚,甚至导致结构发生疲劳破坏,因此,分析失谐周期结构中振动和能量的传播方式与规律,具有重要的理论与实际意义.现主要针对失谐周期结构中的结构动力特性及直线型失谐周期结构的一些研究现状做一些概要的介绍.     

采用遗传算法的PDC钻头侧向力平衡优化设计

PDC钻头侧向力平衡优化设计时，散布式钻头与刀翼式钻头相比优化对象数目大幅度增加，最优解搜索空间成指数增长。为了突破PDC钻头结构对侧向力平衡优化设计的限制，采用比率选择、单点交叉、均匀变异和代沟操作等多项技术，利用遗传算法建立了PDC钻头侧向力平衡优化设计方法。利用该方法对刀翼式和散布式PDC钻头进行了侧向力平衡优化设计，优化后侧向力与钻压比值小于1／1000，算法收敛速度快，且算法复杂度受刀翼数量和切削齿数量影响较小。