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1.
Designing protein molecules that will assemble into various kinds of ordered materials represents an important challenge in nanotechnology. We report the crystal structure of a 12-subunit protein cage that self-assembles by design to form a tetrahedral structure roughly 16 nanometers in diameter. The strategy of fusing together oligomeric protein domains can be generalized to produce other kinds of cages or extended materials. 相似文献
2.
Fleishman SJ Whitehead TA Ekiert DC Dreyfus C Corn JE Strauch EM Wilson IA Baker D 《Science (New York, N.Y.)》2011,332(6031):816-821
We describe a general computational method for designing proteins that bind a surface patch of interest on a target macromolecule. Favorable interactions between disembodied amino acid residues and the target surface are identified and used to anchor de novo designed interfaces. The method was used to design proteins that bind a conserved surface patch on the stem of the influenza hemagglutinin (HA) from the 1918 H1N1 pandemic virus. After affinity maturation, two of the designed proteins, HB36 and HB80, bind H1 and H5 HAs with low nanomolar affinity. Further, HB80 inhibits the HA fusogenic conformational changes induced at low pH. The crystal structure of HB36 in complex with 1918/H1 HA revealed that the actual binding interface is nearly identical to that in the computational design model. Such designed binding proteins may be useful for both diagnostics and therapeutics. 相似文献
3.
Characterization of a helical protein designed from first principles 总被引：34，自引：0，他引：34
The question of how the primary amino acid sequence of a protein determines its three-dimensional structure is still unanswered. One approach to this problem involves the de novo design of model peptides and proteins that should adopt desired three-dimensional structures. A systematic approach was aimed at the design of a four-helix bundle protein. The gene encoding the designed protein was synthesized and the protein was expressed in Escherichia coli and purified to homogeneity. The protein was shown to be monomeric, highly helical, and very stable to denaturation by guanidine hydrochloride (GuHCl). Thus a globular protein has been designed that is capable of adopting a stable, folded structure in aqueous solution. 相似文献
4.
Traditionally, access to structurally defined complex carbohydrates has been very laborious. Although recent advancements in solid-phase synthesis have made the construction of complex oligosaccharides less tedious, a high level of technical expertise is still necessary to obtain the desired structures. We describe the automated chemical synthesis of several oligosaccharides on a solid-phase synthesizer. A branched dodecasaccharide was synthesized through the use of glycosyl phosphate building blocks and an octenediol functionalized resin. The target oligosaccharide was readily obtained after cleavage from the solid support. Access to certain complex oligosaccharides now has become feasible in a fashion much like the construction of oligopeptides and oligonucleotides. 相似文献
5.
Nucleation, growth, and dissolution of crystals have been studied by stereochemical approach involving molecular recognition at interfaces. A methodology is described for using ;;tailor-made' additives designed to interact stereospecifically with crystal surfaces during growth and dissolution. This procedure was instrumental in controlling crystal morphology and in revising the concept of the structure and symmetry of solid solutions. Consequently, it was applied to the transformation of centrosymmetric single crystals into solid solutions with polar arrangement displaying second-harmonic generation and to the performance of asymmetric synthesis of guest molecules inside centrosymmetric host crystals. The method has led to a discovery of a new ;;relay' mechanism explaining the effect of solvent on crystal growth. Finally, it allowed for the design of auxiliary molecules that act as promoters or inhibitors of crystal nucleation that can be used to resolve enantiomers and crystallize desired polymorphs. 相似文献
6.
Interpenetration (catenation) has long been considered a major impediment in the achievement of stable and porous crystalline structures. A strategy for the design of highly porous and structurally stable networks makes use of metal-organic building blocks that can be assembled on a triply periodic P-minimal geometric surface to produce structures that are interpenetrating-more accurately considered as interwoven. We used 4,4',4"-benzene-1,3,5-triyl-tribenzoic acid (H(3)BTB), copper(II) nitrate, and N,N'-dimethylformamide (DMF) to prepare Cu(3)(BTB)(2)(H(2)O)(3).(DMF)(9)(H(2)O)(2) (MOF-14), whose structure reveals a pair of interwoven metal-organic frameworks that are mutually reinforced. The structure contains remarkably large pores, 16.4 angstroms in diameter, in which voluminous amounts of gases and organic solvents can be reversibly sorbed. 相似文献
7.
Rational design of enzymes is a stringent test of our understanding of protein chemistry and has numerous potential applications. Here, we present and experimentally validate the computational design of enzyme activity in proteins of known structure. We have predicted mutations that introduce triose phosphate isomerase activity into ribose-binding protein, a receptor that normally lacks enzyme activity. The resulting designs contain 18 to 22 mutations, exhibit 10(5)- to 10(6)-fold rate enhancements over the uncatalyzed reaction, and are biologically active, in that they support the growth of Escherichia coli under gluconeogenic conditions. The inherent generality of the design method suggests that many enzymes can be designed by this approach. 相似文献
8.
Azoitei ML Correia BE Ban YE Carrico C Kalyuzhniy O Chen L Schroeter A Huang PS McLellan JS Kwong PD Baker D Strong RK Schief WR 《Science (New York, N.Y.)》2011,334(6054):373-376
The manipulation of protein backbone structure to control interaction and function is a challenge for protein engineering. We integrated computational design with experimental selection for grafting the backbone and side chains of a two-segment HIV gp120 epitope, targeted by the cross-neutralizing antibody b12, onto an unrelated scaffold protein. The final scaffolds bound b12 with high specificity and with affinity similar to that of gp120, and crystallographic analysis of a scaffold bound to b12 revealed high structural mimicry of the gp120-b12 complex structure. The method can be generalized to design other functional proteins through backbone grafting. 相似文献
9.
Mussel-inspired surface chemistry for multifunctional coatings 总被引：2，自引：0，他引：2
We report a method to form multifunctional polymer coatings through simple dip-coating of objects in an aqueous solution of dopamine. Inspired by the composition of adhesive proteins in mussels, we used dopamine self-polymerization to form thin, surface-adherent polydopamine films onto a wide range of inorganic and organic materials, including noble metals, oxides, polymers, semiconductors, and ceramics. Secondary reactions can be used to create a variety of ad-layers, including self-assembled monolayers through deposition of long-chain molecular building blocks, metal films by electroless metallization, and bioinert and bioactive surfaces via grafting of macromolecules. 相似文献
10.
We used phase models to describe and tune complex dynamic structures to desired states; weak, nondestructive signals are used to alter interactions among nonlinear rhythmic elements. Experiments on electrochemical reactions on electrode arrays were used to demonstrate the power of mild model-engineered feedback to achieve a desired response. Applications are made to the generation of sequentially visited dynamic cluster patterns similar to reproducible sequences seen in biological systems and to the design of a nonlinear antipacemaker for the destruction of pathological synchronization of a population of interacting oscillators. 相似文献
11.
Wikoff WR Liljas L Duda RL Tsuruta H Hendrix RW Johnson JE 《Science (New York, N.Y.)》2000,289(5487):2129-2133
The crystal structure of the double-stranded DNA bacteriophage HK97 mature empty capsid was determined at 3.6 angstrom resolution. The 660 angstrom diameter icosahedral particle contains 420 subunits with a new fold. The final capsid maturation step is an autocatalytic reaction that creates 420 isopeptide bonds between proteins. Each subunit is joined to two of its neighbors by ligation of the side-chain lysine 169 to asparagine 356. This generates 12 pentameric and 60 hexameric rings of covalently joined subunits that loop through each other, creating protein chainmail: topologically linked protein catenanes arranged with icosahedral symmetry. Catenanes have not been previously observed in proteins and provide a stabilization mechanism for the very thin HK97 capsid. 相似文献
12.
Syntaxin, synaptosome-associated protein of 25 kD (SNAP25), and vesicle-associated membrane protein/synaptobrevin are collectively called SNAP receptor (SNARE) proteins, and they catalyze neuronal exocytosis by forming a "core complex." The steps in core complex formation are unknown. Here, we monitored SNARE complex formation in vivo with the use of a fluorescent version of SNAP25. In PC12 cells, we found evidence for a syntaxin-SNAP25 complex that formed with high affinity, required only the amino-terminal SNARE motif of SNAP25, tolerated a mutation that blocks formation of other syntaxin-SNAP25 complexes, and assembled reversibly when Ca2+ entered cells during depolarization. The complex may represent a precursor to the core complex formed during a Ca2+-dependent priming step of exocytosis. 相似文献
13.
Jiang L Althoff EA Clemente FR Doyle L Röthlisberger D Zanghellini A Gallaher JL Betker JL Tanaka F Barbas CF Hilvert D Houk KN Stoddard BL Baker D 《Science (New York, N.Y.)》2008,319(5868):1387-1391
The creation of enzymes capable of catalyzing any desired chemical reaction is a grand challenge for computational protein design. Using new algorithms that rely on hashing techniques to construct active sites for multistep reactions, we designed retro-aldolases that use four different catalytic motifs to catalyze the breaking of a carbon-carbon bond in a nonnatural substrate. Of the 72 designs that were experimentally characterized, 32, spanning a range of protein folds, had detectable retro-aldolase activity. Designs that used an explicit water molecule to mediate proton shuffling were significantly more successful, with rate accelerations of up to four orders of magnitude and multiple turnovers, than those involving charged side-chain networks. The atomic accuracy of the design process was confirmed by the x-ray crystal structure of active designs embedded in two protein scaffolds, both of which were nearly superimposable on the design model. 相似文献
14.
复杂腐蚀环境下HT-PO管道修复技术的应用 总被引：1，自引：0，他引：1
为了解决塔河油田集输管道在高H2S、CO2服役环境下短期内即产生腐蚀穿孔的问题,采用耐腐蚀管材耐热聚乙烯（HT—PO）管对现役管道实施内衬穿插修复。介绍了内衬管外径、壁厚及承压能力、流通能力的设计依据和计算方法,对内衬穿插工艺和施工工艺过程进行了阐述。该技术可以应用于因建筑物或水域等敷设受限条件下的管道修复,避免全线开挖更换,不但修复成本低,施工周期短,而且修复后的管道在复杂腐蚀环境下的适用性更强,可为类似油田集输管道防腐修复提供参考。（表1,参6） 相似文献
15.
根据血清1型鸭甲型肝炎病毒(DHAV-1)SH株3D基因序列设计并合成1对特异性引物,通过RT-PCR方法扩增3D基因,将其克隆入原核表达载体p ET-32a,转化大肠杆菌BL21(DE3),在IPTG的诱导培养下重组蛋白获得了成功表达。SDS-PAGE显示重组蛋白的分子量约为68 k D,Western blot分析显示该重组蛋白能与多聚组氨酸标签单抗发生特异性反应。将切胶后纯化的目的蛋白免疫ICR小鼠,制备针对重组蛋白的多抗血清,Western blot结果显示制备的抗血清能够与DHAV-1感染的SPF鸡胚尿囊液总蛋白发生特异反应。以上结果表明,3D基因在大肠杆菌中获得了成功表达,且制备的多抗血清可以用于3D蛋白的检测,为3D蛋白的功能研究奠定了基础。 相似文献
16.
Yin H Slusky JS Berger BW Walters RS Vilaire G Litvinov RI Lear JD Caputo GA Bennett JS DeGrado WF 《Science (New York, N.Y.)》2007,315(5820):1817-1822
A variety of methods exist for the design or selection of antibodies and other proteins that recognize the water-soluble regions of proteins; however, companion methods for targeting transmembrane (TM) regions are not available. Here, we describe a method for the computational design of peptides that target TM helices in a sequence-specific manner. To illustrate the method, peptides were designed that specifically recognize the TM helices of two closely related integrins (alphaIIbbeta3 and alphavbeta3) in micelles, bacterial membranes, and mammalian cells. These data show that sequence-specific recognition of helices in TM proteins can be achieved through optimization of the geometric complementarity of the target-host complex. 相似文献
17.
以OpenGL为工具,在VisualC++程序设计语言为平台上建立一个三维虚拟林相模型。通过坐标系设定、DEM加载、地形纹理设置、树木模型建立、天空建立等过程,说明虚拟林相建立的理论、方法和过程。最终实现了三维虚拟林相的显示、放大缩小和漫游功能。实践证明,所述的原理和方法能所实现的显示效果与ERDAS虚拟现实模块的效果基本相同,可以为林业规划显示系统的开发提供模块和技术支持。 相似文献
18.
Chworos A Severcan I Koyfman AY Weinkam P Oroudjev E Hansma HG Jaeger L 《Science (New York, N.Y.)》2004,306(5704):2068-2072
One challenge in supramolecular chemistry is the design of versatile, self-assembling building blocks to attain total control of arrangement of matter at a molecular level. We have achieved reliable prediction and design of the three-dimensional structure of artificial RNA building blocks to generate molecular jigsaw puzzle units called tectosquares. They can be programmed with control over their geometry, topology, directionality, and addressability to algorithmically self-assemble into a variety of complex nanoscopic fabrics with predefined periodic and aperiodic patterns and finite dimensions. This work emphasizes the modular and hierarchical characteristics of RNA by showing that small RNA structural motifs can code the precise topology of large molecular architectures. It demonstrates that fully addressable materials based on RNA can be synthesized and provides insights into self-assembly processes involving large populations of RNA molecules. 相似文献
19.
Type III secretion systems (T3SSs) are essential virulence factors used by many Gram-negative bacteria to inject proteins that make eukaryotic host cells accessible to invasion. The T3SS core structure, the needle complex (NC), is a ~3.5 megadalton-sized, oligomeric, membrane-embedded complex. Analyzing cryo-electron microscopy images of top views of NCs or NC substructures from Salmonella typhimurium revealed a 24-fold symmetry for the inner rings and a 15-fold symmetry for the outer rings, giving an overall C3 symmetry. Local refinement and averaging showed the organization of the central core and allowed us to reconstruct a subnanometer composite structure of the NC, which together with confident docking of atomic structures reveal insights into its overall organization and structural requirements during assembly. 相似文献
20.
Schnaufer A Panigrahi AK Panicucci B Igo RP Wirtz E Salavati R Stuart K 《Science (New York, N.Y.)》2001,291(5511):2159-2162
RNA editing in trypanosomes occurs by a series of enzymatic steps that are catalyzed by a macromolecular complex. The TbMP52 protein is shown to be a component of this complex, to have RNA ligase activity, and to be one of two adenylatable proteins in the complex. Regulated repression of TbMP52 blocks editing, which shows that it is a functional component of the editing complex. This repression is lethal in bloodforms of the parasite, indicating that editing is essential in the mammalian stage of the life cycle. The editing complex, which is present in all kinetoplastid parasites, may thus be a chemotherapeutic target. 相似文献