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

1Introduction 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 alternating alpha-aminoacids with branching diaminoacids[1].Dendrimers containing combinations of histidine, serine and aspartate display enzyme-like catalytic properties for the hydrolysis of esters, including enantiomeric discrimination[1d]. The catalytic effect involves cooperative substrate binding and catalysis by a positive dendritic effect[1d].     

Alternating deposition films of a polymer and dendrimers bearing diphenylanthracene

Two generations of earboxyl-terminated poly (aryl ether) dendrimers bearing 9,10-diphenylanthracene cores are designed and synthesized. Alternating deposition of two dendrimers and poly(4-vinylpyridine) is studied with UV-Vis spectroscopy, FT-IR spectroscopy and atomic force microscopy. Experimental results indicate that this method to introduce chromophore into multilayer film can effectively prevent desorption of dye molecule. Moreover, it is found that dendrimer can inhibit the aggregation of fluorophore in film using fluorescence spectroscopy. Increase of dendrimer‘s generation can enhance fluorescence intensity of each fluorophore. This provides a new approach to design luminescent thin film.     

Product model structure for generalized optimal design

The framework of the generalized optimization product model with the core of network- and tree-hierarchical structure is advanced to improve the characteristics of the generalized optimal design. Based on the proposed node-repetition technique, a network-hierarchical structure is united with the tree-hierarchical structure to facilitate the modeling of serialization and combination products. The criteria for product decomposition are investigated. Seven tree nodes are defined for the construction of a general product model, and their modeling properties are studied in detail. The developed product modeling system is applied and examined successfully in the modeling practice of the generalized optimal design for a hydraulic excavator.     

Non-resonant structure design of catenary transformer in ultrasonic gear honing

To solve the design problem of transformer composed of non-resonant structure in ultrasonic gear-honing, force coupling conditions for moderately thick annular plate (MTAP) and catenary horn are proposed, and the frequency equations of the transformer, which consist of an MTAP and a catenary horn, are derived based on Mindlin’s theory. The design parameters of the transformer were obtained by solving the frequency equations with the help of MATLAB, and its mode and frequency were deduced by the modal analysis of finite element method (FEM), which are consistent with the theoretical design demands. The transformer design can be extended from system with thin annular plate to that with MTAP as the theoretical method by the simulation analysis of various ratios of the thickness to radius.     

Conformational change of glutathione-S-transferase by its co-expression with prion domain of yeast Ure2p

Ure2 protein from Saccharomyces cerevisisae has a changeable structure similar to that ofrnammalian prion protein. Its N-terminal is the prion domain (PrD) consisting of 65 amino acids which plays a critical role in yeast prion development. In this study, PrD gene was recombinated with glutathione-S-transferase(GST) gene, and a soluble GST-PrD(sGST-PrD) fusion protein was expressed in E. coli. sGST-PrD could spontaneously polymerize into amyloid fibrils in vitro, displaying typical β-sheet-type structure; it had increased resistance to proteinase K and exhibited amvloid-like optical properties. Moreover, the aggregated GST-PrD(aGST-PrD) could induce sGST-PrD to aggregate into fibrils. These results indicate that PrD could change the conformation of GST moiety in a recombinant protein with PrD to form a prion-like chimeric protein, which proves that PrD has the ability to mediate a prion-like conversion of other proteins fused with it.     

How the “Folding Funnel” Depends on Size and Structure of Proteins？A View from the Scoring Function Perspective

It has been well accepted that the folding energy landscape may resemble a funnel according to the theory of protein folding. This theory of "folding funnel" has been extensively studied and thought to play an important role in guiding the sampling process of the protein folding and refinement in protein structure prediction. Here, we have investigated the relationship between the "funnel likeness" of protein folding and the size/structure of the proteins based on a set of non-homologous proteins we have recently evaluated using a statistical mechanicsbased scoring function ITScorePro. It was found that larger proteins that consist of more helix/sheet structures tend to have a higher score-Root Mean Square Deviation(RMSD) correlation(or a more funnel like energy landscape).Another measurement in protein folding, Z-score, has also shown some correlation with the size of the proteins.As expected, proteins with a better "olding funnel likeness"(or score-RMSD correlation) tend to have a betterpredicted conformation with a lower RMSD from their native structures. These findings can be extremely valuable for the development and improvement of sampling and scoring algorithms for protein structure prediction.     

Dendritic Liquid Crystals:Self-organization and Nuclear Magnetic Relaxation Investigation of Their Molecular Dynamics

1 Results Liquid crystalline dendrimers and structurally related multipodes are supermolecules consisting of an amorphous hyper-branched core at the periphery of which are attached mesogenic groups capable of self-organization.Two opposite tendencies compete in these systems: the internal dendrimer tends to adopt a pseudo-spherical architecture that has a disordering influence on the packing of the mesogenic parts whose tend to self-organize into partially ordered structures.These kinds of systems show a rich variety of mesophases depending on the architecture of the hyper-branched part and the chemical structure of the mesogenic units.     

Interaction between poly（amidoamine） dendrimers and DNA studied by spectroscopic methods

The interaction between amino-terminated, and ethylenedtamine core poly（amtdoamine） （PAMAM） dendrimers and herring sperm DNA was investigated by various spectroscopic methods including UV spectroscopy, fluorescence spectroscopy, microscopic FTIR- and circular dichroism （CD-） spectroscopy. Ethidium bromide （EB） is used as a nucleic acid probe for this study. Experimental results show that PAMAM dendrimers can form stable complexes with DNA and the dendrimers bind to DNA sufficiently strong which cannot be displaced by EB, and we also found that the formation of the complexes can cause the conformation change of the DNA secondary structure. According to the Scatchard analysis, the association constant of PAMAM to DNA is calculated to be 2.53×10^4 mol/L^-1.     

A case study of 3D protein structure prediction with genetic algorithm and Tabu search

This paper describes a case study of 3D protein structure prediction of six sequences from protein data bank (PDB) by genetic algorithm and tabu search (GATS), where off-lattice AB model is considered as a simplified model of protein structure. The lowest-energy values required for forming the native conformation of proteins are searched by GATS, and then the coarse structures (i.e., simplified structure) of the proteins are obtained according to the multiple angle parameters corresponding to the lowest energies. All the coarse structures form single hydrophobic cores surrounded by hydrophilic residues, which stay on the right side of the actual characteristic of protein structure. It demonstrates that this approach can predict the 3D protein structure effectively.     

Hierarchically Clustered HMM for Protein Sequence Motif Extraction with Variable Length

Protein sequence motifs extraction is an important field of bioinformatics since its relevance to the structural analysis. Two major problems are related to this field：（1） searching the motifs within the same protein family; and（2） assuming a window size for the motifs search. This work proposes the Hierarchically Clustered Hidden Markov Model（HC-HMM） approach, which represents the behavior and structure of proteins in terms of a Hidden Markov Model chain and hierarchically clusters each chain by minimizing distance between two given chains＇ structure and behavior. It is well known that HMM can be utilized for clustering, however, methods for clustering on Hidden Markov Models themselves are rarely studied. In this paper, we developed a hierarchical clustering based algorithm for HMMs to discover protein sequence motifs that transcend family boundaries with no assumption on the length of the motif. This paper carefully examines the effectiveness of this approach for motif extraction on 2593 proteins that share no more than 25% sequence identity. Many interesting motifs are generated.Three example motifs generated by the HC-HMM approach are analyzed and visualized with their tertiary structure.We believe the proposed method provides a unique protein sequence motif extraction strategy. The related data mining fields using Hidden Markova Model may also benefit from this clustering on HMM themselves approach.     

Four basic laws in design science

A point on the distinction between design and science is given and the connotanons of aeslgn science are discussed in the paper. Design should be understood as the first step of all human＇ s purposeful activity, which is a daily behavior for everyone. Four laws are summarized, which describe the basic patterns of design and are the constituents of design science. They are the law of design based on existed knowledge, law of in- completeness of design knowledge, law of design centered on new knowledge acquirement and law of competi- tiveness of design knowledge. The four basic laws show the knowledge essence of design. To enrich the existed knowledge, to make it convenient to be used, to teach designers with high intuition and inspiration in picking useful elements of existed knowledge and shaping competitive ideas and to have strong new knowledge acquire- ment facility are the basic conditions of good designs. Study of design science will promote the structure of tra- ditional engineering education. An important conclusion is derived that there will be no successful innovation without good design.     

TLP hull structural design and analysis

Tension leg platform (TLP) has been one of the most favorite deep-water platform concepts for offshore oil and gas field exploration and development. As of now,a total of 24 TLPs have been installed worldwide with 3 more to be installed in the near future and 5 more under design. Most of these installations are in the Gulf of Mexico (GoM). Water depths for these TLP installations range from 150 m to 1 600 m. It is highly expected that China will have her first TLP designed,fabricated,and installed in the very near future. In order to satisfy the need for a unified hull structural design practice,this paper presents the design philosophy of a conventional TLP hull structure with emphases on critical structural components design and analysis methodologies.     

Reliability Based Design Optimization of Aero-Engine Spindle Ball Bearings

Aero-engine spindle ball bearings work in harsh conditions which are affected by relatively complex stresses. One of the key factors which affects bearing performance is its structure. In this paper,we used reliability based design optimization method to solve the structure design problem of aero-engine spindle ball bearings.Compared with the optimization design method, the value of equivalent dynamic load using reliability optimization design method was the least by MATLAB simulation. Also the design solutions show that the optimized structure possesses higher reliability than the original solution.     

Optimization model of a structural simulation design for a CICC

The engineering design of a Cable-In-Conduit Conductor (CICC) is complicated. A model for the optimal design of a CICC based on conductor stability, AC loss and strain is proposed. The model considers the critical current density as a function of applied strain. A mathematical programming method that minimizes the AC loss of the CICC is established to yield an optimal design for the CICC structure. The optimized structure and related performance agree well with the engineering design values used for the KSTAR project.     

Effects of Different Types of Socks on Plantar Pressures,In-shoe Temperature and Humidity in Diabetic Patients

This study aims to evaluate the efficacy of different types of socks for patients with diabetes on reducing in-shoe plantar foot pressure when standing and walking. A total of 5 types of socks,including 3 types of diabetic socks and 2 types of daily /sports socks of various structures are studied. The effects of sock fabrication and design on plantar pressure redistribution that resulting in increasing the underfoot contact area and reducing the risk of pressure ulceration,as well as foot skin temperature and humidity, are examined. The results reveal that regardless of the different knitting structure,thickness and airspace ratio of the sock,both diabetic and daily /sports socks can effectively reduce high plantar pressure on the rear foot,and re-distribute the pressure to other foot regions,like the metatarsal heads. The effects of fabrication and knitting structure on pressure reduction and redistribution are not apparent in this study. However,they have a major impact on the control of foot skin temperature and humidity. The results of the study provide a reference for optimizing the design and functional performance of socks for patients with diabetes.     

Representation of 3D Woven Structures by Parametric Method

A parametric method is developed to quantitatively represent the microstructure of 3D woven structures. Different binding patterns, such as angle interlock and orthogonal interlock with through-thickness or layer-to-layer bindings, are classified. A unit cell of 3D woven structure is defined with four constituent yarn systems represented by nine structural parameters. A mapping relationship between the 3D woven structure and corresponding representative parameters is thus established. The study indicates that four out of the nine parameters are necessary to represent a 3D woven structure with an angle interlock binding, and that five parameters are required to describe a 3D woven structure with an orthogonal interlock binding. Once the structural parameters are determined, the pattern of 3D woven structures can be unambiguously identified, and vice versa. In addition to the purpose of structure presentation, the method can be further used as a means for designing 3D woven structure to meet the performance requirements of 3D woven composites.     

Tunable left-handed metamaterial based on electrorheological fluids

A tunable left-handed metamaterial consisting of a periodic array of the left-handed dendritic structure units infiltrated with electrorheological fluids is demonstrated. Experimental results show that the passband can move from the original 8.50-10.60 GHz to 7.16- 8.39 GHz after electrorheological fluids are infused. When a dc （direct current） electric field of 666 V/mm is applied, the passband moves toward lower frequency of within 7.08-8.30 GHz. This method provides one convenient way to design adaptive metamaterials.     

Mining Protein Complexes from PPI Networks Using the Minimum Vertex Cut

Evidence shows that biological systems are composed of separable functional modules. Identifying protein complexes is essential for understanding the principles of cellular functions. Many methods have been proposed to mine protein complexes from protein-protein interaction networks. However, the performances of these algorithms are not good enough since the protein-protein interactions detected from experiments are not complete and have noise. This paper presents an analysis of the topological properties of protein complexes to show that although proteins from the same complex are more highly connected than proteins from different complexes, many protein complexes are not very dense (density 0.8). A method is then given to mine protein complexes that are relatively dense (density 0.4). In the first step, a topology property is used to identify proteins that are probably in a same complex. Then, a possible boundary is calculated based on a minimum vertex cut for the protein complex. The final complex is formed by the proteins within the boundary. The method is validated on a yeast protein-protein interaction network. The results show that this method has better performance in terms of sensitivity and specificity compared with other methods. The functional consistency is also good.     

The principle of minimization of the equivalent load for design of launching vertical shiplift

Launching vertical shiplift is a type of shiplifts which have the advantages in characteristics of dynamics and statics, safety and simplicity in operation. But their applications are limited as the scales of mechanical equipments are too large. This paper puts forward the principle of minimization of the equivalent load for the general layout design of launching vertical shiplifts, based on the analysis of the load probability of the main hoists and their key mechanical equipments. The principle aims at determining the optimal weight of counterweight so that the equivalent loads of the main hoists of shiplifls are minimized, and larger ships are permitted to pass through. The theory and method presented in this paper have been applied in the design of the first step and third step shiplifts of the Goupitan Hydro Power Station. This has resulted in the breakthrough of the design and manufacture of launching vertical shiplifts so that the ships with tonnage of 500 t can pass through hydro dams for this type of shiplifts, comparing with the largest launching shiplift in Yantan Hydro Power Station with the 250 t shiplift.     

Structural Research on Embedment of a Bare Deflated Spiral Case

Complete bearing spiral case has not been applied to large power stations in China so far. The proposal of applying complete bearing spiral case necessitates an analysis of the reliability of the spiral case structure and the security of units under various working conditions. In combination with practice of a project, this paper presents a three-dimensional nonlinear finite element static analysis of the concrete using a concrete smeared crack model by means of the well-known finite element method （FEM） software ABAQUS. The stress distribution of the spiral case and reinforcing bars, the range of damages in surrounding concrete, and the displacement of structure are quantified. The computational results indicate that the embedment method ensures the structure＇s safety in strength. At the same time, the result shows that this embedment is a kind of preponderant method for embedment in aspects of economy and technique of construction, and the application of this embedment method to the hydropower station is feasible provided that some proper engineering measures are taken to constrain the width of the concrete in accord with the code＇s requirements. The paper proves the security and reliability of the structural design of spiral case in hydropower station accordingly.