Recent Progress in Fluorescence Signal Design for DNA-Based Logic Circuits

DNA-based logic circuits, encoding algorithms in DNA and processing information, are pushing the frontiers of molecular computers forward, owing to DNA′s advantages of stability, accessibility, manipulability, and especially inherent biological significance and potential medical application. In recent years, numerous logic functions, from arithmetic to nonarithmetic, have been realized based on DNA. However, DNA can barely provide a detectable signal by itself, so that the DNA-based circuits depend on extrinsic signal actuators. The signal strategy of carrying out a response is becoming one of the design focuses in DNA-based logic circuit construction. Although work on sequence and structure design for DNA-based circuits has been well reviewed, the strategy on signal production lacks comprehensive summary. In this review, we focused on the latest designs of fluorescent output for DNA-based logic circuits. Several basic strategies are summarized and a few designs for developing multi-output systems are provided. Finally, some current difficulties and possible opportunities were also discussed.     

DNA origami nanostructures for controlled therapeutic drug delivery

DNA nanostructures are emerging as a versatile platform for controlled drug delivery as a result of recent progress in production yield and strategies to obtain prolonged stability in biological environments. The construction of nanostructures from this unique biomaterial provides unparalleled control over structural and functional parameters. Recent applications of DNA origami-based nanocarriers for therapeutic drug delivery in preclinical phases highlight them as promising alternatives to conventional nanomaterials, as they benefit from the inherent favorable properties of DNA including biocompatibility and precise spatial addressability. By incorporating targeting aptamers and responsive properties into the nanocarrier design, more selective DNA origami-based nanocarriers are successfully prepared. On the other hand, current systems remain poorly understood in terms of biodistribution, final fate, and controlled drug release. As such, advances are needed to translate this material platform in its full potential for therapeutic applications.     

CANADA: Designing nucleic acid sequences for nanobiotechnology applications

The design of nucleic acid sequences for a highly specific and efficient hybridization is a crucial step in DNA computing and DNA‐based nanotechnology applications. The CANADA package contains software tools for designing DNA sequences that meet these and other requirements, as well as for analyzing and handling sequences. CANADA is freely available, including a detailed manual and example input files, at http://ls11‐www.cs.uni‐dortmund.de/molcomp/downloads . © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010     

Confinement effects on electromigration of long DNA molecules in an ordered cavity array

Confinement effects on the electromigration of long dsDNA molecules in an array of well-ordered, molecular sized cavities interconnected by nanopores are described. The array was prepared by replicating the structure of a colloidal crystal of microspheres in a polymer matrix. Both conformation and mobility studies show that the electrophoretic behavior of large DNA molecules is distinct from that in gels and other microfabricated sieves, showing a peak in mobility versus electric field, and an inversion in the separation order with field strength. A simple model was proposed to interpret this unexpected observation qualitatively. We conclude that the molecular behavior of DNA can be modified by the combination of entropic effect and electric trapping as a consequence of both unique geometry and conductivity of this cavity array material. This approach provides insights for design and optimization of on-chip molecular sieving structures for rapid separation of long DNA molecules. It may lead to a promising material for manipulation and size fractionation of other biological macromolecules.     

Quantum computing measurement and intelligence

One of the grand challenges in the nanoscopic computing era is guarantees of robustness. Robust computing system design is confronted with quantum physical, probabilistic, and even biological phenomena, and guaranteeing high‐reliability is much more difficult than ever before. Scaling devices down to the level of single electron operation will bring forth new challenges due to probabilistic effects and uncertainty in guaranteeing “zero‐one” based computing. Minuscule devices imply billions of devices on a single chip, which may help mitigate the challenge of uncertainty by replication and redundancy. However, such device densities will create a design and validation nightmare with the sheer scale. The questions that confront computer engineers regarding the current status of nanocomputing material and the reliability of systems built from such minuscule devices are difficult to articulate and answer. This article illustrates and discusses two types of quantum algorithms as follows: (1) a simple quantum algorithm and (2) a quantum search algorithm. This article also presents a review of recent advances in quantum computing and intelligence and presents major achievements and obstacles for researchers in the near future. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010     

Simulation of DNA electrophoresis in systems of large number of solvent particles by coarse-grained hybrid molecular dynamics approach

Simulation of DNA electrophoresis facilitates the design of DNA separation devices. Various methods have been explored for simulating DNA electrophoresis and other processes using implicit and explicit solvent models. Explicit solvent models are highly desired but their applications may be limited by high computing cost in simulating large number of solvent particles. In this work, a coarse-grained hybrid molecular dynamics (CGH-MD) approach was introduced for simulating DNA electrophoresis in explicit solvent of large number of solvent particles. CGH-MD was tested in the simulation of a polymer solution and computation of nonuniform charge distribution in a cylindrical nanotube, which shows good agreement with observations and those of more rigorous computational methods at a significantly lower computing cost than other explicit-solvent methods. CGH-MD was further applied to the simulation of DNA electrophoresis in a polymer solution and in a well-studied nanofluidic device. Simulation results are consistent with observations and reported simulation results, suggesting that CGH-MD is potentially useful for studying electrophoresis of macromolecules and assemblies in nanofluidic, microfluidic, and microstructure array systems that involve extremely large number of solvent particles, nonuniformly distributed electrostatic interactions, bound and sequestered water molecules.     

Self-assembled free-floating nanomaterials from sequence-defined polymers

Sequence-defined polymers can be programmed to self-assemble into precise nanostructures for applications in biosensing, drug delivery, optics, and molecular computation. Inspired by the natural self-assembly processes present in biological protein and DNA systems, sets of molecular design rules have emerged across materials classes as instructions to build a variety of tunable structures. This review highlights recent advances in self-assembled sequence-defined and sequence-specific polymers across peptides, peptoids, DNA, and non-biological synthetic materials, with a focus on synthesis, assembly processes and overall structure. Specifically, these self-assembled structures are free-floating, as such constructs can potentially serve as a platform for the aforementioned applications. Emphasis is placed on the molecular design of polymers that self-assemble into zero-dimensional, one-dimensional, two-dimensional, or three-dimensional nanostructures. With the development of automated syntheses and increasing control over self-assembly, future work may focus on emerging classes of compatible hybrid materials with exciting directions toward new architectures and applications.     

CUDA ClustalW: An efficient parallel algorithm for progressive multiple sequence alignment on Multi-GPUs

For biological applications, sequence alignment is an important strategy to analyze DNA and protein sequences. Multiple sequence alignment is an essential methodology to study biological data, such as homology modeling, phylogenetic reconstruction and etc. However, multiple sequence alignment is a NP-hard problem. In the past decades, progressive approach has been proposed to successfully align multiple sequences by adopting iterative pairwise alignments. Due to rapid growth of the next generation sequencing technologies, a large number of sequences can be produced in a short period of time. When the problem instance is large, progressive alignment will be time consuming. Parallel computing is a suitable solution for such applications, and GPU is one of the important architectures for contemporary parallel computing researches. Therefore, we proposed a GPU version of ClustalW v2.0.11, called CUDA ClustalW v1.0, in this work. From the experiment results, it can be seen that the CUDA ClustalW v1.0 can achieve more than 33× speedups for overall execution time by comparing to ClustalW v2.0.11.     

GridMol: a grid application for molecular modeling and visualization

In this paper we present GridMol, an extensible tool for building a high performance computational chemistry platform in the grid environment. GridMol provides computational chemists one-stop service for molecular modeling, scientific computing and molecular information visualization. GridMol is not only a visualization and modeling tool but also simplifies control of remote Grid software that can access high performance computing resources. GridMol has been successfully integrated into China National Grid, the most powerful Chinese Grid Computing platform. In Section “Grid computing” of this paper, a computing example is given to show the availability and efficiency of GridMol. GridMol is coded using Java and Java3D for portability and cross-platform compatibility (Windows, Linux, MacOS X and UNIX). GridMol can run not only as a stand-alone application, but also as an applet through web browsers. In this paper, we will present the techniques for molecular visualization, molecular modeling and grid computing. GridMol is available free of charge under the GNU Public License (GPL) from our website: Contact:      

Visual Displays that Directly Interface and Provide Read‐Outs of Molecular States via Molecular Graphics Processing Units

The monitoring of molecular systems usually requires sophisticated technologies to interpret nanoscale events into electronic‐decipherable signals. We demonstrate a new method for obtaining read‐outs of molecular states that uses graphics processing units made from molecular circuits. Because they are made from molecules, the units are able to directly interact with molecular systems. We developed deoxyribozyme‐based graphics processing units able to monitor nucleic acids and output alphanumerical read‐outs via a fluorescent display. Using this design we created a molecular 7‐segment display, a molecular calculator able to add and multiply small numbers, and a molecular automaton able to diagnose Ebola and Marburg virus sequences. These molecular graphics processing units provide insight for the construction of autonomous biosensing devices, and are essential components for the development of molecular computing platforms devoid of electronics.     

Open computing grid for molecular science and engineering

Grid is an emerging infrastructure for distributed computing that provides secure and scalable mechanisms for discovering and accessing remote software and data resources. Applications built on this infrastructure have great potential for addressing and solving large scale chemical, pharmaceutical, and material science problems. The article describes the concept behind grid computing and will present the OpenMolGRID system that is an open computing grid for molecular science and engineering. This system provides grid enabled components, such as a data warehouse for chemical data, software for building QSPR/QSAR models, and molecular engineering tools for generating compounds with predefined chemical properties or biological activities. The article also provides an overview about the availability of chemical applications in the grid.     

DNA Nanotechnology-based Biocomputing

With silicon-based microelectronic technology pushed to its limit,scientists hunt to exploit biomolecules to power the bio-computer as substitutes.As a typical biomolecule,DNA now has been employed as a tool to create computing systems because of its superior parallel computing ability and outstanding data storage capability.However,the key challenges in this area lie in the human intervention during the computation process and the lack of platforms for central processor.DNA nanotechnology has created hundreds of complex and hierarchical DNA nanostructures with highly controllable motions by exploiting the unparalleled self-recognition properties of DNA molecule.These DNA nanostructures can provide platforms for central processor and reduce the human intervention during the computation process,which can offer unprecedented opportunities for biocomputing.In this review,recent advances in DNA nanotechnology are briefly summarized and the newly emerging concept of biocomputing with DNA nanostructures is introduced.     

Connectable DNA Logic Gates: OR and XOR Logics

Modern computer processors are based on semiconductor logic gates connected to each other in complex circuits. This study contributes to the development of a new class of connectable logic gates made of DNA in which the transfer of oligonucleotide fragments as input/output signals occurs upon hybridization of DNA sequences. The DNA strands responsible for a logic function form associates containing immobile DNA four‐way junction structures when the signal is high and dissociate into separate strands when the signal is low. A basic set of logic gates (NOT, AND, and OR) was designed. Two NOT gates, two AND gates, and an OR gate were connected in a network that corresponds to an XOR logic function. The design of the logic gates presented here may contribute to the development of the first biocompatible molecular computer.     

Recent progress on DNA block copolymer

Organic polymers are combined with DNA resulting DNA block copolymers (DBCs) that can simultaneously show the properties of the polymer and DNA. We will discuss some examples of recent developments in the syntheses, structure manipulations, and applications of DBCs.     

A Supramolecular Counter Circuit Based on Cyanine Dye Assembly

Molecular computation, a rapidly developing multidisciplinary research field, has attracted increasing attention. A series of combinational logic circuits at the molecular level have been constructed, however, the development of sequential logic circuits is still in its infancy due to the lack of ideal design tools. Taking advantage of unique assembly behaviors of cyanine dyes, we constructed a two-bit molecular counter circuit that can implement fundamental sequential logic functions, including number cumulating and descending. Further introducing a guanine-rich DNA strand as the cycle index, the counter can be reused several times and eventually be scaled up to count up to 16 numbers. The supramolecular circuit shows high programmability, flexibility, and reversibility, and it is prospected that the strategy would be applied in designing other advanced molecular circuits.     

大学化学云计算学习环境与协作学习模型的构建

"云计算"在教育教学中的应用构建了"云计算"辅助教学的概念。21世纪的教学方式是以学为主、以教为辅,学习的方式也从个人学习变成了协作学习,这正是"云计算"辅助教学的核心。本文回顾了计算机辅助教学的发展,对"云计算"学习环境与协作学习模型的构建进行了分析探讨,并以"大学化学云学堂"为案例解析了"云计算"学习环境与协作学习模型建立的实际应用,阐述了其设计思路和实现方法,以期为"云计算"辅助学习与教学研究提供一些帮助。     

Exploring chemistry with the fragment molecular orbital method

The fragment molecular orbital (FMO) method makes possible nearly linear scaling calculations of large molecular systems, such as water clusters, proteins and DNA. In particular, FMO has been widely used in biochemical applications involving protein-ligand binding and drug design. The method has been efficiently parallelized suitable for petascale computing. Many commonly used wave functions and solvent models have been interfaced with FMO. We review the historical background of FMO, and summarize its method development and applications.     

DNA纳米机器:梦想照进现实

可进体内治病救人的纳米机器人一直是人们梦寐以求的未来科技和医疗手段.最近,国家纳米科学中心的丁宝全、聂广军等在这个方向取得了重要的突破,成功开发了基于DNA纳米机器的癌症免疫治疗疫苗.他们首先利用DNA折纸术构筑了一个可精确负载抗原和佐剂的管状结构,通过皮下注射递送至淋巴结,经由内吞在树突细胞内涵体内发生pH响应性的锁链打开,暴露抗原和佐剂,从而激活树突细胞,产生抗原特异性的T细胞,有效杀伤肿瘤细胞.该疫苗不仅可以有效抑制肿瘤的生长和复发,还诱导特异性记忆效应,可持续产生特异性的保护.这提供了一个精准递送分子药物的平台,让人看到成功发展纳米机器人的曙光,有望给医学和医疗保健带来重要变革.     

DNA Nanostructures as Drug Carriers for Cellular Delivery

Drug delivery systems have been widely developed for enhancing target activity and improving drug functions.Liposomes,high-molecular polymer,gold nanoparticles and carbon nanomaterials,etc.,are all the candidates of drug carriers.However,immunotoxicity,heterogeneity and low solubility generally exist and hamper their applications.As a kind of biological materials,DNA has its unique advantages in biomedical applications,including excellent biological compatibility and programmability.DNA nanostructures have been proved to possess high cellular uptake efficiency,which sheds new light on DNA-based drug delivery system.In this review,we summarize the influence factors of DNA nanostructure internalization efficiency,including cell lines,and the size and the shape of DNA nanoparticles.Uniformity of DNA nanostructures in appearance and properties ensures the stability in research,which makes DNA carriers stand out from other nanomaterials.Next,we focus on the functionalization of DNA carriers,which endows DNA nanostructures with the potential to construct integrated drug delivery platforms.We also discuss the internalization pathways of DNA nanostructures and their fate in cells.The deeply understanding about the endocytic pathways provides new sight for the further design strategy on changing the transportation routes of DNA carriers in cells.Finally,the challenges in further applications are discussed,and suggestions are proposed.