Three parallel algorithms for classical molecular dynamics are presented. The first assigns each processor a fixed subset of atoms; the second assigns each a fixed subset of inter-atomic forces to compute; the third assigns each a fixed spatial region. The algorithms are suitable for molecular dynamics models which can be difficult to parallelize efficiently—those with short-range forces where the neighbors of each atom change rapidly. They can be implemented on any distributed-memory parallel machine which allows for message-passing of data between independently executing processors. The algorithms are tested on a standard Lennard-Jones benchmark problem for system sizes ranging from 500 to 100,000,000 atoms on several parallel supercomputers--the nCUBE 2, Intel iPSC/860 and Paragon, and Cray T3D. Comparing the results to the fastest reported vectorized Cray Y-MP and C90 algorithm shows that the current generation of parallel machines is competitive with conventional vector supercomputers even for small problems. For large problems, the spatial algorithm achieves parallel efficiencies of 90% and a 1840-node Intel Paragon performs up to 165 faster than a single Cray C9O processor. Trade-offs between the three algorithms and guidelines for adapting them to more complex molecular dynamics simulations are also discussed.

Fast parallel algorithms for short-range molecular dynamics

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

Spurred by recent progress in materials chemistry and drug delivery, stimuli-responsive devices that deliver a drug in spatial-, temporal- and dosage-controlled fashions have become possible. Implementation of such devices requires the use of biocompatible materials that are susceptible to a specific physical incitement or that, in response to a specific stimulus, undergo a protonation, a hydrolytic cleavage or a (supra)molecular conformational change. In this Review, we discuss recent advances in the design of nanoscale stimuli-responsive systems that are able to control drug biodistribution in response to specific stimuli, either exogenous (variations in temperature, magnetic field, ultrasound intensity, light or electric pulses) or endogenous (changes in pH, enzyme concentration or redox gradients).

Stimuli-responsive nanocarriers for drug delivery

The Huisgen 1,3-dipolar cycloaddition reaction of organic azides and alkynes has gained considerable attention in recent years due to the introduction in 2001 of Cu(1) catalysis by Tornoe and Meldal, leading to a major improvement in both rate and regioselectivity of the reaction, as realized independently by the Meldal and the Sharpless laboratories. The great success of the Cu(1) catalyzed reaction is rooted in the fact that it is a virtually quantitative, very robust, insensitive, general, and orthogonal ligation reaction, suitable for even biomolecular ligation and in vivo tagging or as a polymerization reaction for synthesis of long linear polymers. The triazole formed is essentially chemically inert to reactive conditions, e.g. oxidation, reduction, and hydrolysis, and has an intermediate polarity with a dipolar moment of ∼5 D. The basis for the unique properties and rate enhancement for triazole formation under Cu(1) catalysis should be found in the high ∆G of the reaction in combination with the low character of polarity of the dipole of the noncatalyzed thermal reaction, which leads to a considerable activation barrier. In order to understand the reaction in detail, it therefore seems important to spend a moment to consider the structural and mechanistic aspects of the catalysis. The reaction is quite insensitive to reaction conditions as long as Cu(1) is present and may be performed in an aqueous or organic environment both in solution and on solid support.

Cu-catalyzed azide-alkyne cycloaddition.

The organization of inorganic nanostructures within self-assembled organic or biological templates is receiving the attention of scientists interested in developing functional hybrid materials. Previous efforts have concentrated on using such scaffolds to spatially arrange nanoscopic elements as a strategy for tailoring the electrical, magnetic or photonic properties of the material. Recent theoretical arguments have suggested that synergistic interactions between self-organizing particles and a self-assembling matrix material can lead to hierarchically ordered structures. Here we show that mixtures of diblock copolymers and either cadmium selenide- or ferritin-based nanoparticles exhibit cooperative, coupled self-assembly on the nanoscale. In thin films, the copolymers assemble into cylindrical domains, which dictate the spatial distribution of the nanoparticles; segregation of the particles to the interfaces mediates interfacial interactions and orients the copolymer domains normal to the surface, even when one of the blocks is strongly attracted to the substrate. Organization of both the polymeric and particulate entities is thus achieved without the use of external fields, opening a simple and general route for fabrication of nanostructured materials with hierarchical order.

Self-directed self-assembly of nanoparticle/copolymer mixtures

Fluorogenic Cu(I)-catalyzed alkyne–azide cycloaddition (CuAAC) reactions have emerged as a powerful tool for bioconjugation, materials science, organic synthesis and drug discovery. This review highlights the design of the recent development of fluorogenic CuAAC reactions as well as their applications.

Fluorogenic click reaction

Modern proteomic methods enable efficient identification of the hundreds or thousands of proteins present in whole cells or in isolated organelles. However, a thorough understanding of the proteome requires insight into protein localization as well as protein identity. Recently, visualization of newly synthesized proteins in bacterial cells was demonstrated through co-translational introduction of an alkynyl amino acid followed by selective CuI-catalyzed ligation of the alkynyl side chain to the fluorogenic dye 3-azido-7-hydroxycoumarin. Here we report that selective fluorescence labeling and imaging of newly synthesized proteins can be accomplished in a diverse set of mammalian cells.

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Fluorescence visualization of newly synthesized proteins in mammalian cells.

Self‐Assembly and Cross‐Linking of Bionanoparticles at Liquid–Liquid Interfaces

Cu-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) reaction, renascent of the well-known Huisgen reaction, has recently flourished with applications in organic synthesis, drug discovery, polymer and materials science, and biotechnology. The high reaction yield, simple reaction and purification conditions, wide range of solvent and pH stabilities, and functional group tolerance make the CuAAC reaction a prototypical “click chemistry”, ideal for incorporating functionalities onto desired scaffolds. Over the years it has been widely employed to construct and functionalize polymeric and polyvalent display systems, including polymers, dendrimers, nanoparticles, and surfaces, where an extremely high reaction efficiency for every unit reaction is desirable. In particular, as organic azides and alkynes are almost unreactive with biomolecules and water, CuAAC reactions have been employed in derivatizing biomacromolecules, viruses, and cells with high efficacy under mild reaction conditions. Recently tyrosine residues have been considered as a particularly attractive target for chemoselective modification of proteins because of its subabundant distribution. Francis and coworkers have reported a number of transformations, ranging from the Mannich-type reaction to a transition metal mediated allylation reaction to a diazonium-coupling reaction, which can efficiently target the phenolic group of tyrosine residues at physiological conditions. To overcome the sluggish reactivity with electron-enriched diazonium salts, a sequential reduction/oxidation/Diels–Alder reaction was developed to break the limitation of functionalities being incorporated. In this communication, we report that CuAAC reactions can be combined with a diazonium-coupling reaction to quantitatively functionalize tyrosine residues with a wide array of starting materials. Tobacco Mosaic Virus (TMV) is a classic example of rodlike plant viruses consisting of 2130 identical protein subunits arranged helically around genomic single RNA strand. The length of TMV, that is, 300 nm, is defined by the encapsulated genomic RNA that stabilizes the coat protein assembly. The polar outer and inner surfaces of TMV have been exploited as templates to grow metal or metal oxide nanowires, and conductive polymers have been coated on 1D assembled TMV to produce conductive nanowires. TMV based materials have recently shown great potential with applications in nanoelectronics and energy harvesting devices. In addition, it has been reported that tyrosine residues (Y139) of TMV are viable for chemical ligation using the electrophilic substitution reaction at the ortho position of the phenol ring with diazonium salts. This reaction is very efficient, yet has two distinct disadvantages for broader applications. First, it is difficult to synthesize desired starting materials; and second, the reaction is not compatible with acid-labile functional groups and suitable for electron-deficient anilines only. To embrace the structural diversity of various starting materials, TMV offers an ideal polyvalent display system which allows us to test the efficiency of CuAAC reaction in combining with the tyrosine ligation reaction. As shown in Scheme 1, TMV was first treated with the diazonium salt generated from 3-ethynylaniline 1 in situ adapted from the protocol reported by Francis and co-workers. MALDI-TOF MS analysis indicated that >95% of the capsid monomers were converted into alkyne derivatives 2 (Figure 1) despite the absence of a strong electron withdrawing group in the diazonium reagent. Encouraged by this result, the CuAAC reactions between 2 and azides were explored. For bioconjugation reactions using CuAAC, the Cu catalysts are either generated directly by addition of Cu salts, or in situ from soluble Cu sources and a reducing agent, such as a copper wire, phosphines, thiols, or ascorbate. Multidentate heterocyclic ligands are often required for enhancing the reaction efficiency. Upon screening a series of reaction conditions, we found that the combination of CuSO4/sodium ascorbate (NaAsc) gave the best results. Whereas it is destructive to most other protein complex systems, ascorbate is evidently benign to TMV and has no impact on its structural integrity. 3-Azido-7-hydroxy-coumarin a was first employed as the ACHTUNGTRENNUNGazido counterpart in the reaction, which could be easily monitored by UV-visible absorption at 340 nm (Figure 1B). As a general protocol, 2 (2 mgmL ) and a (3 mm) were added to a solution of CuSO4 (1 mm) and NaAsc (2 mm) in Tris buffer (10 mm, pH 7.8) with 20% DMSO (used to increase the solubility of the azide component). After incubation for 18 h at room temperature, the viral particles were separated from the small molecules by sucrose gradient sedimentation. The integrity of TMV was confirmed by TEM and size-exclusion chromatography (SEC) analysis (data not shown). A strong absorption at 340 nm indicated the successful attachment of coumarin motifs (Figure 1B). MALDI-TOF MS analysis indicated a near quantitative transformation of surface alkynes to triazoles as shown in Figure 1A. [a] M. A. Bruckman, G. Kaur, L. A. Lee, F. Xie, J. Sepulveda, Dr. Q. Wang Department of Chemistry and Biochemistry and Nanocenter University of South Carolina 631 Sumter Street, Columbia, South Carolina 29208 (USA) Fax: (+1)803-777-9521 E-mail : wang@mail.chem.sc.edu [b] R. Breitenkamp, X. Zhang, M. Joralemon, Dr. T. P. Russell, Dr. T. Emrick Polymer Science and Engineering Department, University of Massachusetts Conte Center for Polymer Research, Massachusetts 01003 (USA)

Qian Wang

Papers

Self-directed self-assembly of nanoparticle/copolymer mixtures

Fluorogenic click reaction

Fluorescence visualization of newly synthesized proteins in mammalian cells.

Self‐Assembly and Cross‐Linking of Bionanoparticles at Liquid–Liquid Interfaces

Surface Modification of Tobacco Mosaic Virus with “Click” Chemistry