http://www.jsystchem.com The most accessed research articles published by Journal of Systems Chemistry 2012-02-03T00:00:00Z Though Darwinian theory dramatically revolutionized biological understanding, its strictly biological focus has resulted in a widening conceptual gulf between the biological and physical sciences. In this paper we strive to extend and reformulate Darwinian theory in physicochemical terms so it can accommodate both animate and inanimate systems, thereby helping to bridge this scientific divide. The extended formulation is based on the recently proposed concept of dynamic kinetic stability and data from the newly emerging area of systems chemistry. The analysis leads us to conclude that abiogenesis and evolution, rather than manifesting two discrete stages in the emergence of complex life, actually constitute one single physicochemical process. Based on that proposed unification, the extended theory offers some additional insights into life's unique characteristics, as well as added means for addressing the three central questions of biology: what is life, how did it emerge, and how would one make it? http://www.jsystchem.com/content/2/1/1 Addy Pross Journal of Systems Chemistry 2011, null:1 2011-06-07T00:00:00Z doi:10.1186/1759-2208-2-1 /content/figures/1759-2208-2-1-toc.gif Journal of Systems Chemistry 1759-2208 ${item.volume} 1 2011-06-07T00:00:00Z XML It is our utmost pleasure to launch the Journal of Systems Chemistry. What systems chemistry exactly is will be known in a few years from now when one is able to sketch the scope and vision of the field also based on upcoming contributions to our journal. How systems chemistry came up is more easy to tell. In this editorial we therefore focus predominantly on how the term "Systems Chemistry" came into being and how its scope evolved over recent years. It is perhaps not surprising that the term emerged within the communities researching the origin and synthesis of life, as this is probably the most challenging question in Systems Chemistry. The field however encompasses much more than just this subject - it offers a plethora of new opportunities for the discovery of life-like dynamic signatures in all areas in chemistry. http://www.jsystchem.com/content/1/1/1 Gunter von Kiedrowski Sijbren Otto Piet Herdewijn Journal of Systems Chemistry 2010, null:1 2010-08-18T00:00:00Z doi:10.1186/1759-2208-1-1 /content/figures/1759-2208-1-1-toc.gif Journal of Systems Chemistry 1759-2208 ${item.volume} 1 2010-08-18T00:00:00Z XML The first RNA World models were based on the concept of an RNA replicase - a ribozyme that was a good enough RNA polymerase that it could catalyze its own replication. Although several RNA polymerase ribozymes have been evolved in vitro, the creation of a true replicase remains a great experimental challenge. At first glance the alternative, in which RNA replication is driven purely by chemical and physical processes, seems even more challenging, given that so many unsolved problems appear to stand in the way of repeated cycles of non-enzymatic RNA replication. Nevertheless the idea of non-enzymatic RNA replication is attractive, because it implies that the first heritable functional RNA need not have improved replication, but could have been a metabolic ribozyme or structural RNA that conferred any function that enhanced protocell reproduction or survival. In this review, I discuss recent findings that suggest that chemically driven RNA replication may not be completely impossible. http://www.jsystchem.com/content/3/1/2 Jack Szostak Journal of Systems Chemistry 2012, null:2 2012-02-03T00:00:00Z doi:10.1186/1759-2208-3-2 The path to non-enzymatic RNA replication The original RNA World model is based on the concept of an RNA replicase. However, non-enzymatic RNA replication overcomes some of the problems with this model, and recent findings suggesting that this may have been possible are discussed in this Perspective /content/figures/1759-2208-3-2-toc.gif Journal of Systems Chemistry 1759-2208 ${item.volume} 2 2012-02-03T00:00:00Z XML Autocatalytic cycles are rather common in biological systems and they might have played a major role in the transition from non-living to living systems. Several theoretical models have been proposed to address the experimentalists during the investigation of this issue and most of them describe a phase transition depending upon the level of heterogeneity of the chemical soup. Nevertheless, it is well known that reproducing the emergence of autocatalytic sets in wet laboratories is a hard task. Understanding the rationale at the basis of such a mismatch between theoretical predictions and experimental observations is therefore of fundamental importance.We here introduce a novel stochastic model of catalytic reaction networks, in order to investigate the emergence of autocatalytic cycles, sensibly considering the importance of noise, of small-number effects and the possible growth of the number of different elements in the system.Furthermore, the introduction of a temporal threshold that defines how long a specific reaction is kept in the reaction graph allows to univocally define cycles also within an asynchronous framework.The foremost analyses have been focused on the study of the variation of the composition of the incoming flux. It was possible to show that the activity of the system is enhanced, with particular regard to the emergence of autocatalytic sets, if a larger number of different elements is present in the incoming flux, while the specific length of the species seems to entail minor effects on the overall dynamics. http://www.jsystchem.com/content/2/1/2 Alessandro Filisetti Alex Graudenzi Roberto Serra Marco Villani Davide De Lucrezia Rudolf Fuchslin Stuart Kauffman Norman Packard Irene Poli Journal of Systems Chemistry 2011, null:2 2011-06-22T00:00:00Z doi:10.1186/1759-2208-2-2 /content/figures/1759-2208-2-2-toc.gif Journal of Systems Chemistry 1759-2208 ${item.volume} 2 2011-06-22T00:00:00Z XML Recent reports about enantioselective organoautocatalytic systems, in which small organic molecules assist in their own formation and under conservation of their absolute configuration, are discussed. This process, appearing as a natural extension to non-covalent enantioselective organocatalysis, seems analogous to template-directed self-replication, previously observed in simple organic molecules and holds implications for models on the origin of life. http://www.jsystchem.com/content/1/1/8 Svetlana Tsogoeva Journal of Systems Chemistry 2010, null:8 2010-08-18T00:00:00Z doi:10.1186/1759-2208-1-8 /content/figures/1759-2208-1-8-toc.gif Journal of Systems Chemistry 1759-2208 ${item.volume} 8 2010-08-18T00:00:00Z XML Background: One of the remaining questions in the understanding of the origin of Nature's information system is the way the first nucleic acids have been synthesized. This could have been realized using nucleoside triphosphates or imidazolides of nucleoside monophosphates as building blocks. Alternatively, dinucleoside pyrophosphates could have been used for this purpose. The advantage of using building blocks, composed of pyrophosphate-linked dinucleotides, could be that exponential growth of initial information (dinucleotides) without product inhibition might become possible. Results: Herein, we demonstrate that dinucleoside pyrophosphates are able to act as substrate for HIV-1 RT and several thermostable DNA polymerases. In single incorporation assay, compound dAppdA was able to give a 100% conversion to the (P+1) strand by Therminator DNA polymerase and at a substrate concentration above 100 μM. Full-length elongation was obtained in a chain elongation experiment, with over 95% yield of (P+7) product by Taq and Vent (exo-) DNA polymerase. Interestingly, using heterodimer dAppdT addition of either nucleotide component of the dinucleotide substrate into the DNA chain can occur, which is defined by the template program. Conclusions: This study shows that dinucleoside pyrophosphates can be considered as a new type of substrate for polymerases in the template-directed DNA synthesis. Using heterodimers as substrate, theoretically, it is possible to synthesize DNA enzymatically using two building blocks (dAppdT and dGppdC) instead of four. Given the poor Km value for the nucleotide incorporation, evolution of polymerases will become necessary to make this process of practical use. http://www.jsystchem.com/content/2/1/3 Xiao-Ping Song Mohitosh Maiti Piet Herdewijn Journal of Systems Chemistry 2011, null:3 2011-10-04T00:00:00Z doi:10.1186/1759-2208-2-3 /content/figures/1759-2208-2-3-toc.gif Journal of Systems Chemistry 1759-2208 ${item.volume} 3 2011-10-04T00:00:00Z XML Background: Molecular recognition at the environment provided by the phospholipid bilayer interface plays an important role in biology and is subject of intense investigation. Dynamic combinatorial chemistry is a powerful approach for exploring molecular recognition, but has thus far not been adapted for use in this special microenvironment. Results: Thioester exchange was found to be a suitable reversible reaction to achieve rapid equilibration of dynamic combinatorial libraries at the egg phosphatidyl choline bilayer interface. Competing thioester hydrolysis can be minimised by judicial choice of the structure of the thioesters and the experimental conditions. Comparison of the library compositions in bulk solution with those in the presence of egg PC revealed that the latter show a bias towards the formation of library members rich in membrane-bound building blocks. This leads to a shift away from macrocyclic towards linear library members. Conclusions: The methodology to perform dynamic combinatorial chemistry at the phospholipid bilayer interface has been developed. The spatial confinement of building blocks to the membrane interface can shift the ring-chain equilibrium in favour of chain-like compounds. These results imply that interfaces may be used as a platform to direct systems to the formation of (informational) polymers under conditions where small macrocycles would dominate in the absence of interfacial confinement. http://www.jsystchem.com/content/1/1/12 Friederike Mansfeld Ho Yu Au-Yeung Jeremy Sanders Sijbren Otto Journal of Systems Chemistry 2010, null:12 2010-09-08T00:00:00Z doi:10.1186/1759-2208-1-12 /content/figures/1759-2208-1-12-toc.gif Journal of Systems Chemistry 1759-2208 ${item.volume} 12 2010-09-08T00:00:00Z XML While studying fatty acid vesicles as model primitive cell membranes, we encountered a dramatic phenomenon in which light triggers the sudden rupture of micron-scale dye-containing vesicles, resulting in rapid release of vesicle contents. We show that such vesicle explosions are caused by an increase in internal osmotic pressure mediated by the oxidation of the internal buffer by reactive oxygen species (ROS). The ability to release vesicle contents in a rapid, spatio-temporally controlled manner suggests many potential applications, such as the targeted delivery of cancer chemotherapy drugs, and the controlled deposition of functionalized nanoparticles in microfluidic devices. Recent observations of light-triggered lysosome rupture in vivo suggest the possibility that a common mechanism may underlie light-triggered vesicle explosions and lysosome rupture. http://www.jsystchem.com/content/2/1/4 Ting Zhu Jack Szostak Journal of Systems Chemistry 2011, null:4 2011-12-01T00:00:00Z doi:10.1186/1759-2208-2-4 Exploding Vesicles A dramatic phenomenon in which light triggers the sudden rupture of fatty acid vesicles has been observed in a primitive cell membrane model, and could lead to applications such as targeted drug delivery /content/figures/1759-2208-2-4-toc.gif Journal of Systems Chemistry 1759-2208 ${item.volume} 4 2011-12-01T00:00:00Z XML A self-replicating system based on a cycloaddition of a fulvene derivative and a maleinimide is investigated using a two-pronged approach combining NMR spectroscopy with computer simulations. In the course of the reaction, two diastereomers are formed with identical rates in the absence of replication. When replication is enabled, a network emerges in which one diastereomer takes over the resources as a "selfish" autocatalyst while exploiting the competitor as a weak "altruist". The structure and dynamics of the reaction network is studied using 1 D and 2 D NMR techniques supported by dynamically averaged ab initio chemical shifts and ab initio molecular dynamics simulations. It is shown that this combination is a powerful means to understand the observed experimental behaviour in great detail. http://www.jsystchem.com/content/1/1/10 Arne Dieckmann Sabrina Beniken Christian Lorenz Nikos Doltsinis Gunter von Kiedrowski Journal of Systems Chemistry 2010, null:10 2010-08-18T00:00:00Z doi:10.1186/1759-2208-1-10 /content/figures/1759-2208-1-10-toc.gif Journal of Systems Chemistry 1759-2208 ${item.volume} 10 2010-08-18T00:00:00Z XML The programmability and replicability of RNA and DNA have respectively enabled the design and selection of a number of allosteric ribozymes and deoxyribozymes. These catalysts have been adapted to function as signal transducers in biosensors and biochemical reaction networks both in vitro and in vivo. However, allosteric control of nucleic acid catalysts is currently limited by the fact that one molecule of effector (input) generally regulates at most one molecule of ribozyme or deoxyribozyme (output). In consequence, allosteric control is usually inefficient when the concentration of input molecules is low. In contrast, catalytic regulation of protein enzymes, as in protein phosphorylation cascades, generally allows one input molecule (e.g., one kinase molecule) to regulate multiple output molecules (e.g., kinase substrates). Achieving such catalytic signal amplification would also be of great utility for nucleic acid circuits. Here we show that allosteric regulation of nucleic acid enzymes can be coupled to signal amplification in an entropy-driven DNA circuit. In this circuit, kinetically trapped DNA logic gates are triggered by a specific sequence, and upon execution generate a peroxidase deoxyribozyme that converts a colorless substrate (ABTS) into a green product (ABTS•+). This scheme provides a new paradigm for the design of enzyme-free biosensors for point-of-care diagnostics. http://www.jsystchem.com/content/1/1/13 Grace Eckhoff Vlad Codrea Andrew Ellington Xi Chen Journal of Systems Chemistry 2010, null:13 2010-10-01T00:00:00Z doi:10.1186/1759-2208-1-13 /content/figures/1759-2208-1-13-toc.gif Journal of Systems Chemistry 1759-2208 ${item.volume} 13 2010-10-01T00:00:00Z XML