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Kosmos
Astronomia Astrofizyka
Inne

Kultura
Sztuka dawna i współczesna, muzea i kolekcje

Metoda
Metodologia nauk, Matematyka, Filozofia, Miary i wagi, Pomiary

Materia
Substancje, reakcje, energia
Fizyka, chemia i inżynieria materiałowa

Człowiek
Antropologia kulturowa Socjologia Psychologia Zdrowie i medycyna

Wizje
Przewidywania Kosmologia Religie Ideologia Polityka

Ziemia
Geologia, geofizyka, geochemia, środowisko przyrodnicze

Życie
Biologia, biologia molekularna i genetyka

Cyberprzestrzeń
Technologia cyberprzestrzeni, cyberkultura, media i komunikacja

Działalność
Wiadomości | Gospodarka, biznes, zarządzanie, ekonomia

Technologie
Budownictwo, energetyka, transport, wytwarzanie, technologie informacyjne

Journal of Systems Chemistry

Background:
The concept of an autocatalytic set of molecules has been posited theoretically and demonstrated empirically with catalytic RNA molecules. For this concept to have significance in a realistic origins-of-life scenario, it will be important to demonstrate the evolvability of such sets. Here, we employ a Gillespie algorithm to improve and expand on previous simulations of an empirical system of self-assembling RNA fragments that has the ability to spontaneously form autocatalytic networks. We specifically examine the role of serial transfer as a plausible means to allow time-dependent changes in set composition, and compare the results to equilibrium, or "batch" scenarios.
Results:
We show that the simulation model produces results that are in close agreement with the original experimental observations in terms of generating varying autocatalytic (sub)sets over time. Furthermore, the model results indicate that in a "batch" scenario the equilibrium distribution is largely determined by competition for resources and stochastic fluctuations. However, with serial transfer the system is prevented from reaching such an equilibrium state, and the dynamics are mostly determined by differences in reaction rates. This is a consistent pattern that can be repeated, or made stronger or weaker by varying the reaction rates or the duration of the transfer steps. Increasing the number of molecules in the simulation actually strengthens the potential for selection.
Conclusions:
These simulations provide a more realistic emulation of wet lab conditions using self-assembling catalytic RNAs that form interaction networks. In doing so, they highlight the potential evolutionary advantage to a prebiotic scenario that involves cyclic dehydration/rehydration events. We posit that such cyclicity is a plausible means to promote evolution in primordial autocatalytic sets, which could later lead to the establishment of individual-based biology.

http://www.jsystchem.com/content/5/1/4 2014/04/28 - 16:18

The conceptual divide separating the physical and biological sciences continues to challenge modern science. In this perspective it is proposed that the two sciences can be directly connected through the fundamental concept of stability. Physicochemical stability is shown to have a logical, rather than an empirical basis, and able to manifest itself in two distinct and often contrary ways, one thermodynamic, reflecting energetic considerations, and the other kinetic, reflecting time/persistence considerations. Each stability kind is shown to rest on a particular mathematical truism. Thermodynamic stability, the energetic expression, has a probabilistic/statistical basis due to Boltzmann, and leads to the Second Law of Thermodynamics. Dynamic kinetic stability (DKS), the time/persistence expression, is attributed to the stability associated with persistent replicating systems, and derives from the mathematics of exponential growth. The existence of two distinct stability kinds, each mathematically-based, leads to two distinct organizational forms of matter, animate and inanimate. That understanding offers insight into the reasons for the observation of just those two organizational forms, their different material characteristics, and provides a logical basis for understanding the nature of chemical and biological transformations, both within, and between, the two forms.

http://www.jsystchem.com/content/5/1/3 2014/03/29 - 19:08

Background:
In previous work, RAF theory has been developed as a tool for making theoretical progress on theorigin of life question, providing insight into the structure and occurrence of self-sustaining and collectivelyautocatalytic sets within catalytic polymer networks. We present here an extension in whichthere are two "independent" polymer sets, where catalysis occurs within and between the sets, butthere are no reactions combining polymers from both sets. Such an extension reflects the interactionbetween nucleic acids and peptides observed in modern cells and proposed forms of early life.
Results:
We present theoretical work and simulations which suggest that the occurrence of autocatalytic sets isrobust to the partitioned structure of the network. We also show that autocatalytic sets remain likelyeven when the molecules in the system are not polymers, and a low level of inhibition is present.Finally, we present a kinetic extension which assigns a rate to each reaction in the system, and showthat identifying autocatalytic sets within such a system is an NP-complete problem.
Conclusions:
Recent experimental work has challenged the necessity of an RNA world by suggesting that peptidenucleicacid interactions occurred early in chemical evolution. The present work indicates that sucha peptide-RNA world could support the spontaneous development of autocatalytic sets and is thus afeasible alternative worthy of investigation.

http://www.jsystchem.com/content/5/1/2 2014/03/03 - 23:09

Background:
Multidisciplinary consensus indicates that half of the genetically amino acids are likely to have been available on the prebiotic earth, which implies certain adaptive expectations for the relationship between those amino acids and later additions to the genetic code. Chemistry space a concept that translates molecules to corresponding points in multidimensional space provides a framework for investigating these relationships. We therefore developed three tests to explore these implications using chemistry space to quantify otherwise qualitative questions.
Results:
All three of our tests individually, as well as combined, provide quantitative evidence to support an adaptive expansion of the genetically encoded amino acid alphabet from 10 prebiotically plausible ("early") amino acids to the full set of 20 amino acids found within the standard genetic code.
Conclusions:
We present three logically independent, novel tests of the adaptive growth of the amino acid alphabet from a smaller, functionally cohesive alphabet of only 10 amino acids to the 20 amino acids of the standard genetic code. While similar tests in the past have compared the genetically encoded amino acids to an external context of amino acids that were not incorporated into the genetic code our tests focus on the internal context of the 20 genetically encoded amino acids and find strong support. Of particular note one of these tests for the first time moves beyond consideration of amino acids as monomers and begins to explore polypeptides by considering the chemistry space of amino acid dimers.

http://www.jsystchem.com/content/5/1/1 2014/01/22 - 16:41

Background:
Modeling molecules as undirected graphs and chemical reactions as graph rewriting operations is anatural and convenient approach to modeling chemistry. Graph grammar rules are most naturallyemployed to model elementary reactions like merging, splitting, and isomerisation of molecules. Itis often convenient, in particular in the analysis of larger systems, to summarize several subsequentreactions into a single composite chemical reaction.
Results:
We introduce a generic approach for composing graph grammar rules to define a chemically usefulrule compositions. We iteratively apply these rule compositions to elementary transformationsin order to automatically infer complex transformation patterns. As an application we automaticallyderive the overall reaction pattern of the Formose cycle, namely two carbonyl groups that can reactwith a bound glycolaldehyde to a second glycolaldehyde. Rule composition also can be used to studypolymerization reactions as well as more complicated iterative reaction schemes. Terpenes and thepolyketides, for instance, form two naturally occurring classes of compounds of utmost pharmaceuticalinterest that can be understood as "generalized polymers" consisting of five-carbon (isoprene) andtwo-carbon units, respectively.
Conclusion:
The framework of graph transformations provides a valuable set of tools to generate and investigatelarge networks of chemical networks. Within this formalism, rule composition is a canonical techniqueto obtain coarse-grained representations that reflect, in a natural way, "effective" reactions thatare obtained by lumping together specific combinations of elementary reactions.

http://www.jsystchem.com/content/4/1/4 2013/06/07 - 10:18

Background The idea that autocatalytic sets played an important role in the origin of life is not new. However, the likelihood of autocatalytic sets emerging spontaneously has long been debated. Recently, progress has been made along two different lines. Experimental results have shown that autocatalytic sets can indeed emerge in real chemical systems, and theoretical work has shown that the existence of such self-sustaining sets is highly likely in formal models of chemical systems. Here, we take a first step towards merging these two lines of work by constructing and investigating a formal model of a real chemical system of RNA replicators exhibiting autocatalytic sets.Results We show that the formal model accurately reproduces recent experimental results on an RNA replicator system, in particular how the system goes through a sequence of larger and larger autocatalytic sets, and how a cooperative (autocatalytic) system can outcompete an equivalent selfish system. Moreover, the model provides additional insights that could not be obtained from experiments alone, and it suggests several experimentally testable hypotheses.ConclusionsGiven these additional insights and predictions, the modeling framework provides a better and more detailed understanding of the nature of chemical systems in general and the emergence of autocatalytic sets in particular. This provides an important first step in combining experimental and theoretical work on autocatalytic sets in the context of the orgin of life.

http://www.jsystchem.com/content/4/1/3 2013/02/27 - 01:51

Background:
The assessment of molecular similarity is a key step in the drug discovery process that has thus far relied almost exclusively on computational approaches. We now report an experimental method for similarity assessment based on dynamic combinatorial chemistry.
Results:
In order to assess molecular similarity directly in solution, a dynamic molecular network was used in a two-step process. First, a clustering analysis was employed to determine the network's innate discriminatory ability. A classification algorithm was then trained to enable the classification of unknowns. The dynamic molecular network used in this work was able to identify thin amines and ammonium ions in a set of 25 different, closely related molecules. After training, it was also able to classify unknown molecules based on the presence or absence of an ethylamine group.
Conclusions:
This is the first step in the development of molecular networks capable of predicting bioactivity based on an assessment of molecular similarity.

http://www.jsystchem.com/content/4/1/2 2013/02/13 - 06:31

The hypercycle is a system of replicators, whose members are auto- and cross-catalytic: replication of each member is catalyzed by at least one other member of the system. Therefore, the kinetics of growth of every member is at least second order. In ecology such systems are called mutualistic whose members are cooperating with each other. The dynamics of such systems are described broadly by the replicator equation. In chemistry hypercycles are often confused with collectively autocatalytic systems in which the members catalyze each other's formation rather than replication (growth being therefore first-order). Examples of this confusion abound in the literature. The trouble is that such category errors mistakenly imply that the available theories of hypercycles and cooperation are applicable, although in fact they are not. Cooperation in population biology means a higher-order interaction among agents with (at least the capacity of) multiplication. From the point of evolution, what matters is the genetic effects on the cooperative act. As systems chemistry has one of its roots in the theoretical biology, insights from this field ought to be respected even by experimentalists, let alone theoreticians.

http://www.jsystchem.com/content/4/1/1 2013/02/12 - 07:09

Any living organism can be considered as a component of a dissipative process coupling an irreversible consumption of energy to the growth, reproduction and evolution of living things. Close interactions between metabolism and reproduction are thus required, which means that metabolism has two main functions. The first one, which is the most easily perceptible, corresponds to the synthesis of the components of living beings that are not found in the environment (anabolism). The second one, which is usually associated with the former, is the dissipative process coupling the consumption of energy to self-organization and reproduction and introducing irreversibility in the process. Considering the origin of life, the formation of at least some of the building blocks constituting a living organism can be envisaged in a close to equilibrium situation under reducing conditions (for instance in hydrothermal vents). However, coupling irreversibly self-organization with the dissipation of an energy flux implies far from equilibrium conditions that are shown in this work to raise quantitative requirements on the height of kinetic barriers protecting metabolites from a spontaneous evolution into deactivated species through a quantitative relationship with the time scale of the progress of the overall process and the absolute temperature. The thermodynamic potential of physical sources of energy capable of feeding the emergence of this capacity can be inferred, which leads to the identification of photochemistry at the wavelength of visible light or processes capable of generating activated species by heating transiently a chemical environment above several thousand Kelvin as the only processes capable of fulfilling this requirement.

http://www.jbppni.com/content/3/1/3 2012/12/05 - 11:13

Background:
Autocatalytic sets are often considered a necessary (but not sufficient) condition for theorigin and early evolution of life. Although the idea of autocatalytic sets was alreadyconceived of many years ago, only recently have they gained more interest, followingadvances in creating them experimentally in the laboratory. In our own work, we havestudied autocatalytic sets extensively from a computational and theoretical point of view.
Results:
We present results from an initial study of the dynamics of self-sustaining autocatalytic sets(RAFs). In particular, simulations of molecular flow on autocatalytic sets are performed, toillustrate the kinds of dynamics that can occur. Next, we present an extension of our(previously introduced) algorithm for finding autocatalytic sets in general reactionnetworks, which can also handle inhibition. We show that in this case detectingautocatalytic sets is fixed parameter tractable. Finally, we formulate a generalized version ofthe algorithm that can also be applied outside the context of chemistry and origin of life,which we illustrate with a toy example from economics.
Conclusions:
Having shown theoretically (in previous work) that autocatalytic sets are highly likely toexist, we conclude here that also in terms of dynamics such sets are viable and outcompetenon-autocatalytic sets. Furthermore, our dynamical results confirm arguments made earlierabout how autocatalytic subsets can enable their own growth or give rise to other suchsubsets coming into existence. Finally, our algorithmic extension and generalization show that more realistic scenarios (e.g., including inhibition) can also be dealt with within ourframework, and that it can even be applied to areas outside of chemistry, such as economics.

http://www.jsystchem.com/content/3/1/5 2012/08/14 - 16:31

Background:
Autocatalytic sets are often considered a necessary (but not sufficient) condition for theorigin and early evolution of life. Although the idea of autocatalytic sets was alreadyconceived of many years ago, only recently have they gained more interest, followingadvances in creating them experimentally in the laboratory. In our own work, we havestudied autocatalytic sets extensively from a computational and theoretical point of view.
Results:
We present results from an initial study of the dynamics of self-sustaining autocatalytic sets(RAFs). In particular, simulations of molecular flow on autocatalytic sets are performed, toillustrate the kinds of dynamics that can occur. Next, we present an extension of our(previously introduced) algorithm for finding autocatalytic sets in general reactionnetworks, which can also handle inhibition. We show that in this case detectingautocatalytic sets is fixed parameter tractable. Finally, we formulate a generalized version ofthe algorithm that can also be applied outside the context of chemistry and origin of life,which we illustrate with a toy example from economics.
Conclusions:
Having shown theoretically (in previous work) that autocatalytic sets are highly likely toexist, we conclude here that also in terms of dynamics such sets are viable and outcompetenon-autocatalytic sets. Furthermore, our dynamical results confirm arguments made earlierabout how autocatalytic subsets can enable their own growth or give rise to other suchsubsets coming into existence. Finally, our algorithmic extension and generalization show that more realistic scenarios (e.g., including inhibition) can also be dealt with within ourframework, and that it can even be applied to areas outside of chemistry, such as economics.

http://www.jsystchem.com/content/3/1/5 2012/08/14 - 16:31

Background:
Many biological systems contain complex precipitation patterns. These structures are considered to be the result of finely tuned and genetically encoded developmental pathways. The amount of encoded information needed to generate and manipulate these structures is poorly understood. Investigating the dynamics of spontaneous pattern formation in non-biological systems provides insights to the physio-chemical phenomena that biological systems must have harnessed for living systems and that modern scientists need to understand for complex nano-technological applications
Results:
Here we show that highly complex, precipitation patterns similar to those found in biological systems can be formed in simple Cu(II)-oxalate systems. In these Cu(II)-oxalate systems, structures are constructed by a hierarchy of multiple processes that are precisely self-organized in space and time to form interconnected causal networks that generate complex and diverse structures dependent on construction trajectories that can be controlled by minor variations of initial conditions.
Conclusions:
Highly complex precipitation patterns similar to those found in biological systems can be generated without a correspondingly complex set of instructions. Our result has implications for understanding early biotic systems that existed prior to the evolution of sophisticated genetic machinery. From an applications perspective, processes and structures that occur spontaneously are the building blocks for novel system chemistry based technologies where products are self-constructed. We also provide a simple model of chemical system that generates biomimetic structures for the study of fundamental processes involved in chemical self-construction.

http://www.jsystchem.com/content/3/1/4 2012/08/03 - 11:43

Any living organism can be considered as a component of a dissipative process coupling anirreversible consumption of energy to the growth, reproduction and evolution of living things.Close interactions between metabolism and reproduction are thus required, which means thatmetabolism has two main functions. The first one, which is the most easily perceptible,corresponds to the synthesis of the components of living beings that are not found in theenvironment (anabolism). The second one, which is usually associated with the former, is thedissipative process coupling the consumption of energy to self-organization and reproductionand introducing irreversibility in the process. Considering the origin of life, the formation ofat least some of the building blocks constituting a living organism can be envisaged in a closeto equilibrium situation under reducing conditions (for instance in hydrothermal vents).However, coupling irreversibly self-organization with the dissipation of an energy fluximplies far from equilibrium conditions that are shown in this work to raise quantitativerequirements on the height of kinetic barriers protecting metabolites from a spontaneousevolution into deactivated species through a quantitative relationship with the time scale ofthe progress of the overall process and the absolute temperature. The thermodynamicpotential of physical sources of energy capable of feeding the emergence of this capacity canbe inferred, which leads to the identification of photochemistry at the wavelength of visiblelight or processes capable of generating activated species by heating transiently a chemicalenvironment above several thousand Kelvin as the only processes capable of fulfilling thisrequirement.

http://www.jsystchem.com/content/3/1/3 2012/05/17 - 23:16

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 2012/02/04 - 06:45

Background:
A classical problem in metabolic design is to maximize the production of a desired compound in a given chemical reaction network by appropriately directing the mass flow through the network. Computationally, this problem is addressed as a linear optimization problem over the "flux cone''. The prior construction of the flux cone is computationally expensive and no polynomial-time algorithms are known.
Results:
Here we show that the output maximization problem in chemical reaction networks is NP-complete. This statement remains true even if all reactions are monomolecular or bimolecular and if only a single molecular species is used as influx. As a corollary we show, furthermore, that the detection of autocatalytic species, i.e., types that can only be produced from the influx material when they are present in the initial reaction mixture, is an NP-complete computational problem.
Conclusions:
Hardness results on combinatorial problems and optimization problems are important to guide the development of computational tools for the analysis of metabolic networks in particular and chemical reaction networks in general. Our results indicate that efficient heuristics and approximate algorithms need to be employed for the analysis of large chemical networks since even conceptually simple flow problems are provably intractable.

http://www.jsystchem.com/content/3/1/1 2012/01/07 - 16:06

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 2011/12/02 - 06:15

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 uM. 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 2011/10/04 - 20:48

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 2011/06/23 - 17:08

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 2011/06/08 - 06:23

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 2011/01/22 - 13:57

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 2011/01/22 - 13:57

The mathematical form of the energy-entropy relationship is that of the relationship between the difference and the ratio of any two 'entities' x and y creating a geometrical 3D projection x = y·z, i.e., a surface of the shape of a hyperbolic paraboloid being a particular form of a quadric. The significance of this relationship is discussed here in a realm beyond thermodynamics. Somewhat intuitively, yet still in strict mathematical analogy to the relation between its most fundamental state variables, I propose for any isolated universe the cosmological state variables, absolute temperature and absolute time, to be equivalent much in the same way as energy and entropy are equivalent for an isolated ensemble of similar objects. According to this principle, the cosmological constant is inversely proportional to the squared product of absolute time and absolute temperature. The spontaneous symmetry breaking into a time component and a temperature component of the universe takes place when the first de facto irreversible movement occurs owing to a growing accessed total volume.

http://www.jsystchem.com/content/1/1/11 2011/01/22 - 13:57

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 2011/01/22 - 13:57

Background:
The "RNA World" hypothesis suggests that an early form of life on Earth was based on nucleic acid strands able to store genetic information and catalyze a wide range of reactions including those which lead to self-replication. For this hypothesis to be true there must exist an efficient process for creating RNA or RNA-like polymers of mixed sequences from short precursors, where these polymers have to be long enough to fold into catalytically active structures (at least 40 bases).
Results:
We report on the polymerization of dimeric to hexameric 5'-amino- oligodeoxynucleotides 3'-phosphates in the presence of the water-soluble carbodiimide EDC. Non-complementary single stranded nucleotides fail to polymerize and yield di- to hexameric cyclooligomers or capped EDC-adducts unable to undergo further 3'-5'-phosphoramidate formation. Complementary building blocks polymerize with a conversion close to 100% when starting from a concentration of typically 20 mM. The reactions proceed within a few hours yielding strands of mixed pyrimidine-purine sequences up to 300 bases long. The maximum length of the products depends on the type of the starting oligonucleotides. Copolymerization of a dimer alphabet consisting of equimolar quantities of all four sequences d(nYRp), where Y are pyrimidines and R are purines, generates a mixed-sequence library of 50-70 mers.
Conclusions:
Libraries of long oligonucleotides with potentially catalytic activity are formed from short precursors within hours. Reactions occur via blunt end ligation of the double strands, and the reaction rates correlate with stacking interactions at the ligation sites. Circular dichroism measurements, polarized light microscopy and fluorescence microscopy suggest the formation of supramolecular aggregates during chain growth. These aggregates accelerate the reactions by increasing the local concentration of the reactants in a non-sequence-specific templating mode. Aggregation of the double strands into higher order "compartimented" structures might have been the key for the formation of the first inhabitants of the "RNA World".

http://www.jsystchem.com/content/1/1/9 2011/01/22 - 13:57

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 2011/01/22 - 13:57

In earlier studies, we showed that certain low-molecular-weight carboxylic acids (profens, amino acids, hydroxy acids) can undergo spontaneous in vitro chiral conversion accompanied by condensation to from oligomers, and we proposed two simple models to describe these processes. Here, we present the results of investigations using non-chiral high-performance liquid chromatography with diode array detector (HPLC-DAD) and mass spectrometry (MS) on the dynamics of peptidization of S-, R-, and rac-phenylglycine dissolved in 70% aqueous ethanol and stored for times up to one year. The experimental results demonstrate that peptidization of phenylglycine can occur in an oscillatory fashion. We also describe, and carry out simulations with, three models that capture key aspects of the oscillatory condensation and chiral conversion processes.

http://www.jsystchem.com/content/1/1/7 2011/01/22 - 13:57

We describe the stepwise construction of an 8-component self-sorted system (1 - 8) by the sequential addition of components. This process occurs via a large number of states (28 = 256) and even a larger number of pathways (8! = 40320). A pathway (5, 6, 7, 8, 4, 3, 2, then 1) that is self-sorted at every step along the way has been demonstrated experimentally. Another pathway (1, 8, 3, 5, 4, 7, 2, then 6) resembles a game of musical chairs and exhibits interesting shuttling of guest molecules among hosts. The majority of pathways - unlike the special ones described above - proceed through several non self-sorted states. We characterized the remainder of the 40320 pathways by simulation using Gepasi and describe the influence of concentration and binding constants on the fidelity of the self-sorting pathways.

http://www.jsystchem.com/content/1/1/6 2011/01/22 - 13:57

The origin of homochirality of organic compounds such as L-amino acids and D-sugars have intrigued many scientists, and several hypotheses regarding its homochirality have been proposed. According to the statistical theory, small fluctuations in the ratio of the two enantiomers are present in a racemic mixture obtained from the reaction of achiral molecules.We report herein the reaction of pyrimidine-5-carbaldehyde and diisopropylzinc in the presence of achiral amine such as N,N'-dimethylpiperazine, N,N'-diethylpiperazine or N-methylmorpholine but in the absence of a chiral substance. The stochastic formation of (S)- and (R)-pyrimidyl alkanols with detectable ee was observed. This study shows that the slight fluctuation of the enantiomeric ratio of pyrimidyl alkanol produced at the initial reaction step can be enhanced significantly in conjunction with asymmetric autocatalysis with amplification of enantiomeric excess. We believe that the stochastic behavior in the formation of pyrimidyl alkanol constitutes one of the conditions necessary for spontaneous absolute asymmetric synthesis.

http://www.jsystchem.com/content/1/1/5 2011/01/22 - 13:57

Background:
The metabolic architectures of extant organisms share many key pathways such as the citric acid cycle, glycolysis, or the biosynthesis of most amino acids. Several competing hypotheses for the evolutionary mechanisms that shape metabolic networks have been discussed in the literature, each of which finds support from comparative analysis of extant genomes. Alternatively, the principles of metabolic evolution can be studied by direct computer simulation. This requires, however, an explicit implementation of all pertinent components: a universe of chemical reactions upon which the metabolism is built, an explicit representation of the enzymes that implement the metabolism, a genetic system that encodes these enzymes, and a fitness function that can be selected for.
Results:
We describe here a simulation environment that implements all these components in a simplified way so that large-scale evolutionary studies are feasible. We employ an artificial chemistry that views chemical reactions as graph rewriting operations and utilizes a toy-version of quantum chemistry to derive thermodynamic parameters. Minimalist organisms with simple string-encoded genomes produce model ribozymes whose catalytic activity is determined by an ad hoc mapping between their secondary structure and the transition state graphs that they stabilize. Fitness is computed utilizing the ideas of metabolic flux analysis. We present an implementation of the complete system and first simulation results.
Conclusions:
The simulation system presented here allows coherent investigations into the evolutionary mechanisms of the first steps of metabolic evolution using a self-consistent toy universe.

http://www.jsystchem.com/content/1/1/4 2011/01/22 - 13:57