1,721,091 research outputs found
Uniform approximation of solutions by elimination of intermediate species in deterministic reaction networks
Full text linkChemical reactions often proceed through the formation and the consumption of intermediate species. An example is the creation and subsequent degradation of the substrate-enzyme complexes in an enzymatic reaction. In this paper we provide a setting, based on ordinary differential equations, in which the presence of intermediate species has little effect on the overall dynamics of a biological system. The result provides a method to perform model reduction by elimination of intermediate species. We study the problem in a multiscale setting, where the species abundances as well as the reaction rates scale to different orders of magnitudes. The different time and concentration scales are parameterized by a single parameter N. We show that a solution to the original reaction system is uniformly approximated on compact time intervals to a solution of a reduced reaction system without intermediates and to a solution of a certain limiting reaction systems, which does not depend on N. Known approximation techniques such as the theorems by Tikhonov and Fenichel cannot readily be used in this framework
Elimination of intermediate species in multiscale stochastic reaction networks
Full text linkWe study networks of biochemical reactions modelled by continuous time Markov processes. Such networks typically contain many molecular species and reactions and are hard to study analytically as well as by simulation. Particularly, we are interested in reaction networks with intermediate species such as the substrate-enzyme complex in the Michaelis-Menten mechanism. Such species are virtually in all real-world networks, they are typically short-lived, degraded at a fast rate and hard to observe experimentally. We provide conditions under which the Markov process of a multiscale reaction network with intermediate species is approximated by the Markov process of a simpler reduced reaction network without intermediate species. We do so by embedding the Markov processes into a one-parameter family of processes, where reaction rates and species abundances are scaled in the parameter. Further, we show that there are close links between these stochastic models and deterministic ODE models of the same networks
Product-form poisson-like distributions and complex balanced reaction systems
Full text linkStochastic reaction networks are dynamical models of biochemical reaction systems and form a particular class of continuous-time Markov chains on Nn. Here we provide a fundamental characterization that connects structural properties of a network to its dynamical features. Specifically, we define the notion of "stochastically complex balanced systems" in terms of the network's stationary distribution and provide a characterization of stochastically complex balanced systems, parallel to that established in the 1970s and 1980s for deterministic reaction networks. Additionally, we establish that a network is stochastically complex balanced if and only if an associated deterministic network is complex balanced (in the deterministic sense), thereby proving a strong link between the theory of stochastic and deterministic networks. Further, we prove a stochastic version of the "deficiency zero theorem" and show that any (not only complex balanced) deficiency zero reaction network has a product-form Poisson-like stationary distribution on all irreducible components. Finally, we provide sufficient conditions for when a product-form Poisson-like distribution on a single (or all) component(s) implies the network is complex balanced, and we explore the possibility to characterize complex balanced systems in terms of product-form Poisson-like stationary distributions
Individual Molecules Dynamics in Reaction Network Models
Full text linkIn a stochastic reaction network setting we consider the problem of tracking the fate of individual molecules. We show that by using the classical large volume limit results, we may approximate the dynamics of a single tracked molecule in a simple and computationally efficient way. We give examples on how this approach may be used to obtain various characteristics of single-molecule dynamics (for instance, the distribution of the number of infections in a single individual in the course of an epidemic or the activity time of a single enzyme molecule). Moreover, we show how to approximate the overall dynamics of species of interest in the full system with a collection of independent single-molecule trajectories, and give explicit bounds for the approximation error in terms of the reaction rates. This approximation, which is well defined for all times, leads to an efficient and fully parallelizable simulation technique for which we provide some numerical examples
Graphically balanced equilibria and stationary measures of reaction networks
Full text linkThe graph-related symmetries of a reaction network give rise to certain special equilibria (such as complex balanced equilibria) in deterministic models of dynamics of the reaction network. Correspondingly, in the stochastic setting, when modeled as a continuous time Markov chain, these symmetries give rise to certain special stationary measures. Previous work by Anderson, Craciun, and Kurtz [Bull Math. Biol., 72 (2010), pp. 1947-1970] identified stationary distributions of a complex balanced network; later, Cappelletti and Wiuf [SIAM J. Appl. Math., 76 (2016), pp. 411-432] developed the notion of complex balancing for stochastic systems. We define and establish the relations between reaction balanced measure, complex balanced measure, reaction vector balanced measure, and cycle balanced measure and prove that with mild additional hypotheses, the former two are stationary distributions. Furthermore, in the spirit of an earlier work by Joshi [Discrete Contin. Dyn. Syst. Ser. B, 20 (2015), pp. 1077-1105] we give sufficient conditions under which detailed balance of the stationary distribution of Markov chain models implies the existence of positive detailed balance equilibria for the related deterministic reaction network model. Finally, we provide a complete map of the implications between balancing properties of deterministic and corresponding stochastic reaction systems, such as complex balance, reaction balance, reaction vector balance, and cycle balance
Discrepancies between extinction events and boundary equilibria in reaction networks
Full text linkReaction networks are mathematical models of interacting chemical species that are primarily used in biochemistry. There are two modeling regimes that are typically used, one of which is deterministic and one that is stochastic. In particular, the deterministic model consists of an autonomous system of differential equations, whereas the stochastic system is a continuous-time Markov chain. Connections between the two modeling regimes have been studied since the seminal paper by Kurtz (J Chem Phys 57(7):2976–2978, 1972), where the deterministic model is shown to be a limit of a properly rescaled stochastic model over compact time intervals. Further, more recent studies have connected the long-term behaviors of the two models when the reaction network satisfies certain graphical properties, such as weak reversibility and a deficiency of zero. These connections have led some to conjecture a link between the long-term behavior of the two models exists, in some sense. In particular, one is tempted to believe that positive recurrence of all states for the stochastic model implies the existence of positive equilibria in the deterministic setting, and that boundary equilibria of the deterministic model imply the occurrence of an extinction event in the stochastic setting. We prove in this paper that these implications do not hold in general, even if restricting the analysis to networks that are bimolecular and that conserve the total mass. In particular, we disprove the implications in the special case of models that have absolute concentration robustness, thus answering in the negative a conjecture stated in the literature in 2014
Node balanced steady states: Unifying and generalizing complex and detailed balanced steady states
Full text linkWe introduce a unifying and generalizing framework for complex and detailed balanced steady states in chemical reaction network theory. To this end, we generalize the graph commonly used to represent a reaction network. Specifically, we introduce a graph, called a reaction graph, that has one edge for each reaction but potentially multiple nodes for each complex. A special class of steady states, called node balanced steady states, is naturally associated with such a reaction graph. We show that complex and detailed balanced steady states are special cases of node balanced steady states by choosing appropriate reaction graphs. Further, we show that node balanced steady states have properties analogous to complex balanced steady states, such as uniqueness and asymptotic stability in each stoichiometric compatibility class. Moreover, we associate an integer, called the deficiency, to a reaction graph that gives the number of independent relations in the reaction rate constants that need to be satisfied for a positive node balanced steady state to exist. The set of reaction graphs (modulo isomorphism) is equipped with a partial order that has the complex balanced reaction graph as minimal element. We relate this order to the deficiency and to the set of reaction rate constants for which a positive node balanced steady state exists
Molecular beam scattering experiments probing the interaction of Cl2 with simple molecules (D2, O2, D2O, ND3)
No full textMolecular beam experiments for the scattering of D2, O2, D2O, and ND3 by Cl2 have been carried out to probe the involved intermolecular interaction and the quantum “glory” interference effect has been observed for all the systems. Simple and reliable interaction potentials, defined as a combination of an anisotropic van der Waals, polar flattening, charge transfer and electrostatic terms have been obtained
Stochastically modeled weakly reversible reaction networks with a single linkage class
Full text linkIt has been known for nearly a decade that deterministically modeled reaction networks that are weakly reversible and consist of a single linkage class have trajectories that are bounded from both above and below by positive constants (so long as the initial condition has strictly positive components). It is conjectured that the stochastically modeled analogs of these systems are positive recurrent. We prove this conjecture in the affirmative under the following additional assumptions: (i) the system is binary, and (ii) for each species, there is a complex (vertex in the associated reaction diagram) that is a multiple of that species. To show this result, a new proof technique is developed in which we study the recurrence properties of the n-step embedded discrete-time Markov chain
A hidden integral structure endows absolute concentration robust systems with resilience to dynamical concentration disturbances: A hidden integral structure endows absolute concentration robust systems with resilience to dynamical concentration disturbances
Full text linkBiochemical systems that express certain chemical species of interest at the same level at any positive steady state are called 'absolute concentration robust' (ACR). These species behave in a stable, predictable way, in the sense that their expression is robust with respect to sudden changes in the species concentration, provided that the system reaches a (potentially new) positive steady state. Such a property has been proven to be of importance in certain gene regulatory networks and signaling systems. In the present paper, we mathematically prove that a well-known class of ACR systems studied by Shinar and Feinberg in 2010 hides an internal integral structure. This structure confers these systems with a higher degree of robustness than was previously known. In particular, disturbances much more general than sudden changes in the species concentrations can be rejected, and robust perfect adaptation is achieved. Significantly, we show that these properties are maintained when the system is interconnected with other chemical reaction networks. This key feature enables the design of insulator devices that are able to buffer the loading effect from downstream systems - a crucial requirement for modular circuit design in synthetic biology. We further note that while the best performance of the insulators are achieved when these act at a faster timescale than the upstream module (as typically required), it is not necessary for them to act on a faster timescale than the downstream module in our construction
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