Genetic-algorithm selection of a regulatory structure that directs flux in a simple metabolic model.

A genetic algorithm (GA) is used to optimize parameters for allosteric regulation of enzymes in a model of a metabolic futile cycle, in which two metabolites are interconverted by a pair of irreversible enzymatic reactions. The cycle is regulated by end products of the surrounding pathway. The optimization criterion for the GA is the proper direction of chemical flux in the regulated cycle toward one or the other end product in response to a simple, time-dependent model of biochemical "need" based on externally imposed variation of the end product concentrations. An energetic cost, to be held to a minimum, is also imposed on the operation of the cycle. The best-performing individuals selected by the GA are found to switch rapidly the direction of net flux according to need. In different "environments" (specific time courses of end product concentrations), the GA produces better- or poorer-performing individuals. In some cases "generalists" and "specialists" are produced. The present approach provides, purely as a consequence of formally specifying the task of flux direction, the new result of numerical confirmation, in a simple model, of the intuition that negative feedback and reciprocal regulation are important for good flux direction in arbitrary environments, and gives rise to a diversity of structures, suggestive of the results of biological evolution.

• Publication year

  1995

• Venue

  Biophysical Journal

• Publication date

  1995-10-01

• Fields of study

  Chemistry, Medicine, Computer Science, Biology

• Identifiers
  DOI 10.1016/S0006-3495(95)79999-4PMID 8534802PMCID PMC1236362
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Computer simulated evolution of a network of cell-signaling molecules.

  1994cited by this paper
• Handbook Of Genetic Algorithms

  1990cited by this paper
• Numerical Recipes in C: The Art of Scientific Computing

  1989cited by this paper
• A theoretical approach to the evolution and structural design of enzymatic networks; Linear enzymatic chains, branched pathways and glycolysis of erythrocytes

  1987cited by this paper
• Time hierarchy in enzymatic reaction chains resulting from optimality principles.

  1987cited by this paper
• A theoretical approach to the evolution and structural design of enzymatic networks: linear enzymatic chains, branched pathways and glycolysis of erythrocytes.

  1987cited by this paper
• Enzyme structure and mechanism (2nd edn): by Alan Fersht, W. H. Freeman & Co., 1985. £14.95 pbk, £28.95 hbk (xxi + 475 pages) ISBN 0 7167 1615 1

  1985cited by this paper
• The game of the pentose phosphate cycle.

  1985cited by this paper
• Efficiency and design of simple metabolic systems.

  1985cited by this paper
• An amplified sensitivity arising from covalent modification in biological systems.

  1981cited by this paper
• Feedfoward inhibition in biosynthetic pathways: inhibition of the aminoacyl-tRNA synthetase by intermediates of the pathway.

  1979cited by this paper
• Enzyme Structure and Mechanism

  1979cited by this paper
• Feedforward inhibition in biosynthetic pathways: inhibition of the aminoacyl-tRNA synthetase by the penultimate product.

  1979cited by this paper
• Optimal design of feedback control by inhibition

  1975cited by this paper
• Optimal design of feedback control by inhibition

  1974cited by this paper

• Extreme pathway analysis reveals the organizing rules of metabolic regulation

  2019cites this paper
• Machine learning based methods for the study of metabolism and its effect on the behavior of biological systems

  2015influential citation
• Elucidating the adaptation and temporal coordination of metabolic pathways using in-silico evolution

  2014cites this paper
• Computational Intelligence in the Design of Synthetic Microbial Genetic Systems

  2013cites this paper
• Multi-Criteria Optimization of Regulation in Metabolic Networks

  2012influential citation
• Parameter Estimation Using Metaheuristics in Systems Biology: A Comprehensive Review

  2012cites this paper
• Evolutionary computation for the design of a stochastic switch for synthetic genetic circuits

  2010cites this paper
• Adaptation d'un algorithme génétique pour la reconstruction de réseaux de régulation génétique : COGARE

  2009cites this paper
• From the determination of complex reaction mechanisms to systems biology.

  2008cites this paper
• Synthetic Biology: Life, Jim, but Not As We Know It

  2008cites this paper
• A new pheromone trail-based genetic algorithm for comparative genome assembly

  2008cites this paper
• Efficient algorithms for ordinary differential equation model identification of biological systems.

  2007cites this paper
• Machine learning in bioinformatics

  2006cites this paper
• A system for studying evolution of life-like virtual organisms

  2006cites this paper
• Determination of complex reaction mechanisms. Analysis of chemical, biological and genetic networks.

  2005cites this paper
• Reverse engineering of biochemical equations from time-course data by means of genetic programming.

  2005cites this paper
• Just-in-time transcription program in metabolic pathways

  2004cites this paper
• Preliminary Studies on the In Silico Evolution of Biochemical Networks

  2004cites this paper
• Dynamic modeling of genetic networks using genetic algorithm and S-system

  2003cites this paper
• New approaches to the deduction of complex reaction mechanisms.

  2003cites this paper
• Advantages of external periodic events to the evolution of biochemical oscillatory reactions

  2003cites this paper
• Experimental test of a method for determining causal connectivities of species in reactions

  2003cites this paper
• Determination of causal connectivities of species in reaction networks

  2002cites this paper
• Genetic and Evolutionary Algorithms

  2002cites this paper
• On the deduction of chemical reaction pathways from measurements of time series of concentrations.

  2001cites this paper
• Nonlinear kinetics and new approaches to complex reaction mechanisms.

  1999cites this paper
• Optimal stoichiometric designs of ATP-producing systems as determined by an evolutionary algorithm.

  1999cites this paper
• Non-linear optimization of biochemical pathways: applications to metabolic engineering and parameter estimation

  1998cites this paper
• How did glycogen structure evolve to satisfy the requirement for rapid mobilization of glucose? A problem of physical constraints in structure building

  1997cites this paper