1Department of Biological Chemistry (2008)
Mariette R. Atkinson, Gardner Et Al, Michael A. Savageau, Jesse T. Myers, Er J. Ninfa
toggle switch, consisting of two repressors that control each other’s expression, demonstrated bistability and hysteresis (Gardner et al., 2000). The oscillator, consisting of three genes encoding...
Oosawa, Chikoo, Savageau, Michael A., Jarrah, Abdul S., Laubenbacher, Reinhard C., Sontag, Eduardo D.
We demonstrate the effects of embedding subgraphs using a Boolean network, which is one of the discrete dynamical models for transcriptional regulatory networks. After comparing the dynamical...
Oosawa, Chikoo, Takemoto, Kazuhiro, Savageau, Michael A.
We demonstrate the advantages of feedforward loops using a Boolean network, which is one of the discrete dynamical models for transcriptional regulatory networks. After comparing the dynamical...
Local cause of coherence in Boolean networks (2006)
Oosawa, Chikoo, Takemoto, Kazuhiro, Matsumoto, Shogo, Savageau, Michael A.
We performed a numerical study on random Boolean networks with power-law rank outdegree distributions to find local structural cause for the emergence of high or low degree of coherence in binary...
Some properties of the Lerch family of discrete distributions (2005)
Aksenov, Sergej V., Savageau, Michael A.
We extend the definition of the Lerch distribution to the set of nonnegative integers for greater applicability to modeling count data. We express its properties in terms of Lerch's transcendent, and...
Statistical inference and modeling with the S distribution (2001)
Aksenov, Sergej V., Savageau, Michael A.
We consider the problem of statistical inference for the S distribution and introduce new minimum distance estimators for the four parameters of the S distribution using Kolmogorov-Smirnov,...
Alves, Rui, Savageau, Michael A.
Motivation: When dealing with questions that concern a general class of models for biological networks, large numbers of distinct models within the class can be grouped into an ensemble that gives a...
Alves, Rui, Savageau, Michael A.
Motivation: Mathematical models are the only realistic method for representing the integrated dynamic behavior of complex biochemical networks. However, it is difficult to obtain a consistent set of...
Extending the method of mathematically controlled comparison to include numerical comparisons (2000)
Alves, Rui, Savageau, Michael A.
Motivation: The method of mathematically controlled comparison has been used for some time to determine which of two alternative regulatory designs is better according to specific quantitative...
Selection and Computational Potential of Gene Control Elements and Their Circuitry (1998)
The physical basis for biological complexity is context-dependent expression of the organism's genome. The context is provided by the life cycle of the organism; the molecular mechanisms of gene...
Influence of fractal kinetics on molecular recognition (1993)
Molecular recognition is a central issue for nearly every biological mechanism. The analysis of molecular recognition to has been conducted within the framework of classical chemical kinetics, in...
Finding multiple roots of nonlinear algebraic equations using s-system methodology (1993)
The solution of nonlinear algebraic equations is a well-known problem in many fields of science and engineering. Several types of numerical methods exist, each with their advantages and...
Sorribas, Albert, Savageau, Michael A.
The need for a well-structured theory of intact biochemical systems becomes increasingly evident as one attempts to integrate the vast knowledge of individual molecular constituents, which has been...
Sorribas, Albert, Savageau, Michael A.
In the past two decades, several theories, all ultimately based upon the same power-law formalism, have been proposed to relate the behavior of intact biochemical system to the properties of their...
Sorribas, Albert, Savageau, Michael A.
The search for systematic methods to deal with the integrated behavior of complex biochemical systems has over the past two decades led to the proposal of several theories of biochemical systems....
Peer Reviewed
Introduction to S-systems and the underlying power-law formalism (1988)
A novel approach to the development of an appropriate formalism for representing organizationally complex systems began in the mid 1960's with a search for a general systematic formalism that would...
Recasting nonlinear differential equations as S-systems: a canonical nonlinear form (1987)
Savageau, Michael A., Voit, Eberhard O.
An enormous variety of nonlinear differential equations and functions have been recast exactly in the canonical form called an S-system. This is a system of nonlinear ordinary differential equations,...
Savageau, Michael A., Voit, Eberhard O., Irvine, Douglas H.
Biochemical Systems Theory (BST) was developed in the late 1960s to explicate the integrated behavior of intact biochemical systems--specific dynamic behavior as well as general principles of...
Savageau, Michael A., Voit, Eberhard O., Irvine, Douglas H.
Perhaps the major obstacle to recognizing the relatedness of Biochemical Systems Theory (BST) and a subsequently developed approach some have called Metabolic Control Theory (MCT) is the summation...
Equivalence between S-systems and Volterra systems (1986)
Voit, Eberhard O., Savageau, Michael A.
S-systems and Volterra systems have been developed independently of each other in different branches of biology. We show that these systems are mathematically equivalent.
Analytical solutions to a generalized growth equation (1984)
Voit, Eberhard O., Savageau, Michael A.
Systems of the form occur in the analysis of biological networks. They also include as special cases the known growth laws and probability functions, famous differential equations like those of...
RNA splicing: Advantages of parallel processing (1982)
Von Heijne, Gunnar, Savageau, Michael A.
Parallel and sequential modes of RNA processing are systematically compared by an analysis of the relevant kinetic reaction schemes. The parallel mode is shown to be superior in the sense that it...
Savageau, Michael A., Lapointe, David S.
We have previously presented a general cost-accuracy relationship for a broad class of kinetic proofreading mechanisms. In this paper we present a general matrix method, based upon classical enzyme...
Accuracy of proofreading with zero energy cost (1981)
Accuracy of biological discrimination at the molecular level is known in some systems to involve kinetic proofreading mechanisms. Hopfield and Ninio were the first to propose simple specific kinetic...
Proofreading systems of multiple stages for improved accuracy of biological discrimination (1980)
Freter, Rolf R., Savageau, Michael A.
The phenomenal accuracy of biological discrimination is due in many cases to specific proofreading mechanisms. We have previously developed a macroscopic theory of such mechanisms and applied it to...
Growth equations: A general equation and a survey of special cases (1980)
Although growth in its various manifestations has been studied for centuries and although there are a large number of well-established growth "laws," that work is almost entirely empirical and lacks...
Dery, Charlotte, Cooper, Stephen, Savageau, Michael A., Scanlon, Sarah
Contrary to previous reports, we find the molecular weight of the major cAMP-binding protein in to be 54,000 daltons. A number of lower molecular weight proteins have also been identified and are...
Inhibition of the aminoacyl-tRNA synthetase by the penultimate product of a pathway for the biosynthesis of an amino acid has been reported for several pathways in many different types of organisms....
Savageau, Michael A., Jacknow, Gerald
The stability of an amino acid biosynthetic pathway controlled by end-product inhibition is significantly improved if, in addition, the corresponding aminoacyl-tRNA synthetase is inhibited by an...
Bochner, Barry R., Savageau, Michael A.
Imidazole propionic acid (ipa), a gratuitous inducer of the histidine-utilization ( hut ) system in Salmonella typhimurium , inhibits the organism's growth on succinate minimal medium. Induction of...
Optimal design of feedback control by inhibition (1975)
The local stability of unbranched biosynthetic pathways is examined by mathematical analysis and computer simulation using a novel nonlinear formalism that appears to accurately describe biochemical...
Optimal design of feedback control by inhibition (1974)
A recently developed, nonlinear method of systems analysis has been used to compare alternative patterns of control by feedback inhibition in otherwise equivalent unbranched biosynthetic pathways....
Savageau, Michael A., Kotre, Ann Marie, Sakamoto, Naoto
Both glutamine: [alpha]-ketoglutarate amidotransferase and glutamate dehydrogenase activities are obtained from grown in minimal medium containing glucose and ammonia. These activities are not...
Templeton, Bonnie A., Savageau, Michael A.
Homoserine is transported by a single system that it shares with alanine, isoleucine, leucine, phenylalanine, threonine, valine and perhaps cysteine, methionine, serine, and tyrosine. We investigated...
Transport of Biosynthetic Intermediates: Homoserine and Threonine Uptake in Escherichia coli
Templeton, Bonnie A., Savageau, Michael A.
Although amino acid transport has been extensively studied in bacteria during the past decade, little is known concerning the transport of those amino acids that are biosynthetic intermediates or...
Salvador, Armindo, Savageau, Michael A.
Why do the activities of some enzymes greatly exceed the flux capacity of the embedding pathways? This is a puzzling open problem in quantitative evolutionary design. In this work we investigate...
Metabolic Regulation by Homoserine in Escherichia coli B/r
Kotre, Ann M., Sullivan, Stephen J., Savageau, Michael A.
A mathematical analysis of branched pathway regulation has led to the prediction of a novel homoserine control in Escherichia coli B. Experimental support for such control is presented in this paper....
Genetic Regulatory Mechanisms and the Ecological Niche of Escherichia coli
Whether the regulatory protein of an inducible operon for a catabolic pathway is a positive or a negative element in the control of expression is correlated with the frequent or infrequent presence,...
Growth of complex systems can be related to the properties of their underlying determinants
Growth—increase in size, number, or amount—in many cases appears to follow simple empirical laws. Such laws have been noted in a wide variety of fields for many years. Until now these laws have...
Allometric morphogenesis is the generation of form or pattern as a result of differential growth according to power-law relationships among the elements of a complex system. This phenomenon has been...
Evolution of enzymes in a series is driven by dissimilar functional demands
Salvador, Armindo, Savageau, Michael A.
That distinct enzyme activities in an unbranched metabolic pathway are evolutionarily tuned to a single functional requirement is a pervasive assumption. Here we test this assumption by examining the...
Templeton, Bonnie A., Savageau, Michael A.
Homoserine is transported by a single system that it shares with alanine, isoleucine, leucine, phenylalanine, threonine, valine and perhaps cysteine, methionine, serine, and tyrosine. We investigated...
Transport of Biosynthetic Intermediates: Homoserine and Threonine Uptake in Escherichia coli
Templeton, Bonnie A., Savageau, Michael A.
Although amino acid transport has been extensively studied in bacteria during the past decade, little is known concerning the transport of those amino acids that are biosynthetic intermediates or...
Salvador, Armindo, Savageau, Michael A.
Why do the activities of some enzymes greatly exceed the flux capacity of the embedding pathways? This is a puzzling open problem in quantitative evolutionary design. In this work we investigate...
Metabolic Regulation by Homoserine in Escherichia coli B/r
Kotre, Ann M., Sullivan, Stephen J., Savageau, Michael A.
A mathematical analysis of branched pathway regulation has led to the prediction of a novel homoserine control in Escherichia coli B. Experimental support for such control is presented in this paper....
Genetic Regulatory Mechanisms and the Ecological Niche of Escherichia coli
Whether the regulatory protein of an inducible operon for a catabolic pathway is a positive or a negative element in the control of expression is correlated with the frequent or infrequent presence,...
Growth of complex systems can be related to the properties of their underlying determinants
Growth—increase in size, number, or amount—in many cases appears to follow simple empirical laws. Such laws have been noted in a wide variety of fields for many years. Until now these laws have...
Allometric morphogenesis is the generation of form or pattern as a result of differential growth according to power-law relationships among the elements of a complex system. This phenomenon has been...
Evolution of enzymes in a series is driven by dissimilar functional demands
Salvador, Armindo, Savageau, Michael A.
That distinct enzyme activities in an unbranched metabolic pathway are evolutionarily tuned to a single functional requirement is a pervasive assumption. Here we test this assumption by examining the...
Quantifying Global Tolerance of Biochemical Systems: Design Implications for Moiety-Transfer Cycles
Salvador, Armindo, Savageau, Michael A.
Robustness of organisms is widely observed although difficult to precisely characterize. Performance can remain nearly constant within some neighborhood of the normal operating regime, leading to...
Phenotypes and tolerances in the design space of biochemical systems
Savageau, Michael A., Fasani, Rick A., Tolla, Dean A., Salvador, Armindo
One of the major unsolved problems of modern biology is deep understanding of the complex relationship between the information encoded in the genome of an organism and the phenotypic properties...