Michael L. Mavrovouniotis

Qualitative analysis of biochemical reaction systems

The qualitative analysis of biochemical reaction systems is presented. A discrete event systems approach is used to represent and analyze bioreaction pathways. The approach is based on Petri nets, which are particularly suited to modeling stoichiometric transformations, i.e. the inter-conversion of metabolites in fixed proportions. The properties and methods for the analysis of Petri nets, along with their interpretation for biochemical systems, are presented. As an example, the combined glycolytic and pentose phosphate pathway of the erythrocyte cell is presented to illustrate the concepts of the methodology.

Design-kit: An object-oriented environment for process engineering

Abstract This paper outlines the structure and implementational features of the DESIGN-KIT, a software support environment developed to aid process engineering activities such as: synthesis of process flowsheets, configuration of control loops for complete plants, planning and scheduling of plant-wide operations and operational analysis. Based on object-oriented and data-driven programming styles, the paper discusses how the DESIGN-KIT is constructed to provide a rich repertory of declarative and procedural knowledge for the development of analytic- or design-oriented knowledge-based expert systems. A series of illustrations describe the construction of knowledge bases, graphic interface support, equation-oriented simulation and design, order-of-magnitude analysis, reasoning strategies and other facilities of the DESIGN-KIT.

Synthesis of biochemical production routes

Abstract The problem of synthesizing biochemical pathways that satisfy linear stoichiometric constraints is discussed. An algorithm for the solution of the problem is presented, based on the iterative satisfaction of requirements, and the trasformation of the initial set of available bioreactions (which can be thought of as one-step pathways) into a final set of pathways that satisfy all the requirements. At each step, in order to satisfy a particular constraint, new pathways are constructed from pairs of existing pathways, while some of the existing pathways are deleted. The set of active pathways is thus modified to satisfy each constraint; after all constraints are processed, the remaining pathways comprise a concise description of the set of solutions. The algorithm is correct and complete and has satisfactory computational performance for carefully formulated problems.

Construction of complex reaction systems—I. Reaction description language

A new computer language has been designed to describe general types of reactions. These descriptions are used to generate the specific reactions in complex reaction systems. A wide range of reaction networks may be represented using the commands in the reaction description language (RDL). The reaction types are defined by using a sequence of commands to locate the reaction site, manipulate the reactant to form the product, and to prune the reaction network. The syntax of the language was designed to mimic the way reactions are normally described. Therefore, debugging a program written in RDL is simply a matter of proofreading. Optimization methods are employed, transparent to the user, to reorder inefficient reaction descriptions. Reaction types may be easily added, deleted, and modified to adjust the level of detail within a specific reaction network.

Construction of complex reaction systems—II. Molecule manipulation and reaction application algorithms

The modeling of complex reaction systems is necessary in the design, analysis, and control of many processes. The large number of reactants, reactions, and reaction intermediates involved make the modeling and even the description of such systems difficult. We have developed an algorithm that automatically generates complex reaction networks. The algorithm utilizes the known general types of steps to generate the mechanistic reaction network for any given feed. It is based on a specially designed computer language that can describe generic reaction sites and the generic transformation of the reactants to products. The commands in the language allow flexibility in the types of reaction systems that may be analyzed, and they may be used to adjust the level of detail of a specific reaction network. Auxiliary methods represent molecular structures, identify important substructures (such as rings), and canonicalize structures to avoid duplicates.

Construction of complex reaction systems—III. An example: alkylation of olefins

Abstract The modeling of complex reaction systems is necessary in the design and analysis of many chemical processes, such as fermentation, polymerization, and petroleum refining. We have designed a high level computer language, the Reaction Description Language, to easily and transparently describe generic reaction sites and the transformation of the reactants to products. The compiled reactions are submitted to a network generator, which iteratively applies the reactions to the reactants to form the complete reaction network. The Reaction Description Language, RDL, can be used to describe any type of reaction. Therefore, it is not limited to a specific type of reaction system. Here, we present a variety of reaction networks using reaction types from the alkylation of olefins. The effect of changing the reactants, reaction types, and pruning rules is examined.

Duality theory for thermodynamic bottlenecks in bioreaction pathways

Abstract The thermodynamic evaluation of reaction feasibility, based on the standard Gibbs energies of reaction, faces difficulties when, instead of isolated reactions, we are examining whole pathways. For pathways, we seek not only to decide whether they are feasible but also to pinpoint the pathway segment that causes thermodynamic difficulties. The obstructing pathway-segment may either be a single reaction (localized bottleneck) or a sequence of reactions (distributed bottleneck) which cannot take place simultaneously. We present a duality theory that converts the primal problem of selecting concentrations of species to make a pathway feasible to its dual problem of selecting linear combinations of reactions that make the pathway infeasible . The dual problem leads to an algorithm that can determine the thermodynamic feasibility of any chemical reaction system. The method involves the analysis of individual reactions and the selective construction of larger subpathways; it uncovers localized and distributed thermodynamic bottlenecks of a pathway. The method is applicable to reaction systems of any origin or topology, provided that concentrations of species are restricted to positive intervals.

A consistent correlation approach to single file diffusion with reaction

A method to efficiently simulate diffusion and reaction in a single-file system is presented. By considering all possible configurations of M species in a length N one-dimensional pore, a deterministic model consisting of (M+1)N variables can be constructed for the system. The order of the system can then be significantly reduced by considering only pairs of adjacent cells, or (M+1)2(N−1) doublets. This lumped model is able to capture the most important correlations between cells when the dominant mode of transport is through single-site hops. Extensions of this method for higher dimensional pores and more complex molecular interactions are discussed. The results of the approximation are compared to results of the full deterministic model, and new situations are investigated. The implications of single-file behavior are discussed for reversible reactions and molecules of different mobilities.

ESTIMATION OF UPPER BOUNDS FOR THE RATES OF ENZYMATIC REACTIONS

A general methodology that allows the estimation of maximum rates of enzymatic reactions is described. For a typical mechanism of an enzymatic reaction, the rate is a function of kinetic parameters which are unknown but required to obey certain constraints. Specifically, the ratio of forward to backward rate constants must be consistent with the equilibrium constant, and the rate of each bimolecular reaction-step must be less than the rate of collision of the two reactant species. If additional information is available on the reaction rate, more constraints can be introduced. By maximizing the rate expression with respect to the kinetic parameters, subject to all applicable constraints, a first-principles upper bound is obtained for the reaction rate. If the reaction rate is actually known, the methodology can alternatively estimate an extremum for the concentration of the enzyme, a substrate, or a product. Simple thermodynamic arguments could also provide bounds for concentrations or the direction (but n...

Rapid plant-wide screening of solvents for batch processes

Abstract The selection of suitable solvents for chemical processes requires the consideration of many kinds of information (molecular, physico-chemical, safety, health, environmental, regulatory). While experimentally-verified data is clearly the most desirable, there may be many situations in which it is neither available nor readily accessible. In these cases, the only recourse is the use of property-estimation models. We describe SMART (Solvent Measurement, Assessment and Revamping Tool), an integrated software system developed in our research group for rapidly identifying and assessing solvents for batch processes, that employs both empirical data and property-estimation methods. With respect to the latter, we also introduce a new conjugation-based method for the estimation of reaction rates in solution, useful for screening solvents to be employed as reaction media.