The potential of systems-based approaches are increasingly being realised in drug discovery, metabolic engineering and related areas. Developments in high-throughput experimental techniques and explosion of genomic data have fuelled progress in this area. Modelling and simulation of metabolic and regulatory pathways is an important step in systems analysis. In this review, we discuss the principles of pathway modelling, simulation techniques and current practices. A pre-requisite for modelling and simulating metabolic pathways is an accurate description of the pathway landscape. Despite availability of hundreds of annotated genome sequences, accurate information about pathways is still largely incomplete. We highlight some of the methods for deriving pathway landscapes from biochemical literature and high-throughput experimental data. The conceptual framework for modelling in terms of abstraction levels and schema for representation is also presented. Next, several classes of techniques available for modelling and simulating such systems formulated from pathway landscapes, viz. kinetic pathway modelling, interaction-based modelling and constraint-based modelling are discussed. The Systems Biology Markup Language as well as various pathway design and simulation tools are reviewed. The usefulness of various concepts and methodologies in areas such as drug discovery and metabolic engineering are illustrated with examples from literature, with a note on future perspectives.
Keywords: Systems biology, metabolic analysis, drug discovery, computational models of biochemical pathways
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