Biochemical Systems Analysis Instructor: Eberhard O. Voit, Ph.D. The course introduces students interested in bioinformatics and systems biology to the computational analysis of biochemical systems. It briefly reviews traditional concepts of enzyme catalyzed reactions, but places its main emphasis on modern methods of biochemical systems analysis with algebraic and computational means. The course discusses alternative modeling approaches, the design of pathway models, parameter estimation, steady states and stability, sensitivity and gain analysis, numerical evaluations of transients, phase-plane analysis, and the simulation of biomedically relevant scenarios. The theoretical concepts are applied in comprehensive case studies. Upon successful completion of the course, the student will be familiar with traditional and modern methods of enzyme kinetics and metabolic pathways. S/he will be able to design biochemical systems models from scratch and execute standard procedures of parameter estimation, steady-state analysis, and assessments of model robustness. S/he will be in a position to simulate the dynamics of metabolic pathways in response to transient and permanent perturbations. Students are expected to study the book, read additional scientific articles, and execute homework assignments and computer laboratory projects. Text: Voit, E.O.: Computational Analysis of Biochemical Systems (with software PLAS), Cambridge University Press, 2000 Grading: Two exams, one project @ 25% each Homework @ 25% (Emphasis on effort rather than correctness) Weekly Syllabus Week 1: Introduction: Issues of Reductionism and Integration; Need for Mathematical and Computational Analysis Week 2: Graphical Representation of Biochemical Systems; “Maps” Week 3: Traditional Models of Enzyme Catalyzed Reactions Week 4: Modern Models of Biochemical Systems Week 5: From Maps to Equations Week 6-7: Computer Simulation Week 8-9: Parameter Estimation Week 10: Analytical Steady-State Evaluation Week 11: Sensitivity Analysis Week 12: Case Study 1—Anaerobic Fermentation Pathway in Saccharomyces cerevisiae Week 13: Case Study 2—A Sequence of Models Describing Purine Metabolism Week 14: Case Study 3—Integration of Biochemical and Genomic Data Week 15: Related Scientific Developments