1. Goals Biological: Teach key biochemical principles Role of cofactors Inhibition and allosteric regulation Interactions between metabolic pathways Pedagogical: Support active learning Build mental models of biochem. processes Describe how interactions among indiv. processes yield system’s overall behavior Conduct genuine scientific investigation

2. Implementation New customizable agent shape Add/remove sites as appropriate Color-coded to allow bonding w/diff. substrates, inhibitors, etc. Each agent is assigned its own appearance and behavioral rules “complex ActR AllY CofG”

3. Glucose (substrate) NAD + (cofactor) Glycolytic Enzyme ++ Enzyme-Glucose Complex NAD + (cofactor) + k1k1 k –1 Full Reaction Complex k2k2 k –2 Enzyme-NAD + Complex Glucose (substrate) + k3k3 k –3 k4k4 k –4 2 Pyruvate (product) NADH Glycolytic Enzyme ++2 ATP+ k cat Glycolysis/Fermentation Model Similar pathway for re-oxidation of NAD + by fermentation enzymes (pyruvate  lactate)

4. Learning Objectives: Glycolysis/Fermentation Model Describe the specific roles of substrates, enzymes, and cofactors in a chemical reaction. Explain the specific role that fermentation reactions play in cellular production of ATP. Analyze the energetic cost of constitutive vs. induced expression of genes encoding fermentation enzymes. Make quantitative predictions about the direction and intensity of natural selection on these genes’ expression pattern in anaerobic environments. Repeat for aerobic environments.

5. Hb + 2 O 2 + 2 CO k –1 Hemoglobin Cooperativity Model k1k1 HbO 2 + O 2 + 2 CO k4k4 k –4 Hb(CO) + 2 O 2 + CO Hb(O 2 ) 2 + 2 CO k2k2 k –2 HbO 2 (CO) + O 2 + CO k3k3 k –3 k5k5 k –5 Hb(CO) 2 + 2 O 2 k6k6 k –6

6. Learning Objectives: Hemoglobin Cooperativity Model Describe the mechanism by which hemoglobin binds O 2, and explain how this mechanism illustrates the general principle of cooperativity. Analyze an O 2 saturation graph (w/CO present). Explain the biochemical mechanisms underlying (i) the initial rapid increase, (ii) the gradual decrease, and (iii) the small fluctuations in saturation. Combining the model results with published data, make quantitative predictions of mean lethal exposure times at different CO concentrations.

7. Next Steps In what courses would such models be useful? What relevant learning objectives might be achieved in each such course? What additional features should be added to the template (NOT to indiv. models)?