1. CZ5225 Methods in Computational BiologyLecture 9: Biological pathways and pathway simulationProf. Chen Yu ZongTel: 6874-6877Email: csccyz@nus.edu.sghttp://xin.cz3.nus.edu.sgRoom 07-24, level 7, SOC1, NUSAugust 2004

2. Biological pathways • Describe series of molecular events in living systems. • Important in understanding living systems, disease processes, effect of drugs or mutations on living systems. Annu. Rev. Biophys. Biomol. Struct. 27, 199-224 (1998)

3. Biological pathways • Map of pathways: Pathway database: KEGG http://www.genome.ad.jp/kegg/kegg2.html

4. Multiple biological pathways:Viral infection as an example How SARS coronavirus enters a cell and reproduce

5. Multiple biological pathways: Viral infection as an example Viral induced immune response: cytosine production Therapeutically relevant multiple pathways database http://xin.cz3.nus.edu.sg/group/trmp/trmp.asp

6. Multiple biological pathways: Viral infection as an example Viral induced immune response: cytosine production Therapeutically relevant multiple pathways database http://xin.cz3.nus.edu.sg/group/trmp/trmp.asp

7. Biological pathway databases Biological pathway databases: • KEGG: Kyoto Encyclopedia of Genes and Genomes. • SPAD: Signaling Pathway Database. • CSNDB: Cell Signaling Networks Database. • PFBP: Protein Function and Biochemical Pathways. Multiple pathway databases: • Therapeutically relevant multiple pathways database http://xin.cz3.nus.edu.sg/group/trmp/trmp.asp

8. Simulation of a biological pathway • Computer method appears to be the only practical approach (mainly involving no more than a few dozen proteins) dx1/dt = k1- X2 - k1+ L x1 + w1 dx2/dt = k1+ L X1 - (k1- + k2 )x2 dx3/dt = k2 X2 + k3- X5 • L = Fas ligand, x1=ligand-free Fas surface receptor, x2=ligand-bound Fas surface receptor, x3=clustered ligand-bound Fas surface receptor, x4=FADD protein, x5=complex of FADD-Fas receptor Nature Biotech. 18, 768-774 (2000)

9. Simulation of a biological pathway Quantitative description of a pathway Protein concentration and variation dx1/dt = k1- X2 - k1+ L x1 + w1 dx2/dt = k1+ L X1 - (k1- + k2 )x2 dx3/dt = k2 X2 + k3- X5 L = Fas ligand, x1=ligand-free Fas surface receptor, x2=ligand-bound Fas surface receptor, x3=clustered ligand-bound Fas surface receptor, x4=FADD protein, x5=complex of FADD-Fas receptor Nature Biotech. 18, 768-774 (2000)

10. Simulation of a biological pathway Construction of reaction/binding equations L = Fas ligand R=ligand-free Fas surface receptor ~ RL=ligand-bound Fas surface receptor RL=clustered ligand-bound Fas surface receptor Nature Biotech. 18, 768-774 (2000)

11. Simulation of a biological pathway Construction of reaction/binding kinetic equations L = Fas ligand R=ligand-free Fas surface receptor ~ RL=ligand-bound Fas surface receptor RL=clustered ligand-bound Fas surface receptor Nature Biotech. 18, 768-774 (2000)

12. Simulation of a biological pathway Nature Biotech. 18,768-774 (2000)

13. CZ5225 Methods in Computational BiologyAssignment 3