CZ5225 Methods in Computational Biology Lecture 9: Biological pathways and pathway simulation Prof. Chen Yu Zong Tel: Room 07-24, level 7, SOC1, NUS August

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, (1998)

3 Biological pathways Map of pathways: Pathway database: KEGG

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

6 Multiple biological pathways: Viral infection as an example Viral induced immune response: cytosine production Therapeutically relevant multiple pathways database

7 Biological pathway databases Biological pathway databases: KEGG: Kyoto Encyclopedia of Genes and Genomes.KEGG: Kyoto Encyclopedia of Genes and Genomes SPAD: Signaling Pathway Database.SPAD: Signaling Pathway Database CSNDB: Cell Signaling Networks Database. PFBP: Protein Function and Biochemical Pathways.PFBP: Protein Function and Biochemical Pathways Multiple pathway databases: Therapeutically relevant multiple pathways database

8 Simulation of a biological pathway Computer method appears to be the only practical approach (mainly involving no more than a few dozen proteins) Nature Biotech. 18, (2000) dx 1 /dt = k 1- X 2 - k 1+ L x 1 + w 1 dx 2 /dt = k 1+ L X 1 - (k 1- + k 2 )x 2 dx 3 /dt = k 2 X 2 + k 3- X 5 L = Fas ligand, x 1 =ligand- free Fas surface receptor, x 2 =ligand-bound Fas surface receptor, x 3 =clustered ligand-bound Fas surface receptor, x 4 =FADD protein, x 5 =complex of FADD-Fas receptor

9 Simulation of a biological pathway Quantitative description of a pathway Nature Biotech. 18, (2000) Protein concentration and variation dx 1 /dt = k 1- X 2 - k 1+ L x 1 + w 1 dx 2 /dt = k 1+ L X 1 - (k 1- + k 2 )x 2 dx 3 /dt = k 2 X 2 + k 3- X 5 L = Fas ligand, x 1 =ligand-free Fas surface receptor, x 2 =ligand-bound Fas surface receptor, x 3 =clustered ligand-bound Fas surface receptor, x 4 =FADD protein, x 5 =complex of FADD-Fas receptor

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

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

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

13 Assignment 3 CZ5225 Methods in Computational Biology Assignment 3