Systems biology : simulation of dynamic network states / Bernhard Ø. Palsson.

Format:

Book

Author/Creator:

Palsson, Bernhard.

Contributor:

Elizabeth Bowers Peck, 1929 Endowment Book Fund.

Language:

English

Subjects (All):

Computational biology.

Genomics.

Bioinformatics.

Physical Description:

xiii, 317 pages : illustrations ; 26 cm

Place of Publication:

Cambridge, UK ; New York : Cambridge University Press, 2011.

Summary:

Biophysical models have been used in biology for decades, but they have been limited in scope and size. In this book, Bernhard Ø. Palsson shows how network reconstructions that are based on genomic and bibliomic data, and take the form of established stoichiometric matrices, can be converted into dynamic models using metabolomic and fluxomic data. The Mass Action Stoichiometric Simulation (MASS) procedure can be used for any cellular process for which data is available and allows a scalable step-by-step approach to the practical construction of network models. Specifically, it can treat integrated processes that need explicit accounting of small molecules and proteins, which allows simulation at the molecular level. The material has been class-tested by the author at both the undergraduate and graduate level.

All computations in the text are available online in Matlab® and Mathematica® workbooks, allowing hands-on practice with the material. Book jacket.

Contents:

1 Introduction 1

1.1 Biological networks 1

1.2 Why build and study models? 5

1.3 Characterizing dynamic states 6

1.4 Formulating dynamic network models 7

1.5 The basic information is in a matrix format 11

1.6 Studying dynamic models 13

1.7 Summary 16

2 Basic concepts 17

2.1 Properties of dynamic states 17

2.2 Primer on rate laws 20

2.3 More on aggregate variables 25

2.4 Time-scale decomposition 28

2.5 Network structure versus dynamics 31

2.6 Physico-chemical effects 34

2.7 Summary 36

Part I Simulation of Dynamic States

3 Dynamic simulation: the basic procedure 41

3.1 Numerical solutions 41

3.2 Graphically displaying the solution 43

3.3 Post-processing the solution 49

3.4 Demonstration of the simulation procedure 51

3.5 Summary 56

4 Chemical reactions 58

4.1 Basic properties of reactions 58

4.2 The reversible linear reaction 60

4.3 The reversible bilinear reaction 62

4.4 Connected reversible linear reactions 66

4.5 Connected reversible bilinear reactions 70

4.6 Summary 75

5 Enzyme kinetics 76

5.1 Enzyme catalysis 76

5.2 Deriving enzymatic rate laws 78

5.3 Michaelis-Menten kinetics 80

5.4 Hill kinetics for enzyme regulation 85

5.5 The symmetry model 90

5.6 Scaling dynamic descriptions 94

5.7 Summary 96

6 Open systems 97

6.1 Basic concepts 97

6.2 Reversible reaction in an open environment 100

6.3 Michaelis-Menten kinetics in an open environment 104

6.4 Summary 107

Part II Biological Characteristics

7 Orders of magnitude 111

7.1 Cellular composition and ultra-structure 111

7.2 Metabolism 116

7.3 Macromolecules 124

7.4 Cell growth and phenotypic functions 128

7.5 Summary 131

8 Stoichiometric structure 132

8.1 Bilinear biochemical reactions 132

8.2 Bilinearity leads to a tangle of cycles 134

8.3 Trafficking of high-energy phosphate bonds 137

8.4 Charging and recovering high-energy bonds 145

8.5 Summary 149

9 Regulation as elementary phenomena 150

9.1 Regulation of enzymes 150

9.2 Regulatory signals: phenomenology 152

9.3 The effects of regulation on dynamic states 153

9.4 Local regulation with Hill kinetics 156

9.5 Feedback inhibition of pathways 161

9.6 Increasing network complexity 165

9.7 Summary 169

Part III Metabolism

10 Glycolysis 173

10.1 Glycolysis as a system 173

10.2 The stoichiometric matrix 175

10.3 Defining the steady state 181

10.4 Simulating mass balances: biochemistry 185

10.5 Pooling: towards systems biology 189

10.6 Ratios: towards physiology 199

10.7 Assumptions 202

10.8 Summary 203

11 Coupling pathways 204

11.1 The pentose pathway 204

11.2 The combined stoichiometric matrix 210

11.3 Defining the steady state 214

11.4 Simulating the dynamic mass balances 216

11.5 Pooling: towards systems biology 218

11.6 Ratios: towards physiology 219

11.7 Summary 222

12 Building networks 224

12.1 AMP metabolism 224

12.2 Network integration 231

12.3 Whole-cell models 240

12.4 Summary 241

Part IV Macromolecules

13 Hemoglobin 245

13.1 Hemoglobin: the carrier of oxygen 245

13.2 Describing the states of hemoglobin 248

13.3 Integration with glycolysis 253

13.4 Summary 257

14 Regulated enzymes 259

14.1 Phosphofructokinase 259

14.2 The steady state 265

14.3 Integration of PFK with glycolysis 269

14.4 Summary 274

15 Epilogue 275

15.1 Building dynamic models in the omics era 275

15.2 Going forward 280.

Notes:

Includes bibliographical references (pages 306-313) and index.

Local Notes:

Acquired for the Penn Libraries with assistance from the Elizabeth Bowers Peck, 1929 Endowment Book Fund.

ISBN:

1107001595

9781107001596

OCLC:

690090197

Publisher Number:

99945306250