Biomolecular computing systems represent a rapidly developing research field and is covered in this book by the major contributors in the field by overviewing the the state-of-the-art in unconventional biochemical computing and its applications.

Evgeny Katz received his Ph.D. in Chemistry from Frumkin Institute of Electrochemistry (Moscow) in 1983. He was a senior researcher in the Institute of Photosynthesis (Pushchino), Russian Academy of Sciences (1983-1991), a Humboldt fellow at Technische Universität München (Germany) (1992-1993), and a research associate professor at the Hebrew University of Jerusalem (1993-2006). Since 2006 he is Milton Kerker Chaired Professor at the Department of Chemistry and Biomolecular Science, Clarkson University, NY (USA). He has (co)authored over 300 papers in the areas of biocomputing, bioelectronics, biosensors and biofuel cells (Hirsch-index 65). Professor Katz serves as Editor-in-Chief for IEEE Sensors Journal and a member of editorial boards of many other journals.

Preface XIII

List of Contributors XV

1 Biomolecular Computing: From Unconventional Computing to ‘‘Smart’’ Biosensors and Actuators – Editorial Introduction 1
Evgeny Katz

References 5

2 Peptide-Based Computation: Switches, Gates, and Simple Arithmetic 9
Zehavit Dadon, Manickasundaram Samiappan, Nathaniel Wagner, Nurit Ashkenasy, and Gonen Ashkenasy

2.1 Introduction 9

2.2 Peptide-Based Replication Networks 10

2.3 Logic Gates within Ternary Networks 13

2.4 Symmetry and Order Requirements for Constructing the Logic Gates 16

2.5 Taking the Steps toward More Complex Arithmetic 19

2.6 Experimental Logic Gates 21

2.7 Adaptive Networks 24

2.8 Peptide-Based Switches and Gates for Molecular Electronics 28

2.9 Summary and Conclusion 29

Acknowledgments 30

References 30

3 Biomolecular Electronics and Protein-Based Optical Computing 33
Jordan A. Greco, Nicole L. Wagner, Matthew J. Ranaghan, Sanguthevar Rajasekaran, and Robert R. Birge

3.1 Introduction 33

3.2 Biomolecular and Semiconductor Electronics 34

3.3 Bacteriorhodopsin as a Photonic and Holographic Material for Bioelectronics 40

3.4 Fourier Transform Holographic Associative Processors 42

3.5 Three-Dimensional Optical Memories 45

3.6 Genetic Engineering of Bacteriorhodopsin for Device Applications 51

3.7 Future Directions 53

Acknowledgments 54

References 54

4 Bioelectronic Devices Controlled by Enzyme-Based Information Processing Systems 61
Evgeny Katz

4.1 Introduction 61

4.2 Enzyme-Based Logic Systems Producing pH Changes as Output Signals 62

4.3 Interfacing of the Enzyme Logic Systems with Electrodes Modified with Signal-Responsive Polymers 64

4.4 Switchable Biofuel Cells Controlled by the Enzyme Logic Systems 68

4.5 Biomolecular Logic Systems Composed of Biocatalytic and Biorecognition Units and Their Integration with Biofuel Cells 70

4.6 Processing of Injury Biomarkers by Enzyme Logic Systems Associated with Switchable Electrodes 74

4.7 Summary and Outlook 77

Acknowledgments 78

References 78

5 Enzyme Logic Digital Biosensors for Biomedical Applications 81
Evgeny Katz and Joseph Wang

5.1 Introduction 81

5.2 Enzyme-Based Logic Systems for Identification of Injury Conditions 82

5.3 Multiplexing of Injury Codes for the Parallel Operation of Enzyme Logic Gates 85

5.4 Scaling Up the Complexity of the Biocomputing Systems for Biomedical Applications – Mimicking Biochemical Pathways 89

5.5 Application of Filter Systems for Improving Digitalization of the Output Signals Generated by Enzyme Logic Systems for Injury Analysis 94

5.6 Conclusions and Perspectives 96

Acknowledgments 98

Appendix 98

References 99

6 Information Security Applications Based on Biomolecular Systems 103

Guinevere Strack, Heather R. Luckarift, Glenn R. Johnson, and Evgeny Katz

6.1 Introduction 103

6.2 Molecular and Bio-molecular Keypad Locks 104

6.3 Antibody Encryption and Steganography 108

6.4 Bio-barcode 113

6.5 Conclusion 114

Acknowledgments 114

References 114

7 Biocomputing: Explore Its Realization and Intelligent Logic Detection 117
Ming Zhou and Shaojun Dong

7.1 Introduction 117

7.2 DNA Biocomputing 119

7.3 Aptamer Biocomputing 121

7.4 Enzyme Biocomputing 124

7.5 Conclusions and Perspectives 128

References 129

8 Some Experiments and Models in Molecular Computing and Robotics 133
Milan N. Stojanovic and Darko Stefanovic

8.1 Introduction 133

8.2 From Gates to Programmable Automata 133

8.3 From Random Walker to Molecular Robotics 139

8.4 Conclusions 142

Acknowledgments 143

References 143

9 Biomolecular Finite Automata 145
Tamar Ratner, Sivan Shoshani, Ron Piran, and Ehud Keinan

9.1 Introduction 145

9.2 Biomolecular Finite Automata 146

9.3 Biomolecular Finite Transducer 167

9.4 Applications in Developmental Biology 172

9.5 Outlook 176

References 178

10 In Vivo Information Processing Using RNA Interference 181
Yaakov Benenson

10.1 Introduction 181

10.2 RNA Interference-Based Logic 183

10.3 Building the Sensory Module 189

10.4 Outlook 195

References 197

11 Biomolecular Computing Systems 199
Harish Chandran, Sudhanshu Garg, Nikhil Gopalkrishnan, and John H. Reif

11.1 Introduction 199

11.2 DNA as a Tool for Molecular Programming 200

11.3 Birth of DNA Computing: Adleman’s Experiment and Extensions 203

11.4 Computation Using DNA Tiles 205

11.5 Experimental Advances in Purely Hybridization-Based Computation 209

11.6 Experimental Advances in Enzyme-Based DNA Computing 212

11.7 Biochemical DNA Reaction Networks 217

11.8 Conclusion: Challenges in DNA-Based Biomolecular Computation 218

Acknowledgments 221

References 221

12 Enumeration Approach to the Analysis of Interacting Nucleic Acid Strands 225
Satoshi Kobayashi and Takaya Kawakami

12.1 Introduction 225

12.2 Definitions and Notations for Set and Multiset 226

12.3 Chemical Equilibrium and Hybridization Reaction System 227

12.4 Symmetric Enumeration Method 230

12.5 Applying SEM to Nucleic Acid Strands Interaction 236

12.6 Conclusions 243

References 244

13 Restriction Enzymes in Language Generation and Plasmid Computing 245
Tom Head

13.1 Introduction 245

13.2 Wet Splicing Systems 246

13.3 Dry Splicing Systems 249

13.4 Splicing Theory: Its Original Motivation and Its Extensive Unforeseen Developments 252

13.5 Computing with Plasmids 253

13.6 Fluid Memory 254

13.7 Examples of Aqueous Computations 255

13.8 Final Comments about Computing with Biomolecules 260

References 261

14 Development of Bacteria-Based Cellular Computing Circuits for Sensing and Control in Biological Systems 265
Michaela A. TerAvest, Zhongjian Li, and Largus T. Angenent

14.1 Introduction 265

14.2 Cellular Computing Circuits 267

14.3 Conclusion 276

Acknowledgments 277

References 277

15 The Logic of Decision Making in Environmental Bacteria 279
Rafael Silva-Rocha, Javier Tamames, and V´ıctor de Lorenzo

15.1 Introduction 279

15.2 Building Models for Biological Networks 281

15.3 Formulation and Simulation of Regulatory Networks 283

15.4 Boolean Analysis of Regulatory Networks 285

15.5 Boolean Description of m-xylene Biodegradation by P. putida mt-2: the TOL logicome 289

15.6 Conclusion and Outlook 298

Acknowledgments 299

References 299

16 Qualitative and Quantitative Aspects of a Model for Processes Inspired by the Functioning of the Living Cell 303
Andrzej Ehrenfeucht, Jetty Kleijn, Maciej Koutny, and Grzegorz Rozenberg

16.1 Introduction 303

16.2 Reactions 304

16.3 Reaction Systems 305

16.4 Examples 307

16.5 Reaction Systems with Measurements 310

16.6 Generalized Reactions 312

16.7 A Generic Quantitative Model 315

16.8 Approximations of Gene Expression Systems 316

16.9 Simulating Approximations by Reaction Systems 318

16.10 Discussion 319

Acknowledgments 321

References 321

17 Computational Methods for Quantitative Submodel Comparison 323
Andrzej Mizera, Elena Czeizler, and Ion Petre

17.1 Introduction 323

17.2 Methods for Model Decomposition 324

17.3 Methods for Submodel Comparison 327

17.4 Case Study 332

17.5 Discussion 342

Acknowledgments 343

References 343

18 Conclusions and Perspectives 347
Evgeny Katz

References 349

Index 351

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