Preface |
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xiii | |
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PART I THE MAKING OF MOLECULAR SWITCHES |
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1 | (74) |
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1 It's An Allosteric World |
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3 | (32) |
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1.1 The Second Secret of Life |
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3 | (1) |
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1.2 The Broad Reach of the Allostery Concept |
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4 | (10) |
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1.2.1 Sculpting Biochemistry via Allostery |
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5 | (4) |
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1.2.2 One- and Two-Component Signal Transduction and the Two-State Philosophy |
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9 | (5) |
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1.3 Reasoning about Feedback: The Rise of Allostery |
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14 | (6) |
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14 | (3) |
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1.3.2 The Resolution of the Molecular Feedback Puzzle |
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17 | (3) |
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1.3.3 Finding the Allosterome |
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20 | (1) |
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1.4 Mathematicizing the Two-State Paradigm |
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20 | (8) |
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1.4.1 Transcendent Concepts in Physics |
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22 | (3) |
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1.4.2 One Equation to Rule Them All |
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25 | (3) |
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1.5 Beyond the MWC Two-State Concept |
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28 | (2) |
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1.5.1 Molecular Agnosticism: MWC versus KNF versus Eigen |
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28 | (2) |
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30 | (1) |
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31 | (1) |
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32 | (1) |
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33 | (2) |
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2 The Allosterician's Toolkit |
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35 | (40) |
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2.1 A Mathematical Microscope: Statistical Mechanics Preliminaries |
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35 | (9) |
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36 | (2) |
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2.1.2 The Fundamental Law of Statistical Mechanics |
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38 | (2) |
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2.1.3 The Dimensionless Numbers of Thermal Physics |
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40 | (4) |
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2.1.4 Boltzmann and Probabilities |
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44 | (1) |
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2.2 Case Study in Statistical Mechanics: Ligand-Receptor Binding |
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44 | (5) |
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2.2.1 Ligand Binding and the Lattice Model of Solutions |
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45 | (4) |
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2.3 Conceptual Tools of the Trade: Free Energy and Entropy |
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49 | (5) |
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2.3.1 Resetting Our Zero of Energy Using the Chemical Potential |
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51 | (3) |
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2.4 The MWC Concept in Statistical Mechanical Language |
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54 | (3) |
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2.5 Cooperativity and Allostery |
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57 | (6) |
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2.5.1 Cooperativity and Hill Functions |
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59 | (2) |
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2.5.2 Cooperativity in the MWC Model |
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61 | (2) |
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2.6 Internal Degrees of Freedom and Ensemble Allostery |
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63 | (7) |
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70 | (3) |
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73 | (1) |
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73 | (1) |
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74 | (1) |
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PART II THE LONG REACH OF ALLOSTERY |
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75 | (270) |
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3 Signaling At The Cell Membrane: Ion Channels |
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77 | (47) |
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3.1 How Cells Talk to the World |
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77 | (1) |
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3.2 Biological Processes and Ion Channels |
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78 | (3) |
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3.3 Ligand-Gated Channels |
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81 | (3) |
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3.4 Statistical Mechanics of the MWC Channel |
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84 | (10) |
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3.5 Data Collapse, Natural Variables, and the Bohr Effect |
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94 | (4) |
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3.5.1 Data Collapse and the Ion-Channel Bohr Effect |
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95 | (3) |
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3.6 Rate Equation Description of Channel Gating |
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98 | (8) |
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3.7 Cyclic Nucleotide--Gated Channels |
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106 | (6) |
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3.8 Beyond the MWC Model in Ion Channelology |
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112 | (9) |
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3.8.1 Conductance Substates and Conformational Kinetics |
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113 | (2) |
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3.8.2 The Koshland-Nemethy-Filmer Model Revealed |
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115 | (3) |
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3.8.3 Kinetic Proliferation |
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118 | (2) |
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3.8.4 The Question of Inactivation |
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120 | (1) |
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121 | (1) |
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121 | (1) |
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122 | (2) |
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4 How Bacteria Navigate The World Around Them |
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124 | (46) |
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4.1 Bacterial Information Processing |
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124 | (3) |
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4.1.1 Engelmanns Experiment and Bacterial Aerotaxis |
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124 | (1) |
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4.1.2 Love Thy Neighbors: Signaling between Bacteria |
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125 | (2) |
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127 | (8) |
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4.2.1 The Chemotaxis Phenomenon |
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127 | (2) |
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4.2.2 Wiring Up Chemotaxis through Molecular Switching |
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129 | (6) |
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4.3 MWC Models of Chemotactic Response |
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135 | (11) |
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4.3.1 MWC Model of Chemotaxis Receptor Clusters |
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139 | (4) |
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4.3.2 Heterogenous Clustering |
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143 | (2) |
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4.3.3 Putting It All Together by Averaging |
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145 | (1) |
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4.4 The Amazing Phenomenon of Physiological Adaptation |
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146 | (9) |
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151 | (2) |
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4.4.2 Data Collapse in Chemotaxis |
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153 | (2) |
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4.5 Beyond the MWC Model in Bacterial Chemotaxis |
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155 | (1) |
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4.5 The Ecology and Physiology of Quorum Sensing |
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156 | (10) |
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4.6.1 Wiring Up Quorum Sensing |
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158 | (2) |
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4.6.2 Dose-Response Curves in Quorum Sensing |
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160 | (2) |
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4.6.3 Statistical Mechanics of Membrane Receptors |
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162 | (2) |
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4.6.4 Statistical Mechanics of Membrane Receptors with Inhibitors |
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164 | (1) |
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4.6.5 Data Collapse in Quorum Sensing |
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165 | (1) |
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166 | (1) |
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4.8 Further Reading and Viewing |
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166 | (2) |
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168 | (2) |
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5 The Wonderful World Of G Proteins And G Protein--Coupled Receptors |
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170 | (31) |
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171 | (6) |
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5.1.1 Crypsis in Field Mice |
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171 | (2) |
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5.1.2 Coat Color and GPCRs |
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173 | (4) |
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5.2 The G Protein-Coupled Receptor Paradigm |
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177 | (1) |
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5.3 Paradigmatic Examples of GPCRs |
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177 | (15) |
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5.3.1 The β-Adrenergic Receptor |
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179 | (4) |
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5.3.2 Vision, Rhodopsin, and Signal Transduction |
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183 | (4) |
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5.3.3 Light as a Ligand: Optogenetics |
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187 | (5) |
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5.4 G Protein--Coupled Ion Channels |
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192 | (6) |
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198 | (1) |
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5.6 Further Reading and Viewing |
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198 | (1) |
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199 | (2) |
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6 Dynamics Of Mwc Molecules: Enzyme Action And Allostery |
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201 | (30) |
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201 | (4) |
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6.2 Statistical Mechanics of Michaelis-Menten Enzymes |
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205 | (4) |
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6.3 Statistical Mechanics of MWC Enzymes |
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209 | (13) |
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6.3.1 Modulating Enzyme Activity with Allosteric Effectors |
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213 | (4) |
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6.3.2 Competitive Inhibitors and Enzyme Action |
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217 | (3) |
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6.3.3 Multiple Substrate Binding Sites |
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220 | (1) |
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221 | (1) |
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6.4 Glycolysis and Allostery |
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222 | (6) |
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6.4.1 The Case of Phosphofructokinase |
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223 | (5) |
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228 | (1) |
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229 | (1) |
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230 | (1) |
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7 Hemoglobin, Nature's Honorary Enzyme |
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231 | (41) |
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7.1 Hemoglobin Claims Its Place in Science |
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231 | (8) |
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7.1.1 Hemoglobin and Respiration |
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232 | (3) |
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7.1.2 A Historical Interlude on the Colouring Matter |
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235 | (1) |
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7.1.3 Hemoglobin as a "Document of Evolutionary History" |
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236 | (3) |
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7.2 States and Weights and Binding Curves |
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239 | (5) |
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244 | (2) |
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7.4 Hemoglobin and Effectors: The Bohr Effect and Beyond |
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246 | (6) |
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7.5 Physiological versus Evolutionary Adaptation: High Fliers and Deep Divers |
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252 | (7) |
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7.6 Hemoglobin and Competitors: Carbon Monoxide Fights Oxygen |
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259 | (5) |
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7.7 Pushing the MWC Framework Harder: Hemoglobin Kinetics |
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264 | (4) |
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268 | (1) |
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269 | (1) |
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270 | (2) |
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8 How Cells Decide What To Be: Signaling And Gene Regulation |
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272 | (31) |
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8.1 Of Repressors, Activators, and Allostery |
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273 | (4) |
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8.2 Thermodynamic Models of Gene Expression |
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277 | (7) |
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284 | (6) |
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290 | (9) |
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8.4.1 Binding of Inducer to Activator |
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291 | (3) |
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8.4.2 Binding of Activator to DNA |
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294 | (3) |
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8.4.3 Activation and Gene Expression |
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297 | (2) |
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299 | (1) |
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300 | (1) |
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301 | (1) |
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302 | (1) |
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9 Building Logic From Allostery |
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303 | (13) |
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9.1 Combinatorial Control and Logic Gates |
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303 | (3) |
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9.2 Using MWC to Build Gates |
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306 | (5) |
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307 | (2) |
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9.2.2 A Tour of Parameter Space |
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309 | (2) |
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9.3 Beyond Two-Input Logic |
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311 | (3) |
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314 | (1) |
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315 | (1) |
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10 Dna Packing And Access: The Physics Of Combinatorial Control |
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316 | (29) |
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10.1 Genome Packing and Accessibility |
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316 | (2) |
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10.2 The Paradox of Combinatorial Control and Genomic Action at a Distance |
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318 | (2) |
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10.3 Nucleosomes and DNA Accessibility |
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320 | (10) |
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10.3.1 Equilibrium Accessibility of Nucleosomal DNA |
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324 | (6) |
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10.4 MWC Model of Nucleosomes: Arbitrary Number of Binding Sites |
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330 | (4) |
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10.5 Nucleosome Modifications and the Analogy with the Bohr Effect |
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334 | (2) |
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10.6 Stepping Up in Scales: A Toy Model of Combinatorial Control at Enhancers |
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336 | (4) |
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10.7 An Application of the MWC Model of Nucleosomes to Embryonic Development |
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340 | (2) |
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342 | (1) |
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343 | (1) |
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343 | (2) |
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PART III BEYOND ALLOSTERY |
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345 | (64) |
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347 | (18) |
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347 | (8) |
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11.1.1 Normal Modes and Mechanisms of Action at a Distance |
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349 | (2) |
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11.1.2 Integrating Out Degrees of Freedom |
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351 | (4) |
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11.2 Ensemble Allostery through Tethering |
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355 | (6) |
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11.2.1 Biochemistry on a Leash |
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355 | (2) |
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11.2.2 Random-Walk Models of Tethers |
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357 | (4) |
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11.3 Irreversible Allostery |
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361 | (1) |
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362 | (2) |
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364 | (1) |
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364 | (1) |
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12 Maxwell Demons, Proofreading, And Allostery |
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365 | (30) |
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365 | (1) |
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12.2 A Panoply of Demonic Behaviors in the Living World |
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366 | (17) |
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12.2.1 The Demon and Biological Specificity |
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368 | (5) |
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12.2.2 Making Stuff Happen in the Right Order |
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373 | (3) |
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12.2.3 The Free-Energy Cost of Demonic Behavior |
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376 | (7) |
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12.3 Overcoming Thermodynamics in Biology: Kinetic Proofreading |
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383 | (9) |
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12.3.1 Equilibrium Discrimination Is Not Enough |
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383 | (2) |
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12.3.2 The Hopfield-Ninio Mechanism |
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385 | (1) |
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12.3.3 Proofreading Goes Steampunk: Building Proofreading Engines |
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386 | (6) |
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392 | (1) |
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392 | (1) |
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393 | (2) |
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13 A Farewell To Allostery |
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395 | (14) |
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13.1 Diversity and Unity: Diverging and Converging Views of Biology |
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396 | (5) |
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13.2 Shortcomings of the Approach |
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401 | (4) |
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405 | (1) |
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406 | (1) |
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407 | (2) |
Index |
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409 | |