Molecular and Cellular Biophysics

By: Meyer B. Jackson

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Paperback | 24 January 2006

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528 Pages

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Molecular and Cellular Biophysics provides advanced undergraduate and graduate students with a foundation in the basic concepts of biophysics. Students who have taken physical chemistry and calculus courses will find this book an accessible and valuable aid in learning how these concepts can be used in biological research. The text provides a rigorous treatment of the fundamental theories in biophysics and illustrates their application with examples. Conformational transitions of proteins are studied first using thermodynamics, and subsequently with kinetics. Allosteric theory is developed as the synthesis of conformational transitions and association reactions. Basic ideas of thermodynamics and kinetics are applied to topics such as protein folding, enzyme catalysis and ion channel permeation. These concepts are then used as the building blocks in a treatment of membrane excitability. Through these examples, students will gain an understanding of the general importance and broad applicability of biophysical principles to biological problems.

Industry Reviews

'...would be a valuable addition to the library of any research lab at the physical end of biochemistry. ... The language used in the book is extremely clear, and a mathematical approach is combined with clear links to real biochemistry ...' Chemistry world

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Non-Fiction Medicine Pre-Clinical Medicine & Basic Sciences Physiology Science Biology, Life Sciences Molecular Biology Physics Applied Physics Biophysics Cellular Biology

Preface	p. xii
Acknowledgements	p. xiv
Global transitions in proteins	p. 1
Defining a global state	p. 2
Equilibrium between two global states	p. 4
Global transitions induced by temperature	p. 5
Lysozyme unfolding	p. 7
Steepness and enthalpy	p. 9
Cooperativity and thermal transitions	p. 11
Transitions induced by other variables	p. 12
Transitions induced by voltage	p. 14
The voltage sensor of voltage-gated channels	p. 17
Gating current	p. 18
Cooperativity and voltage-induced transitions	p. 19
Compliance of a global state	p. 21
Molecular forces in biological structures	p. 25
The Coulomb potential	p. 25
Electrostatic self-energy	p. 27
Image forces	p. 29
Charge-dipole interactions	p. 31
Induced dipoles	p. 32
Cation-[pi] interactions	p. 33
Dispersion forces	p. 35
Hydrophobic forces	p. 36
Hydration forces	p. 39
Hydrogen bonds	p. 39
Steric repulsions	p. 43
Bond flexing and harmonic potentials	p. 44
Stabilizing forces in proteins	p. 46
Protein force fields	p. 50
Stabilizing forces in nucleic acids	p. 52
Lipid bilayers and membrane proteins	p. 53
Conformations of macromolecules	p. 56
n-Butane	p. 56
Configurational partition functions and polymer chains	p. 58
Statistics of random coils	p. 60
Effective segment length	p. 62
Nonideal polymer chains and theta solvents	p. 63
Probability distributions	p. 65
Loop formation	p. 66
Stretching a random coil	p. 67
When do molecules act like random coils?	p. 68
Backbone rotations in proteins: secondary structure	p. 68
The entropy of protein denaturation	p. 71
The helix-coil transition	p. 73
Mathematical analysis of the helix-coil transition	p. 74
Results of helix-coil theory	p. 78
Helical propensities	p. 80
Protein folding	p. 82
Cooperativity in protein folding	p. 86
Molecular associations	p. 89
Association equilibrium in solution	p. 89
Cooperativity	p. 91
Concerted binding	p. 91
Sequential binding	p. 93
Nearest neighbor interactions	p. 94
Thermodynamics of associations	p. 94
Contact formation	p. 95
Statistical mechanics of association	p. 96
Translational free energy	p. 98
Rotational free energy	p. 101
Vibrational free energy	p. 102
Solvation effects	p. 105
Configurational free energy	p. 106
Protein association in membranes - reduction of dimensionality	p. 107
Binding to membranes	p. 108
Allosteric interactions	p. 111
The allosteric transition	p. 112
The simplest case: one binding site and one allosteric transition	p. 112
Binding and response	p. 115
Energy balance in the one-site model	p. 116
G-protein coupled receptors	p. 117
Binding site interactions	p. 121
The Monod-Wyman-Changeux (MWC) model	p. 123
Hemoglobin	p. 126
Energetics of the MWC model	p. 127
Macroscopic and microscopic additivity	p. 128
Phosphofructokinase	p. 130
Ligand-gated channels	p. 132
Subunit-subunit interactions: the Koshland-Nemethy-Filmer (KNF) model	p. 134
The Szabo-Karplus (SK) model	p. 137
Diffusion and Brownian motion	p. 142
Macroscopic diffusion: Fick's laws	p. 142
Solving the diffusion equation	p. 143
One-dimensional diffusion from a point	p. 144
Three-dimensional diffusion from a point	p. 146
Diffusion across an interface	p. 146
Diffusion with boundary conditions	p. 148
Diffusion at steady state	p. 150
A long pipe	p. 151
A small hole	p. 152
A porous membrane	p. 153
Microscopic diffusion - random walks	p. 154
Random walks and the Gaussian distribution	p. 156
The diffusion equation from microscopic theory	p. 159
Friction	p. 160
Stokes' law	p. 162
Diffusion constants of macromolecules	p. 163
Lateral diffusion in membranes	p. 164
Fundamental rate processes	p. 167
Exponential relaxations	p. 167
Activation energies	p. 169
The reaction coordinate and detailed balance	p. 170
Linear free energy relations	p. 172
Voltage-dependent rate constants	p. 175
The Marcus free energy relation	p. 177
Eyring theory	p. 179
Diffusion over a barrier - Kramers' theory	p. 180
Single-channel kinetics	p. 183
The reaction coordinate for a global transition	p. 186
Association kinetics	p. 194
Bimolecular association	p. 194
Small perturbations	p. 195
Diffusion-limited association	p. 197
Diffusion-limited dissociation	p. 200
Site binding	p. 201
Protein-ligand association rates	p. 203
Evolution of speed	p. 205
Acetylcholinesterase	p. 205
Horseradish peroxidase	p. 206
Proton transfer	p. 207
Binding to membrane receptors	p. 208
Reduction in dimensionality	p. 212
Binding to DNA	p. 214
Multi-state kinetics	p. 216
The three-state model	p. 216
Initial conditions	p. 219
Separation of timescales	p. 220
General solution to multi-state systems	p. 221
The three-state model in matrix notation	p. 225
Stationarity, conservation, and detailed balance	p. 226
Single-channel kinetics: the three-state model	p. 229
Separation of timescales in single channels: burst analysis	p. 232
General treatment of single-channel kinetics: state counting	p. 235
Relation between single-channel and macroscopic kinetics	p. 236
Loss of stationarity, conservation, and detailed balance	p. 237
Single-channel correlations: pathway counting	p. 240
Multisubunit kinetics	p. 242
Random walks and "stretched kinetics"	p. 244
Enzyme catalysis	p. 248
Basic mechanisms - serine proteases	p. 248
Michaelis-Menten kinetics	p. 251
Steady-state approximations	p. 254
Pre-steady-state kinetics	p. 256
Allosteric enzymes	p. 257
Utilization of binding energy	p. 258
Kramers' rate theory and catalysis	p. 259
Proximity and translational entropy	p. 260
Rotational entropy	p. 263
Reducing E[superscript dagger]: transition state complementarity	p. 264
Friction in an enzyme-substrate complex	p. 267
General-acid-base catalysis and Bronsted slopes	p. 268
Acid-base catalysis in [beta]-galactosidase	p. 270
Catalysis in serine proteases and strong H-bonds	p. 272
Marcus' theory and proton transfer in carbonic anhydrase	p. 273
Ions and counterions	p. 276
The Poisson-Boltzmann equation and the Debye length	p. 277
Activity coefficient of an ion	p. 279
Ionization of proteins	p. 283
Gouy-Chapman theory and membrane surface charge	p. 285
Stern's improvements of Gouy-Chapman theory	p. 288
Surface charge and channel conductance	p. 291
Surface charge and voltage gating	p. 293
Electrophoretic mobility	p. 294
Polyelectrolyte solutions I. Debye-Huckel screening	p. 297
Polyelectrolyte solutions II. Counterion-condensation	p. 300
DNA melting	p. 302
Fluctuations	p. 307
Deviations from the mean	p. 307
Number fluctuations and the Poisson distribution	p. 309
The statistics of light detection by the eye	p. 311
Equipartition of energy	p. 313
Energy fluctuations in a macromolecule	p. 315
Fluctuations in protein ionization	p. 317
Fluctuations in a two-state system	p. 319
Single-channel current	p. 320
The correlation function of a two-state system	p. 322
The Wiener-Khintchine theorem	p. 324
Channel noise	p. 327
Circuit noise	p. 329
Fluorescence correlation spectroscopy	p. 332
Friction and the fluctuation-dissipation theorem	p. 336
Ion permeation and membrane potential	p. 339
Nernst potentials	p. 339
Donnan potentials	p. 341
Membrane potentials of cells	p. 343
Neurons	p. 345
Vertebrate skeletal muscle	p. 345
A membrane permeable to Na[superscript +] and K[superscript +]	p. 347
Membrane potentials of neurons again	p. 350
The Ussing flux ratio and active transport	p. 351
The Goldman-Hodgkin-Katz voltage equation	p. 352
Membrane pumps and potentials	p. 354
Transporters and potentials	p. 355
The Goldman-Hodgkin-Katz current equation	p. 357
Divalent ions	p. 360
Surface charge and membrane potentials	p. 361
Rate theory and membrane potentials	p. 362
Ion permeation and channel structure	p. 367
Permeation without channels	p. 367
The Ohmic channel	p. 370
Energy barriers and channel properties	p. 371
Eisenman selectivity sequences	p. 374
Forces inside an ion channel	p. 376
Gramicidin A	p. 378
Rate theory for multibarrier channels	p. 380
Single-ion channels	p. 384
Single-file channels	p. 390
The KcsA channel	p. 394
Cable theory	p. 400
Current through membranes and cytoplasm	p. 401
The cable equation	p. 403
Steady state in a finite cable	p. 406
Voltage steps in a finite cable	p. 408
Current steps in a finite cable	p. 411
Branches and equivalent cylinder representations	p. 412
Steady state	p. 413
Time constants	p. 415
Cable analysis of a neuron	p. 418
Synaptic integration in dendrites: analytical models	p. 422
Impulse responses	p. 423
Realistic synaptic inputs	p. 425
Compartmental models and cable theory	p. 428
Synaptic integration in dendrites: compartmental models	p. 430
Action potentials	p. 434
The action potential	p. 434
The voltage clamp and the properties of Na[superscript +] and K[superscript +] channels	p. 439
The Hodgkin-Huxley equations	p. 442
Current-voltage curves and thresholds	p. 447
Propagation	p. 450
Myelin	p. 453
Axon geometry and conduction	p. 455
Channel diversity	p. 457
Repetitive activity and the A-current	p. 458
Oscillations	p. 461
Dendritic integration	p. 466
Expansions and series	p. 470
Taylor series	p. 470
The binomial expansion	p. 471
Geometric series	p. 471
Matrix algebra	p. 472
Linear transforms	p. 472
Determinants	p. 473
Eigenvalues, eigenvectors, and diagonalization	p. 474
Fourier analysis	p. 477
Gaussian integrals	p. 481
Hyperbolic functions	p. 483
Polar and spherical coordinates	p. 484
References	p. 486
Index	p. 504
Table of Contents provided by Ingram. All Rights Reserved.

Molecular and Cellular Biophysics

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