| |
| |
Preface | |
| |
| |
Acknowledgements | |
| |
| |
| |
Global transitions in proteins | |
| |
| |
| |
Defining a global state | |
| |
| |
| |
Equilibrium between two global states | |
| |
| |
| |
Global transitions induced by temperature | |
| |
| |
| |
Lysozyme unfolding | |
| |
| |
| |
Steepness and enthalpy | |
| |
| |
| |
Cooperativity and thermal transitions | |
| |
| |
| |
Transitions induced by other variables | |
| |
| |
| |
Transitions induced by voltage | |
| |
| |
| |
The voltage sensor of voltage-gated channels | |
| |
| |
| |
Gating current | |
| |
| |
| |
Cooperativity and voltage-induced transitions | |
| |
| |
| |
Compliance of a global state | |
| |
| |
| |
Molecular forces in biological structures | |
| |
| |
| |
The Coulomb potential | |
| |
| |
| |
Electrostatic self-energy | |
| |
| |
| |
Image forces | |
| |
| |
| |
Charge-dipole interactions | |
| |
| |
| |
Induced dipoles | |
| |
| |
| |
Cation-[pi] interactions | |
| |
| |
| |
Dispersion forces | |
| |
| |
| |
Hydrophobic forces | |
| |
| |
| |
Hydration forces | |
| |
| |
| |
Hydrogen bonds | |
| |
| |
| |
Steric repulsions | |
| |
| |
| |
Bond flexing and harmonic potentials | |
| |
| |
| |
Stabilizing forces in proteins | |
| |
| |
| |
Protein force fields | |
| |
| |
| |
Stabilizing forces in nucleic acids | |
| |
| |
| |
Lipid bilayers and membrane proteins | |
| |
| |
| |
Conformations of macromolecules | |
| |
| |
| |
n-Butane | |
| |
| |
| |
Configurational partition functions and polymer chains | |
| |
| |
| |
Statistics of random coils | |
| |
| |
| |
Effective segment length | |
| |
| |
| |
Nonideal polymer chains and theta solvents | |
| |
| |
| |
Probability distributions | |
| |
| |
| |
Loop formation | |
| |
| |
| |
Stretching a random coil | |
| |
| |
| |
When do molecules act like random coils? | |
| |
| |
| |
Backbone rotations in proteins: secondary structure | |
| |
| |
| |
The entropy of protein denaturation | |
| |
| |
| |
The helix-coil transition | |
| |
| |
| |
Mathematical analysis of the helix-coil transition | |
| |
| |
| |
Results of helix-coil theory | |
| |
| |
| |
Helical propensities | |
| |
| |
| |
Protein folding | |
| |
| |
| |
Cooperativity in protein folding | |
| |
| |
| |
Molecular associations | |
| |
| |
| |
Association equilibrium in solution | |
| |
| |
| |
Cooperativity | |
| |
| |
| |
Concerted binding | |
| |
| |
| |
Sequential binding | |
| |
| |
| |
Nearest neighbor interactions | |
| |
| |
| |
Thermodynamics of associations | |
| |
| |
| |
Contact formation | |
| |
| |
| |
Statistical mechanics of association | |
| |
| |
| |
Translational free energy | |
| |
| |
| |
Rotational free energy | |
| |
| |
| |
Vibrational free energy | |
| |
| |
| |
Solvation effects | |
| |
| |
| |
Configurational free energy | |
| |
| |
| |
Protein association in membranes - reduction of dimensionality | |
| |
| |
| |
Binding to membranes | |
| |
| |
| |
Allosteric interactions | |
| |
| |
| |
The allosteric transition | |
| |
| |
| |
The simplest case: one binding site and one allosteric transition | |
| |
| |
| |
Binding and response | |
| |
| |
| |
Energy balance in the one-site model | |
| |
| |
| |
G-protein coupled receptors | |
| |
| |
| |
Binding site interactions | |
| |
| |
| |
The Monod-Wyman-Changeux (MWC) model | |
| |
| |
| |
Hemoglobin | |
| |
| |
| |
Energetics of the MWC model | |
| |
| |
| |
Macroscopic and microscopic additivity | |
| |
| |
| |
Phosphofructokinase | |
| |
| |
| |
Ligand-gated channels | |
| |
| |
| |
Subunit-subunit interactions: the Koshland-Nemethy-Filmer (KNF) model | |
| |
| |
| |
The Szabo-Karplus (SK) model | |
| |
| |
| |
Diffusion and Brownian motion | |
| |
| |
| |
Macroscopic diffusion: Fick's laws | |
| |
| |
| |
Solving the diffusion equation | |
| |
| |
| |
One-dimensional diffusion from a point | |
| |
| |
| |
Three-dimensional diffusion from a point | |
| |
| |
| |
Diffusion across an interface | |
| |
| |
| |
Diffusion with boundary conditions | |
| |
| |
| |
Diffusion at steady state | |
| |
| |
| |
A long pipe | |
| |
| |
| |
A small hole | |
| |
| |
| |
A porous membrane | |
| |
| |
| |
Microscopic diffusion - random walks | |
| |
| |
| |
Random walks and the Gaussian distribution | |
| |
| |
| |
The diffusion equation from microscopic theory | |
| |
| |
| |
Friction | |
| |
| |
| |
Stokes' law | |
| |
| |
| |
Diffusion constants of macromolecules | |
| |
| |
| |
Lateral diffusion in membranes | |
| |
| |
| |
Fundamental rate processes | |
| |
| |
| |
Exponential relaxations | |
| |
| |
| |
Activation energies | |
| |
| |
| |
The reaction coordinate and detailed balance | |
| |
| |
| |
Linear free energy relations | |
| |
| |
| |
Voltage-dependent rate constants | |
| |
| |
| |
The Marcus free energy relation | |
| |
| |
| |
Eyring theory | |
| |
| |
| |
Diffusion over a barrier - Kramers' theory | |
| |
| |
| |
Single-channel kinetics | |
| |
| |
| |
The reaction coordinate for a global transition | |
| |
| |
| |
Association kinetics | |
| |
| |
| |
Bimolecular association | |
| |
| |
| |
Small perturbations | |
| |
| |
| |
Diffusion-limited association | |
| |
| |
| |
Diffusion-limited dissociation | |
| |
| |
| |
Site binding | |
| |
| |
| |
Protein-ligand association rates | |
| |
| |
| |
Evolution of speed | |
| |
| |
| |
Acetylcholinesterase | |
| |
| |
| |
Horseradish peroxidase | |
| |
| |
| |
Proton transfer | |
| |
| |
| |
Binding to membrane receptors | |
| |
| |
| |
Reduction in dimensionality | |
| |
| |
| |
Binding to DNA | |
| |
| |
| |
Multi-state kinetics | |
| |
| |
| |
The three-state model | |
| |
| |
| |
Initial conditions | |
| |
| |
| |
Separation of timescales | |
| |
| |
| |
General solution to multi-state systems | |
| |
| |
| |
The three-state model in matrix notation | |
| |
| |
| |
Stationarity, conservation, and detailed balance | |
| |
| |
| |
Single-channel kinetics: the three-state model | |
| |
| |
| |
Separation of timescales in single channels: burst analysis | |
| |
| |
| |
General treatment of single-channel kinetics: state counting | |
| |
| |
| |
Relation between single-channel and macroscopic kinetics | |
| |
| |
| |
Loss of stationarity, conservation, and detailed balance | |
| |
| |
| |
Single-channel correlations: pathway counting | |
| |
| |
| |
Multisubunit kinetics | |
| |
| |
| |
Random walks and "stretched kinetics" | |
| |
| |
| |
Enzyme catalysis | |
| |
| |
| |
Basic mechanisms - serine proteases | |
| |
| |
| |
Michaelis-Menten kinetics | |
| |
| |
| |
Steady-state approximations | |
| |
| |
| |
Pre-steady-state kinetics | |
| |
| |
| |
Allosteric enzymes | |
| |
| |
| |
Utilization of binding energy | |
| |
| |
| |
Kramers' rate theory and catalysis | |
| |
| |
| |
Proximity and translational entropy | |
| |
| |
| |
Rotational entropy | |
| |
| |
| |
Reducing E[superscript dagger]: transition state complementarity | |
| |
| |
| |
Friction in an enzyme-substrate complex | |
| |
| |
| |
General-acid-base catalysis and Bronsted slopes | |
| |
| |
| |
Acid-base catalysis in [beta]-galactosidase | |
| |
| |
| |
Catalysis in serine proteases and strong H-bonds | |
| |
| |
| |
Marcus' theory and proton transfer in carbonic anhydrase | |
| |
| |
| |
Ions and counterions | |
| |
| |
| |
The Poisson-Boltzmann equation and the Debye length | |
| |
| |
| |
Activity coefficient of an ion | |
| |
| |
| |
Ionization of proteins | |
| |
| |
| |
Gouy-Chapman theory and membrane surface charge | |
| |
| |
| |
Stern's improvements of Gouy-Chapman theory | |
| |
| |
| |
Surface charge and channel conductance | |
| |
| |
| |
Surface charge and voltage gating | |
| |
| |
| |
Electrophoretic mobility | |
| |
| |
| |
Polyelectrolyte solutions I. Debye-Huckel screening | |
| |
| |
| |
Polyelectrolyte solutions II. Counterion-condensation | |
| |
| |
| |
DNA melting | |
| |
| |
| |
Fluctuations | |
| |
| |
| |
Deviations from the mean | |
| |
| |
| |
Number fluctuations and the Poisson distribution | |
| |
| |
| |
The statistics of light detection by the eye | |
| |
| |
| |
Equipartition of energy | |
| |
| |
| |
Energy fluctuations in a macromolecule | |
| |
| |
| |
Fluctuations in protein ionization | |
| |
| |
| |
Fluctuations in a two-state system | |
| |
| |
| |
Single-channel current | |
| |
| |
| |
The correlation function of a two-state system | |
| |
| |
| |
The Wiener-Khintchine theorem | |
| |
| |
| |
Channel noise | |
| |
| |
| |
Circuit noise | |
| |
| |
| |
Fluorescence correlation spectroscopy | |
| |
| |
| |
Friction and the fluctuation-dissipation theorem | |
| |
| |
| |
Ion permeation and membrane potential | |
| |
| |
| |
Nernst potentials | |
| |
| |
| |
Donnan potentials | |
| |
| |
| |
Membrane potentials of cells | |
| |
| |
| |
Neurons | |
| |
| |
| |
Vertebrate skeletal muscle | |
| |
| |
| |
A membrane permeable to Na[superscript +] and K[superscript +] | |
| |
| |
| |
Membrane potentials of neurons again | |
| |
| |
| |
The Ussing flux ratio and active transport | |
| |
| |
| |
The Goldman-Hodgkin-Katz voltage equation | |
| |
| |
| |
Membrane pumps and potentials | |
| |
| |
| |
Transporters and potentials | |
| |
| |
| |
The Goldman-Hodgkin-Katz current equation | |
| |
| |
| |
Divalent ions | |
| |
| |
| |
Surface charge and membrane potentials | |
| |
| |
| |
Rate theory and membrane potentials | |
| |
| |
| |
Ion permeation and channel structure | |
| |
| |
| |
Permeation without channels | |
| |
| |
| |
The Ohmic channel | |
| |
| |
| |
Energy barriers and channel properties | |
| |
| |
| |
Eisenman selectivity sequences | |
| |
| |
| |
Forces inside an ion channel | |
| |
| |
| |
Gramicidin A | |
| |
| |
| |
Rate theory for multibarrier channels | |
| |
| |
| |
Single-ion channels | |
| |
| |
| |
Single-file channels | |
| |
| |
| |
The KcsA channel | |
| |
| |
| |
Cable theory | |
| |
| |
| |
Current through membranes and cytoplasm | |
| |
| |
| |
The cable equation | |
| |
| |
| |
Steady state in a finite cable | |
| |
| |
| |
Voltage steps in a finite cable | |
| |
| |
| |
Current steps in a finite cable | |
| |
| |
| |
Branches and equivalent cylinder representations | |
| |
| |
| |
Steady state | |
| |
| |
| |
Time constants | |
| |
| |
| |
Cable analysis of a neuron | |
| |
| |
| |
Synaptic integration in dendrites: analytical models | |
| |
| |
| |
Impulse responses | |
| |
| |
| |
Realistic synaptic inputs | |
| |
| |
| |
Compartmental models and cable theory | |
| |
| |
| |
Synaptic integration in dendrites: compartmental models | |
| |
| |
| |
Action potentials | |
| |
| |
| |
The action potential | |
| |
| |
| |
The voltage clamp and the properties of Na[superscript +] and K[superscript +] channels | |
| |
| |
| |
The Hodgkin-Huxley equations | |
| |
| |
| |
Current-voltage curves and thresholds | |
| |
| |
| |
Propagation | |
| |
| |
| |
Myelin | |
| |
| |
| |
Axon geometry and conduction | |
| |
| |
| |
Channel diversity | |
| |
| |
| |
Repetitive activity and the A-current | |
| |
| |
| |
Oscillations | |
| |
| |
| |
Dendritic integration | |
| |
| |
| |
Expansions and series | |
| |
| |
| |
Taylor series | |
| |
| |
| |
The binomial expansion | |
| |
| |
| |
Geometric series | |
| |
| |
| |
Matrix algebra | |
| |
| |
| |
Linear transforms | |
| |
| |
| |
Determinants | |
| |
| |
| |
Eigenvalues, eigenvectors, and diagonalization | |
| |
| |
| |
Fourier analysis | |
| |
| |
| |
Gaussian integrals | |
| |
| |
| |
Hyperbolic functions | |
| |
| |
| |
Polar and spherical coordinates | |
| |
| |
References | |
| |
| |
Index | |