PrefaceI. Introduction References II. Thermodynamics and Model Systems I. Introduction II. Some Concepts in Thermodynamics III. Multiple Binding without Interaction between Sites IV. Binding with Interaction between Sites A. Debye-Hückel-Born Treatment of Electrostatic Interaction B. Tanford-Kirkwood Model for Electrostatic Interaction C. Hill Model for Cylindrical Rods V. Method of Data Treatment VI. Thermodynamics of Multiple Equilibria VII. Binding-Induced Phase Transitions VIII. Linked Functions References III. The Measurement of Complex Formation I. Introduction II. Subtractive Methods A. EMF Measurements of Free Ligand Activity B. Equilibrium Dialysis C. Ultrafiltration and Ultracentrifugation D. Gel Filtration E. Partition Equilibrium between Phases F. Electrical Conductivity G. Polarography H. Determination of Free Ligand without Separation of Phases III. Direct Measurements A. Changes in Light Absorption of Ligand B. Fluorescence Methods C. Optical Rotation D. Nuclear Magnetic Resonance E. X-Ray Diffraction F. Refractive Index G. Light-Scattering and Osmotic Pressure H. Biological Activity IV. Electrostatic Methods A. Electrophoresis B. Changes in the Titration Curves of Proteins due to the Presence of Bound Ions C. The pH Method of Scatchard and Black—Displacement of pH of Isoionic Solutions by Added Salt D. Dielectric Increment and Dispersion V. Other Methods A. Complement Fixation B. Methods which Depend on Competition References IV. Binding of Neutral Molecules I. Introduction II. Results Obtained with Particular Proteins A. Serum Albumins B. β-Lactoglobulin C. Myoglobin and Hemoglobin D. Lysozyme E. Other Enzymes F. Globulins G. α-Acid Glycoprotein (Human) H. Concanavalin A I. Myosin III. The Hydration of Proteins A. The State of Combined Water IV. Interactions with Other Solvents A. Dependence on High Powers of Concentration V. Mechanism of Binding of Neutral Molecules References V. Hydrogen-Ion Equilibria I. Introduction II. Prototropic Groups in Proteins III. Some Experimental Details A. Isoionic Point B. Definition of pH IV. An Experimental Titration Curve V. Anomalies Illustrated by Specific Proteins A. Bovine Serum Albumin—Abnormal Carboxylate Groups B. ß-Lactoglobulin—Abnormal Carboxyl and Thiol Groups C. Ribonuclease—Abnormal Phenolic Groups D. Hemoglobin—Abnormal Imidazole Groups E. Insulin and Zinc Insulin F. Paramyosin, a Rodlike Protein VI. Hydrogen-Ion Equilibria of Denatured Proteins VII. Unfolding as a Function of Protonation A. Bovine Serum Albumin B. E. coli Alkaline Phosphatase VIII. Summary References VI. Metal-Ion Binding I. Metal Ions and Their Complexes in Solution II. Experimental Methods and Data Treatment III. Proteins Containing Metal Ions Necessary for Biological Activity IV. Protein-Metal Complex Formation A. Bovine Serum Albumin B. Sperm Whale Myoglobin C. Ribonuclease D. Vasopressin and Oxytocin E. Insulin F. Membranes G. Ribosomes H. S-100, a Protein of the Nervous System References VII. Binding of Organic Ions by Proteins I. Introduction II. Large Organic Ions—Ionic Detergents A. Early Work on Detergent Anions B. Isotherms of Anionic Detergents C. The Binding of Fatty Acids Compared to Other Ligands. Nature of the Binding Site D. Criteria of Unfolding. Viscosity Deuterium Exchange, ORD, and Difference Spectra E. Effects of pH on Anion Binding F. Other Effects of Detergents on Proteins G. Enthalpy Change in Binding. Uniqueness of Two Highest Energy Sites of BSA H. Binding of Polyions III. Dyes, Dye-Like, and Other Cyclic Molecules Binding as Ions A. Early Work B. The Affinities of Some Dyes to Proteins C. Fluorescent Ligands D. Dye Interactions with Denatured Protein E. Protection by Dyes against Denaturation F. Phytic Acid IV. Binding of Small Nonaromatic Ions to Proteins A. Early Work B. Thermodynamic Studies (Affinities and Numbers of Sites) C. Supporting Data and Applications D. Additional Data E. Cations F. Evidence from Electrophoresis G. Evidence from Conformational Effects H. Protection against Unfolding I. Miscellaneous Reports of Small Ion Binding to Proteins J. Kinetics of Binding Processes K. Effect of Binding on Subunit Interactions References VIII. Protein-Protein Interaction I. Introduction II. Quarternary Structure in Proteins III. Glutamic Dehydrogenase IV. Tobacco Mosaic Virus Protein V. Hemerythrin References IX. Summary and Conclusions References Author IndexSubject Index