This book evolved from a graduate course on applications of statistical thermody­ namics to biochemical systems. Most of the published papers and books on this subject used in the course were written by experimentalists who adopted the phenomenological approach to describe and interpret their results. Two outstanding papers that impressed me deeply were the c1assical papers by Monod, Changeux, and Jacob (1963) and Monod, Wyman, and Changeux (1965), where the allosteric model for regulatory enzymes was introduced. Reading through them I feIt as if they were revealing one of the c1everest and most intricate tricks of nature to regulate biochemical processes. In 1985 I was glad to see T. L. HilI's volume entitled Cooperativity Theory in Biochemistry, Steady State and Equilibrium Systems. This was the fIrst book to systematically develop the molecular or statistical mechanical approach to binding systems. HilI demonstrated how and why the molecular approach is so advanta­ geous relative to the prevalent phenomenological approach of that time. On page 58 he wrote the following (my italics): The naturalness of Gibbs' grand partition function for binding problems in biology is evidenced by the rediscovery of what is essentially the grand partition function for this particular type of problem by various physical biochentists, including E. Q. Adams, G.

1. Introducing the Fundamental Concept. 2. The Binding Isotherm (BI). 3. Adsorption on a Single Polymer with Conformation Changes Induced by the Binding Process. 4. Two-site Systems; Direct and Indirect Cooperativity. 5. Three-site Systems; Non-additivity and Long Range Correlations. 6. 7. Large Linear Systems of Binding Sites. 8. Regulatory Enzymes. 9. Solvent Effects on Cooperativity. 10. Appendices. Appendix A: Pair and triple correlations between events. Appendix B: Localization of the adsorbent molecules, and its effect on the binding isotherm. Appendix C: Transition from microstates to macrostates. Appendix D: First order correction to non-ideality of the ligand''s reservoir. Appendix E: Relative slopes of the equilibrated and "frozen in" BI''s in a multi macrostate system. Appendix F: Spurious cooperativity in single-site systems. Appendix G: The relation between the binding isotherm and the titration curves for two-site systems. Appendix H: Synthetic data. Appendix I: A comment on nomenclature. Appendix J: Average binding constants and correlation functions. Appendix K: Utility function in binding systems.