Entropy-enthalpy Compensation Conformational Fluctuation and Induced--t

A localized change in a protein, which occurs as a result of either ligand binding or single amino acid substitution, necessarily encounters the conformational uctuation of the rest of the protein. Both the entropy and the enthalpy associated with the change consist of contributions from uctuations in the atoms surrounding the localized site, but they compensate. A novel thermodynamic ensemble with a uctuating boundary is proposed for studying the energetics of localized changes in proteins. Using an ideal gas as illustration, it is shown that the entropy-enthalpy compensation re ects the exibility of the surrounding structures Its uctuations contribute a term to the entropy and the conformational change associated with the inducedt contributes a term to the enthalpy. INTRODUCTION Entropy-enthalpy compensation is a widely observed phenomenon in biochemistry. A recent thermodynamic analysis has shown that the compensation phenomenon is intimately related to the types of constraints on the boundary of a thermodynamic system, and there is a unifying physical origin of this phenomenon in various molecular systems. In the same study, it was also suggested that uctuations of the boundary of a molecular system contribute to the system's partial molar entropy and enthalpy, but in such a way that they compensate. This note provides a simple derivation of this conjecture by introducing a novel uctuating boundary ensemble, and using a system of an ideal gas as an illustration. A thermodynamic framework is proposed for the interpretation of energetic measurements on protein-ligand interactions and changes in protein stability upon site-directed mutagenesis. A general statistical mechanical derivation can be carried out similarly. It would involve more cumbersome algebra but would not provide further physical insight. Hence, for this presentation, we simply use the ideal gas for illustrating the basic idea rather then presenting the general derivation. IDEAL GAS SYSTEM WITH FLUCTUATING BOUNDARY