PH.D Student

Abstract

Manipulations that alter the energetics of a chemical reaction often alter the activation free energy in linear correlation with the equilibrium free energy change. Such linear free energy relationship (LFERs) have been widely used to probe the energetics of transition states associated with protein folding and enzymatic catalysis. Nevertheless, the physical basis that underlie LFERs in such systems are not well understood, and it is not obvious how the slope of the linear relation should be interpreted. We show that the effects of amphiphiles on gramicidin A(gA) channel gating in lipid bilayers obeys a LFER and have studied the underlying mechanisms. The channel gating process provides a unique chemical reaction, in which structural changes in a model protein can be studied at the level of single molecules, while offering quantitative information about the energetics of a reaction transition state and its position on a spatial coordinate. We show that the LFER can be understood - and that the slope of the linear relation between changes in activation energy and equilibrium free energy for channel formation can be interpreted - by considering the effects of amphiphiles on the changes in bilayer elastic energy associated with channel gating. The use of amphiphile-induced changes in bilayer elastic properties provide a tool for studying LFERs associated with membrane protein function and folding.