Theory of Single Molecule Experiments of F_1-ATpase: Predictions, Tests and Comparison with Experiments

Abstract

There is now a substantial body of single molecule experiments on biomolecular motors, supplementing the extensive structural and ensemble data on these systems. Our current focus is on the motor, F_1-ATPase, a component of the enzyme ATP Synthase that uses proton gradients to synthesize ATP. Our interest is in seeing what information single molecule studies may provide on the relation between structural changes and the rates of various processes involved in the ATP binding, release, hydrolysis and synthesis. Our approach is to utilize a class of kinetic-thermodynamic relations used for chemical reactions and originally coming from the field of electron and other transfer reactions. To adapt those relations to biomolecular motors we incorporated into the kinetic-thermodynamic free energy expressions an elastic interaction between the rotor and stator subunits of the motor, and coupled the rotor to the chemical and physical processes. The theory is aimed at adding insights to the different of rates in terms of protein structure. On the more technical side another aim is to relate one type of single molecule experiment to another and to ensemble experiments. Theory-based predictions are made and compared with experiment. Some of our recent PNAS studies are summarized, together with more recent results.