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Title: A classical dynamics study of the unbinding of ATP to the F1-ATPase
P9
Antes, Iris (1); Oster, George (2); Chandler, David (3)

antes@mpi-sb.mpg.de
(1) Max-Planck-Institut für Informatik, Saarbrücken, Germany, (2) Dep. of Molecular and Cellular Biology, University of California, Berkeley, USA, (3) Department of Chemistry, University of California, Berkeley, USA

F1-F0 ATP synthase is the world's smallest rotary motor. Coupled to an electrochemical proton gradient in its F0 transmembrane unit, the F1 unit synthesizes ATP from ADP and phosphate. The motor works with a very high efficiency and can reversibly hydrolyze or synthesize ATP.

Theoretical studies of the energy transduction in the F1 subunit by H. Wang and G. Oster showed that a sequential binding mechanism of the ATP molecule to its binding site is necessary for the motor to work with its high efficiency. This led to the proposition of the ``binding-zipper'' model [H. Wang and G. Oster, Nature, 396, 279 (1998)]. This model proposes that the hydrogen bonds, which are present between ATP and its binding pocket in the tight binding state, form progressively during the binding process, leading to a "zipper-like" binding mechanism.

We investigated the molecular mechanism of the unbinding of ATP in F1-ATPase from its tight binding state to its weak binding state. Our calculations are based on a set of atomic structures from Wang and Oster, which interpolate between the closed and open state of the binding pocket. We performed sixteen molecular dynamics simulations of the binding pocket region in the field of these interpolated atomic positions, which were used for the regions further away from the binding site. The forces from these distant atoms gradually drive the large primary region through a series of sixteen equilibrated steps tracing the rotation of the molecular motor and the opening of the binding pocket. As the rotation progresses, we find a sequential weakening and breaking of the hydrogen bonds between the ATP molecule and the ATPase. Our simulations confirm the ``binding zipper'' model and further suggest that the nucleotide's coordination with Mg2+ is a necessity for the high efficiency of the motor.