Structural fluctuation and concerted motions in F(1)-ATPase: A molecular dynamics study

F(1)-ATPase is an adenosine tri-phosphate (ATP)-driven rotary motor enzyme. We investigated the structural fluctuations and concerted motions of subunits in F(1)-ATPase using molecular dynamics (MD) simulations. An MD simulation for the alpha(3)beta(3)gamma complex was carried out for 30 ns. Although large fluctuations of the N-terminal domain observed in simulations of the isolated beta(E) subunit were suppressed in the complex simulation, the magnitude of fluctuations in the C-terminal domain was clearly different among the three beta subunits (beta(E), beta(TP), and beta(DP)). Despite fairly similar conformations of the beta(TP) and beta(DP) subunits, the beta(DP) subunit exhibits smaller fluctuations in the C-terminal domain than the beta(TP) subunit due to their dissimilar interface configurations. Compared with the beta(TP) subunit, the beta(DP) subunit stably interacts with both the adjacent alpha(DP) and alpha(E) subunits. This sandwiched configuration in the beta(DP) subunit leads to strongly correlated motions between the beta(DP) and adjacent alpha subunits. The beta(DP) subunit exhibits an extensive network of highly correlated motions with bound ATP and the gamma subunit, as well as with the adjacent alpha subunits, suggesting that the structural changes occurring in the catalytically active beta(DP) subunit can effectively induce movements of the gamma subunit.