Elastic properties of dynein motor domain obtained from all-atom molecular dynamics simulations

Dyneins are large microtubule motor proteins that convert ATP energy to mechanical power. High-resolution crystal structures of ADP-bound cytoplasmic dynein have revealed the organization of the motor domain, comprising the AAA(+) ring, the linker, the stalk/strut and the C sequence. Recently, the ADP.vanadate-bound structure, which is similar to the ATP hydrolysis transition state, revealed how the structure of dynein changes upon ATP binding. Although both the ADP- and ATP-bound state structures have been resolved, the dynamic properties at the atomic level remain unclear. In this work, we built two models named 'the ADP model' and 'the ATP model', where ADP and ATP are bound to AAA1 in the AAA(+) ring, respectively, to observe the initial procedure of the structural change from the unprimed to the primed state. We performed 200-ns molecular dynamics simulations for both models and compared their structures and dynamics. The motions of the stalk, consisting of a long coiled coil with a microtubule-binding domain, significantly differed between the two models. The elastic properties of the stalk were analyzed and compared with the experimental results.