Fig 1.
Structure of dynein motor domain.
(A) Structure models for the pre-power-stroke structure (left, modeled from 4RH7, the protein data bank id) and the post-power-stroke structure (modeled from 3VKH and 3J1T). (B) Cartoon view of the two structures with the definition of the eight multiple-basin systems. A unified color code is used to distinguish the eight modules throughout this paper; from N-terminus, the linker is in purple, the AAA1 is in blue, the AAA2 is in cyan, the AAA3 is in green, the AAA4 is in yellow, the MTBD/Stalk is in grey, the AAA5 is in orange, and the AAA6/C-terminal modules is in red.
Fig 2.
The power-stroke simulations in the standard setup.
(A) A representative trajectory of the reaction coordinates χ for the eight modules along the MD step. (B) The order map. Each square represents the probability that the transition in the region in the horizontal axis occurred before that in the region in the vertical axis over 30 trajectories. (C) The pair rate map representing k(b|a). (D) The sorted order map. The data in (B) is rearranged so that the summation in each column is in descending order. The same color code is used as in Fig 1.
Fig 3.
Analysis of the power-stroke process.
(A) A representative trajectory for the AAA1↑ simulation. (B) Local structural change at the interface between the linker and AAA1 in the standard setup simulation. The middle and the right structures represent the pre-power-stroke and an intermediate snapshot structure, respectively. The left-hand cartoon indicates the position of the structure within the entire motor domain. Important interactions are indicated by dashed lines. Atomistic model was reconstructed by the protocol given in Method. (C) Three examples of the conformational change in MTBD/Stalk along scaled time. (D) Average conformational change in MTBD/Stalk along scaled time for power-strokes. The time in each trajectory is scaled.
Fig 4.
Recovery-stroke simulations in the standard setup.
(A) A representative trajectory of the reaction coordinates χ for the eight modules along the MD step. (B) The order map. (C) The pair-rate map. (D) The sorted order map. Refer to the caption for Fig 2 for more information.
Fig 5.
Analysis of the recovery-stroke process.
(A) A representative trajectory for the AAA6↓ simulation. (B) Local structural change at the interface between AAA6/C-terminal module and the AAA1 in the standard setup simulation. The post-power-stroke structure (left) and an intermediate snapshot structure (right) are depicted. For the latter, the atomic structure was reconstituted from a coarse-grained snapshot. E4297 in the AAA6/C-terminal module and R2084 in the AAA1 module interact in the post-power-stroke structure, whereas they are apart in the intermediate structure. Atomistic model was reconstructed by the protocol given in Method. (C) Local structural change at the interface between the AAA6/C-terminal module (red for the post-power-stroke structure), salmon pink (100 x 104 MD step), and white (103 x 104 MD step)) and the AAA5 module (orange for the post-power-stroke structure), light orange (100 x 104 MD step), and white (103 x 104 MD step) in the standard setup simulation. Arrows labeled with 1 and 2 represent the sequential movement. (D) Three examples of the conformational change in MTBD/Stalk along scaled time. (E) Averaged conformational change in the MTBD/Stalk along scaled time for the forward (red) and recovery (blue) strokes. The time in each trajectory is scaled to be zero at the time of the AAA4 (AAA5) transitions and one at the time of the AAA5 (AAA4) transitions for the forward (recovery) strokes.
Fig 6.
Summary of the conformational change cascade in the power-stroke (left-half) and the recovery-stroke (right-half) processes.
The open and filled symbols represent the pre- and post-power-stroke states, respectively. Only for the MTBD, we used a three-state representation with the shaded circles being in a highly fluctuating state. The thickness of arrows indicates probabilities. The numbers associated with arrows represents the numbers of trajectories. Linker in purple, AAA1 in blue, AAA2 in cyan, AAA3 in green, AAA4 in yellow, stalk~MTBD in grey, AAA5 in orange, and AAA6~C-sequence in red.