Structural change and nucleotide dissociation of Myosin motor domain: dual go model simulation

Abstract

We investigated the structural relaxation of myosin motor domain from the pre-power stroke state to the near-rigor state using molecular dynamics simulation of a coarse-grained protein model. To describe the spontaneous structural change, we propose a dual Gō-model-a variant of the Gō-like model that has two reference structures. The nucleotide dissociation process is also studied by introducing a coarse-grained nucleotide in the simulation. We found that the myosin structural relaxation toward the near-rigor conformation cannot be completed before the nucleotide dissociation. Moreover, the relaxation and the dissociation occurred cooperatively when the nucleotide was tightly bound to the myosin head. The result suggested that the primary role of the nucleotide is to suppress the structural relaxation.

FIGURE 1

Gō-potential: the solid line is dual Gō-potential energy profile for the ij pair. C₁₂ = U₂/U₁.

FIGURE 2

We chose (a) near-rigor structure, 1Q5G, and (b) pre-power stroke structure, 1VOM for structure 1 and 2, respectively. 1VOM contains the ADP·P_i analog, ADP·VO₄ (yellow). Also shown are the N-terminal (green), 50-kDa subdomain (red) and the converter (cyan) included in C-terminal subdomain (blue) that is connected to the lever arm.

FIGURE 3

(a) ATP and (b) coarse-grained ATP.

FIGURE 4

Relaxation time courses of dRMSD (from 1Q5G) (solid line) and Q_nucl. (dotted line) for five trajectories are shown. Different colors distinguish different runs. (a) k_p-n = 0.6; (b) k_p-n = 0.7.

FIGURE 5

Time sequence of dRMSD. The red line is the trajectory of the no-constraint simulation, and the other lines are trajectories of simulations in which nucleotide-binding site are constrained.

FIGURE 6

The relaxation-associated contacts satisfying the conditions P^ij(2 Å, 3 Å) < 0.3 and P^ij(0 Å, 2 Å) > 0.7 are shown. Residues included in the contacts are represented by spheres; residue numbers are indicated at the left. Green, red, and blue correspond to N-terminal, 50-kDa, and C-terminal subdomain, respectively.

FIGURE 7

dRMSD dependence of the contact formation rate of the relaxation-associated contacts at k_p-n = 0.7. Residue numbers of the contacts are indicated at the left.

FIGURE 8

Histogram of (a) the number of steps before dissociation and (b) the delay of the relaxation after the dissociation from 500 independent runs for each k_p-n.