Studies of Conformational Changes of Tubulin Induced by Interaction with Kinesin Using Atomistic Molecular Dynamics Simulations.

The transition between strong and weak interactions of the kinesin head with the microtubule, which is regulated by the change of the nucleotide state of the head, is indispensable for the processive motion of the kinesin molecular motor on the microtubule. Here, using all-atom molecular dynamics simulations, the interactions between the kinesin head and tubulin are studied on the basis of the available high-resolution structural data. We found that the strong interaction can induce rapid large conformational changes of the tubulin, whereas the weak interaction cannot.

Run length distribution of dimerized kinesin-3 molecular motors: comparison with dimeric kinesin-1.

Kinesin-3 and kinesin-1 molecular motors are two families of the kinesin superfamily. It has been experimentally revealed that in monomeric state kinesin-3 is inactive in motility and cargo-mediated dimerization results in superprocessive motion, with an average run length being more than 10-fold longer than that of kinesin-1. In contrast to kinesin-1 showing normally single-exponential distribution of run lengths, dimerized kinesin-3 shows puzzlingly Gaussian distribution of run lengths.

All-atom molecular dynamics simulations reveal how kinesin transits from one-head-bound to two-heads-bound state.

Kinesin dimer walks processively along a microtubule (MT) protofilament in a hand-over-hand manner, transiting alternately between one-head-bound (1HB) and two-heads-bound (2HB) states. In 1HB state, one head bound by adenosine diphosphate (ADP) is detached from MT and the other head is bound to MT. Here, using all-atom molecular dynamics simulations we determined the position and orientation of the detached ADP-head relative to the MT-bound head in 1HB state.

Force dependence of unbinding rate of kinesin motor during its processive movement on microtubule.

Kinesin is a biological molecular motor that can move continuously on microtubule until it unbinds. Here, we studied computationally the force dependence of the unbinding rate of the motor. Our results showed that while the unbinding rate under the forward load has the expected characteristic of "slip bond", with the unbinding rate increasing monotonically with the increase of the forward load, the unbinding rate under the backward load shows counterintuitive characteristic of "slip-catch-slip bond": as the backward load increases, the unbinding rate increases exponentially firstly, then drops rapidly and then increases again.

Dynamics of tRNA dissociation in early and later cycles of translation elongation by the ribosome.

Deacylated tRNA dissociation from E site and aminoacyl-tRNA binding to the A site of the ribosome play a critical role in repetitive cycles of protein synthesis. Available experimental data showed that in the small range of aminoacyl-tRNA concentrations, during the first few cycles of translation elongation (initiation phase of translation) the E-site tRNA can be dissociated either before or after the A-site tRNA binding, while during the later cycles of elongation (elongation phase) the E-site tRNA is mostly dissociated before the A-site tRNA binding. Here, based on our proposed model of translation elongation we study analytically the dynamics of the E-site tRNA dissociation and A-site tRNA binding, providing quantitative explanations of the available experimental data in both the initiation and elongation phases.

Investigating role of conformational changes of microtubule in regulating its binding affinity to kinesin by all-atom molecular dynamics simulation.

Changes of affinity of kinesin head to microtubule regulated by changes in the nucleotide state are essential to processive movement of kinesin on microtubule. Here, using all-atom molecular dynamics simulations we show that besides the nucleotide state, large conformational changes of microtubule-tubulin heterodimers induced by strong interaction with the head in strongly binding state are also indispensable to regulate the affinity of the head to the tubulin. In strongly binding state the high affinity of the head to microtubule arises largely from mutual conformational changes of the microtubule and head induced by the specific interaction between them via an induced-fit mechanism.

Processivity of dimeric kinesin-1 molecular motors.

Kinesin-1 is a homodimeric motor protein that can move along microtubule filaments by hydrolyzing ATP with a high processivity. How the two motor domains are coordinated to achieve such high processivity is not clear. To address this issue, we computationally studied the run length of the dimer with our proposed model.