Analysis of the nucleotide-dependent conformations of kinesin-1 in the hydrolysis cycle

Kinesin-1 motion on a microtubule (MT) is still receiving a great attention due to its relevance in understanding molecular motion triggered by adenosine triphosphate (ATP) hydrolysis. Recent experimental data on kinesin-tubulin-nucleotide interactions have clarified some of the conformational details involved in the hydrolysis process [T. Mori et al., Nature (London) 450, 750 (2007)]. Specifically, fluorescence resonance energy transfer was used to measure the affinity of motor domains to tubulin heterodimers. Our work is directly devoted to understand and reproduce the main output of these experiments as well as to go beyond and give a global dynamical picture of the whole hydrolysis cycle. We predict that phosphate groups have the ability to confine to the tubulin domains in order to explain the delay between ATP hydrolysis and head detaching, which seems crucial for the achievement of processivity. In our approach me make use of chemical kinetics complemented with stochastic molecular simulations of the elements involved.