Simulations of Neck Linker Modified and One Head Loaded Kinesin

Abstract

Recently, Czovek et al. established a complete, thermodynamically consistent kinetic model for the two-headed homodimeric motor protein, kinesin. Computational simulations based on the model justified the crucial role of the conformational changes of the neck-linkers (NLs, the peptide chains connecting the two motor domains to the stalk) in the directional movement and force-generation of conventional kinesin. The model was able to reproduce a large number of experimental data (speed, dwell time distribution, randomness, processivity, hydrolysis rate, etc.) astonishingly well under normal as well as under highly unphysiological conditions. Moreover, it enabled a more detailed deconvolution of the mechanochemical cycle than it is experimentally possible. Having such a powerful model, we have applied it to modified versions of the wild-type kinesin, and reproduced (i) the speeds, processivities, and ATP consumption rates of NL modified kinesin; and (ii) the force-velocity relationship of the one-head-pulled kinesin. The good agreement between the simulations and the experiments further justify the legitimacy of the model, which thus provides a detailed understanding of the experimental observations and the basic mechanism of the operation of kinesin.