Simulating the Kinesin Walk: A Small Step towards Understanding Dementia

Dementia results from neurode-generation, a cause of which is the failure of axonal transport. Axonal transport is the systematic movement of vital cargo between the neuron cell body and the synapse. The engines powering this transport are motor proteins, molecular nanomachines. Kinesin-1 (conventional kinesin) is a motor protein that carries cargo to the synapse by walking along microtubule tracks. Its twin motor domains (heads) alternately bind the microtubule, derive energy from hydrolysing ATP, and step forward. This motion cannot be directly observed so the details are a matter of debate based on indirect experimental observations. A rule-based, spatial computer simulation has been built to better understand how kinesin walks. Results show a preference for rectified Brownian motion over a power stroke mechanism for normal stepping. A small step towards investigation of transport failure - placing a blockage on the microtubule - indicates a possible novel gating mechanism for kinesin.