A Study Of The Mechanical Characteristics Of Kinesin’s Neck Coiled Coil

Kinesin is a protein superfamily, of which kinesin-1(abbreviated to kinesin) is thesmallest motor protein in organism known to date. Kinesin is crucial for mitosis andorganelle transportation in cells. In eukaryotic cells, kinesin exists as a dimer with twomotor heads connected by a coiled-coil stalk. Experiments have shown that the neck coiledcoil of kinesin exhibits a surprising mechanical stability, which will not be open during theentire walking cycle of kinesin. The origin of this surprising mechanical stability, however,is still unclear.NAMD is an open source molecular dynamics software which can be performed athigh efficiency in parallel for multiple processors and can be widely applied to largemolecular systems in the calculation with long time in recent years.In order to explore the origin of the surprising mechanical stability of kinesin’s neckcoiled coil, we extract the neck coiled coil structure from the crystal structure of3KIN, andthen, using NAMD software, perform molecular dynamics simulation and optimization.Weanalyzed the characteristics of the four stages of the neck coiled coil opening displayed inthe simulation trajectories, and found the reasons for transitions from each stage to the next.We also found that the design of the heptad repeat of the neck coiled coil is highly exquisitethat the combination of the hydrophobic and hydrophilic amino acids results in a specialmechanical effect. Especially, the long hydrophobic side chains of the hydrophilic aminoacids have a strong hydrophobic effect together with those hydrophobic residues, so as toensure a pair of hydrogen atoms on the tyrosines at the end of the first heptad structure toform a steric hindrance against the unwinding of the coiled coil, i.e., the special cooperationbetween hydrophobic effect and steric hindrance is the origin of the surprising mechanicalstability of the neck coiled coil. These results provide new insights into the understandingof the characteristics of kinesin’s neck coiled coil and the kinesin mechanism.