Study On Docking Process Of Kinesin’s β10

Kinesin is a kind of molecular motor and an indispensable protein in eukaryotes.It can carry organelles and biological molecules along microtubules,and accurately deliver these "goods" to where they are needed.The force generation mechanism of driving proteins along microtubules is one of the most advanced topics in the field of biology and biophysics.The neck linker is the key component of kinesin on the force generation mechanism of walking along microtubules.Neck linker docking to the motor domain directly affects the movement of kinesin on microtubules.The neck linker of kinesin is a βband consisting of about 14 amino acids,which is mainly divided into three parts: the first three amino acids in the initial part,β9 and β10.There are three parts of the neck linker docking to the motor domain.The first part is Extra Turn,which is the first three amino acids of the neck linker forming a semi-helical structure.The second part is CNB,which is formed by β9 of the neck linker and β0 in the N-terminal of the motor domain.The third part is β10 which is docked to the motor domain by forming four hydrogen bonds with the motor domain.This paper introduces the mechanism of the first two parts of the neck linker docking to the motor domain in detail,and the main research about this paper is the mechanism of the third part of the neck linker(β10)docking to the head of the motor.The process of β10 in the neck linker of kinesin is studied by molecular dynamics simulation.The β10 docking to the motor domain is accomplished by the formation of four skeleton Hydrogen bonds.Although the four skeleton hydrogen bonds are formed in the same way,their stability and effective mechanical strength are quite different.Molecular dynamics simulations show that these skeleton hydrogen bonds are vulnerable along water attacking.The skeleton hydrogen bond in the N-terminal of β10 exhibits super high strength stability because hydrophobic and polar groups around the skeleton hydrogen bond protect and cooperate with it.The four skeleton hydrogen bonds of β10 exhibit a mechanical gradient gradually decreasing from N-terminal to C-terminal.The process of β10 in neck linker docking to the motor domain is also a gradual process from N-terminal to C-terminal.The key to the realization of the whole process of β10 docking to the motor domain is the formation of the N-terminal skeleton hydrogen bond.We have carefully studied the formation process of this key hydrogen bond through molecular dynamics simulation.We found that before the formation of the hydrogen bond,the hydrogen bond sites will form a water bridge with water molecules.The formation of the water bridge will lock the distance between hydrogen and oxygen atoms of the skeleton hydrogen bond sites in the distance that can form hydrogen bonds,thus forming skeleton hydrogen bonds.The formation of the N-terminal skeleton hydrogen bond of β10 greatly mentions the formation probability of the other three skeleton hydrogen bonds,so that the whole docking process of β10 can be realized.The results of this study are very important for understanding the force generation mechanism of walking along microtubules.