TITLE: Revealing the mechanisms of molecular motors’ motility by using computational approaches

ABSTRACT: Dynein is a molecular motor for cargo transportation and force generation in cells. Dysfunction of dynein is associated with many diseases, such as ciliopathies, lissencephaly and other neurodegeneration disorders. Understanding the functions of dynein is crucial for developing new treatments of such diseases. Electrostatic interactions play important roles in proteins including dyneins. A lot of efforts have been made to study the electrostatic interactions in biological systems. However, it is extremely challenging to accurately calculate the electrostatic interactions in large biological systems such as dynein. We have developed a novel multi-scale simulation approach which is used to study dynein’s motion along microtubules. The electrostatic binding funnel around microtubule is observed, which drags the dynein to the binding pocket. The electrostatic forces on dynein residues form a torsion which reorients the dynein when it is in an un-native orientation. Furthermore, the electrostatic component of the binding energy of dynein and microtubule strongly affects the velocity and run length of the dynein. These results reveal the mechanisms of dynein’s motility and functions along microtubule, which shed light on treatments of molecular motor related diseases.