MICROTUBULE-KINESIN MECHANICS BY MOLECULAR MODELING

Abstract

The cellular cytoskeleton contains microtubules which function both as fundamental structural elements as well as motor protein tracks. While the structural property is connected to the properties of the tubulin dimer, its interactions with surrounding dimers and the geometric organization within the microtubule, the transport track properties are related to the interactions between the tubulin dimer and kinesin.Based on the atomistic structures of kinesin and the tubulin dimer, we used molecular modeling to examine the interaction energy and force as function of a spatial distance of separation. From the results, elastic constants describing the system stiffness are obtained. By using the results related to the structure alone, a model of a 1 μm long microtubule is constructed as a network of elastic elements, and its mechanical properties were obtained via finite element method and compared to experimental results.Concerning microtubule-kinesin complex, the interaction strength during a complete cycle of ATP hydrolysis was investigated. As expected, the affinity between the proteins is modulated by the type of nucleotide occupying the nucleotide binding pocket of the motor protein. The work underscores how molecular modeling can provide fundamental protein information in terms of the relation between mechanical properties and structural changes.