Molecular Dynamics Study of the Effect of Polyamine on Microtubule Conformations

Abstract

Microtubules (MTs) play important roles in cell division, intracellular protein transport, and cell structure and movement in eukaryotic cells. MTs are hollow supramolecular polymers made of alpha and beta tubulin heterodimers. Microtubule assembly in cells require a proper orientation of tubulin molecules to the MTs end. Experiments have shown that polyamines such as spermine can facilitate the diffusion of tubulin dimers in the process of nuclei growth or MT growth. The mechanism of this aggregation is the bridging interaction of polyamines with highly negative C-terminal tail of tubulin surface which helps tubulin together. Recent experiments also show that with a high concentration of spermine, bundles of taxol-stabilized MTs undergo a shape transformation to bundles of inverted tubulin tubules. However, the molecular mechanism underlying the transformation is unclear. We performed all atom molecular dynamics simulation of tubulin clusters in presence of spermine in an explicit water solvent to study the structural dynamics of alpha/beta tubulin and microtubule protofilament. We discuss our results on the interaction between spermine and tubulin proteins and the effect of spermine on conformational dynamics of MT protofilaments.