Relating nucleotide-dependent conformational changes in free tubulin dimers to tubulin assembly.

The complex dynamic behavior of microtubules (MTs) is believed to be primarily due to the αβ-tubulin dimer architecture and its intrinsic GTPase activity. Hence, a detailed knowledge of the conformational variations of isolated α-GTP-β-GTP- and α-GTP-β-GDP-tubulin dimers in solution and their implications to interdimer interactions and stability is directly relevant to understand the MT dynamics. An attempt has been made here by combining molecular dynamics (MD) simulations and protein-protein docking studies that unravels key structural features of tubulin dimer in different nucleotide states and correlates their association to tubulin assembly. Results from simulations suggest that tubulin dimers and oligomers attain curved conformations in both GTP and GDP states. Results also indicate that the tubulin C-terminal domain and the nucleotide state are closely linked. Protein-protein docking in combination with MD simulations suggest that the GTP-tubulin dimers engage in relatively stronger interdimer interactions even though the interdimer interfaces are bent in both GTP and GDP tubulin complexes, providing valuable insights on in vitro finding that GTP-tubulin is a better assembly candidate than GDP-tubulin during the MT nucleation and elongation processes.