Data-driven equation-free dynamics applied to many-protein complexes: The microtubule tip relaxation

Area of Science:

• Biophysics
• Computational Biology
• Cell Biology

Background:

• Microtubules are essential eukaryotic cytoskeleton components involved in mitosis and transport.
• Microtubule dynamic instability, crucial for their function, is linked to GTP hydrolysis in β-tubulin.
• Simulating microtubule tip dynamics at an all-atom level is computationally challenging.

Purpose of the Study:

• To investigate the structural differences between GDP- and GTP-complexed microtubule tips.
• To overcome computational limitations in simulating large microtubule systems.
• To refine the understanding of factors underlying microtubule dynamic instability.

Main Methods:

• Employed the "equation-free" multiscale computational method to accelerate simulations.
• Utilized large microtubule lattice systems (∼21-38 million atoms).
• Combined coarse-projective equation-free jumps with all-atom molecular dynamics simulations.

Main Results:

• Achieved nearly double the computational efficiency for relaxed all-atom conformations.
• Generated 5.875 μs of effective simulation trajectories for GDP- and GTP-complexed MT tips.
• Exposed subtle structural differences in MT tips based on GDP/GTP binding and revealed lateral interactions.

Conclusions:

• The study provides a refined understanding of microtubule dynamic instability.
• The "equation-free" multiscale method is robust and generalizable for large biomolecular systems.
• This approach enables future explorations of biomolecular systems at atomic resolution.