Abstract
Microtubules are the main components of mitotic spindles, and are the pillars of the cellular cytoskeleton. They perform most of their cellular functions by virtue of their unique dynamic instability processes which alternate between polymerization and depolymerization phases. This in turn is driven by a precise balance between attraction and repulsion forces between the constituents of microtubules (MTs)—tubulin dimers. Therefore, it is critically important to know what contributions result in a balance of the interaction energy among tubulin dimers that make up microtubules and what interactions may tip this balance toward or away from a stable polymerized state of tubulin. In this paper, we calculate the dipole–dipole interaction energy between tubulin dimers in a microtubule as part of the various contributions to the energy balance. We also compare the remaining contributions to the interaction energies between tubulin dimers and establish a balance between stabilizing and destabilizing components, including the van der Waals, electrostatic, and solvent-accessible surface area energies. The energy balance shows that the GTP-capped tip of the seam at the plus end of microtubules is stabilized only by kcal/mol, which can be completely reversed by the hydrolysis of a single GTP molecule, which releases kcal/mol and destabilizes the seam by an excess of kcal/mol. This triggers the breakdown of microtubules and initiates a disassembly phase which is aptly called a catastrophe.
Highlights
One of the most interesting features of microtubules (MTs) is their dynamic instability
Several models have been developed in recent years, trying to explain how microtubule dynamics is regulated; i.e., the parameters causing growth or shrinkage, and how cells are able to modify such parameters according to their needs and means
We found that lateral contacts are stronger than longitudinal ones. We followed it by a complete microtubule simulation, resulting in a molecular mechanics/generalized Born surface area (MMGBSA) estimation of the tubulin binding energies [6]
Summary
One of the most interesting features of microtubules (MTs) is their dynamic instability. We previously calculated the contribution of hydrogen bonds to the lateral and longitudinal tubulin binding energies using density functional theory [5], showing that they represent a major factor contributing to MT stability.
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