Microtubule “dynamic instability,” the abrupt switching from assembly to disassembly caused by the hydrolysis of GTP to GDP within the β subunit of the αβ-tubulin heterodimer, is necessary for vital cellular processes such as mitosis and migration. Despite existing high-resolution structural data, the key mechanochemical differences between the GTP and GDP states that mediate dynamic instability behavior remain unclear. Starting with a published atomic-level structure as an input, we used multiscale modeling to find that GTP hydrolysis results in both longitudinal bond weakening (~ 4 kBT) and an outward bending preference (~ 1.5 kBT) to both drive dynamic instability and give rise to the microtubule tip structures previously observed by light and electron microscopy. More generally, our study provides an example where atomic level structural information is used as the sole input to predict cellular level dynamics without parameter adjustment.
Bibliographical noteFunding Information:
The authors thank Dr. Jonathan Sachs for advice and helpful discussions. This study was supported by National Institutes of Health under Award Number RF1-AG053951 and the Institute for Engineering in Medicine (IEM) award at the University of Minnesota to DJO. The authors acknowledge the Extreme Science and Engineering Discovery Environment (XSEDE), Comet system at the San Diego Supercomputing Center (SDSC) and Bridges system at the Pittsburgh Supercomputing Center (PSC) through allocation MCB160060, and the Minnesota Supercomputing Institute (MSI) at the University of Minnesota for providing resources that contributed to the research results reported within this paper.
© 2021, The Author(s).
- Brownian dynamics
- Molecular dynamics
- Thermokinetic modeling
PubMed: MeSH publication types
- Journal Article