Chemical Biophysics Symposium 2018
Date:
The Chemical Biophysics Symposium (CBP) is a student-organized conference, which provides an informal venue for discussions on some of the most intriguing topics at the interface of chemistry, biology, and physics. Past symposia have been marked by a strong multi-disciplinary turnout and a reputation for lively debates, panel discussions, and question periods, not to mention lavish banquets and stellar lineups of noteworthy and engaging speakers.
I presented a poster Microtubule assembly and disassembly dynamics (MADDY) model.
ABSTRACT:
Microtubules (MTs), the primary components of the chromosome segregation machinery, can switch stochastically from growth to shortening, but the mechanisms of these processes at the molecular level are poorly understood. Here we developed a Microtubule Assembly and Disassembly DYnamics (MADDY) model, based upon a bead-per-monomer coarse-grained model of the αβ-tubulin heterodimers; in MADDY: an MT lattice is stabilized by the longitudinal and lateral interactions between the tubulin subunits; the protofilaments have a bending rigidity; different GTP or GDP-bound tubulin state-dependent equilibrium bending angles exist. The model was parameterized against the experimental rates of MT assembly and disassembly and the biomechanics of MT polymers. Using accelerated GPU based computations, we carried out Molecular Dynamics simulations for an MT fragment on the experimentally relevant timescale of several seconds. The MADDY model predicts that a growing MT tip, reaching 50-nm in length, forms a thin sheet curving away from the MT cylinder axis. The sheet gradually straightens as the number of protofilaments increases due to their lateral interactions, leading to the final cylindrical shape. The tip growth is accompanied by the formation of erroneous attachments and/or accumulation of “lattice defects”– lacking tubulin dimers that tend to self-correct over time. These findings offer a quantitative platform to link the molecular tubulin interaction characteristics with the dynamic behavior of MTs on the biologically-relevant scales of length and time. The molecularly-detailed computational MADDY model can be used to explore dynamic instability and the poorly understood mechanism of catastrophe and rescue of MT polymers.