Seminarium "Modeling of Complex Systems"

The teleonomic criterion, proposed by complexity scientist David Krakauer, defines complex systems by their ability to gather and process information to pursue goals. This criterion distinguishes complex systems from "simple" causal ones. It can be argued that the collective network of microtubules (MTs), which constitutes a part of the cytoskeleton, along with MT-associated proteins, meets this criterion. The mitotic spindle, for instance, is a goal seeking protein machine made of MTs that accurately locates, captures, and separates chromosomes during mitotic division. This complex behavior is rooted in the MT feature of dynamic instability — an abrupt, stochastic switching between polymerization and depolymerization.A complete molecular explanation for this phenomenon remains elusive. Moreover, much of the conventional understanding invoking changes in tubulin monomer shape upon GTP hydrolysis conflicts with recent experimental results. To address this gap in knowledge, we applied a multiscale modeling approach that combines high-resolution and coarse-grained computational methods to investigate MT tip structure and dynamics. Our work employs two complementary strategies:1. High-Resolution Dynamics: We performed exhaustive 4-microsecond all-atom molecular dynamics (MD) simulations of a 224-protein MT plus-end tip.2. Coarse-Grained Dynamics: We used two distinct coarse-grained approaches:(i) Iterative Boltzmann Inversion to parameterize a protein-resolution model and extrapolate the behavior of the MT plus-end tip using Brownian dynamics;(ii) data-driven "equation-free" approach to extend the all-atom MD trajectories to an unprecedented 6 microseconds.Our results confirm that both GDP- and GTP-bound MT tips exhibit an outward bending of protofilament clusters into characteristic ram's horn-like structures. Crucially, our results expose subtle yet important differences between the two nucleotide states that align with experimental cryo-ET images. However, whether these subtle differences are sufficient to fully explain MT dynamic instability remains an open question.

The seminar will be held in hybrid mode: in room 1.40 (IPC PAS) Join Zoom Meetinghttps://uw-edu-pl.zoom.us/j/96378632993?pwd=MVgdPR80oKaE4pjLufb2NCtg6ql4Ax.1Meeting ID: 963 7863 2993Passcode: 569551