Multiscale Modeling of Microtubules and Actin Filaments

Abstract

AbstractComputational methods, as Molecular Dynamics (MD) simulations, have been used for years to gain insight into the properties of small fractions of microtubules (MTs) and actin filaments (F-actins). However, when considering an entire cytoskeleton filament, MD simulations lack of sufficient sampling of the phase space. In order to acquire adequate amount of data with statistical validity, a faster sampling technique is here developed and the bending stiffness of entire MTs and F-actins is computed. Our approach allows to propagate the information obtained at a fine-grained atomistic scale to a coarse grained (CG) scale. We perform MD simulations on representative units of the MT and F-actin. Then, we describe each monomer of these representative units with few interacting grains and employ them to build CG filaments: (1) entire MTs with lengths from ~300 nm to ~1.5 μm and (2) an entire actin filament of ~500 nm. The dynamics of these CG systems is analyzed using Brownian Dynamics (BD) simulations, allowing to achieve time and length scales hundreds of times higher than MD simulations. For our BD simulations an ad hoc force field is used, that matches MD atomistic fluctuations on the interaction potentials between pairs of CG beads. Results from the here proposed combination of atomistic MD simulations with coarse grained BD simulations are in agreement with experimental finding, providing more informative proofs of concept on how thermal fluctuations change interaction potentials among beads and on how the molecular rearrangements affect MT and F-actin rigidities.