Martini without the twist: Unveiling a mechanically correct microtubule through bottom-up coarse-graining in Martini 3

Abstract

AbstractMicrotubules are essential cytoskeletal filaments involved in cell motility, division, and intracellular transport. These biomolecular assemblies can exhibit complex structural be-haviors influenced by various biophysical factors. However, simulating microtubule systems at the atomistic scale is challenging due to their large spatial scales. Here, we present an approach utilizing the Martini 3 Coarse-Grained (CG) model coupled with an appropriate elastic network to simulate microtubule-based systems accurately. By iteratively optimiz-ing the elastic network parameters, we matched the structural fluctuations of CG hetero-dimer building blocks to their atomistic counterparts. Our efforts culminated in a ∼ 200nm microtubule built with ∼ 6 million interaction-centers that could reproduce experimentally observed mechanical properties. Our aim is to employ these CG simulations to investigate specific biophysical phenomena at a microscopic level. These microscopic perspectives can provide valuable insights into the underlying mechanisms and contribute to our knowledge of microtubule-associated processes in cellular biology. With MARTINI 3 CG simulations, we can bridge the gap between computational efficiency and molecular detail, enabling in-vestigations into these biophysical processes over longer spatio-temporal scales with amino acid-level insights.