Developing Hybrid All-Atom and Ultra-Coarse-Grained Models to Investigate Taxol-Binding and Dynein Interactions on Microtubules.

Simulating the conformations and functions of biological macromolecules by using all-atom (AA) models is a challenging task due to expensive computational costs. One possible strategy to solve this problem is to develop hybrid all-atom and ultra-coarse-grained (AA/UCG) models of the biological macromolecules. In the AA/UCG scheme, the interest regions are described by AA models, while the other regions are described in the UCG representation. In this study, we develop the hybrid AA/UCG models and apply them to investigate the conformational changes of microtubule-bound tubulins. The simulation results of the hybrid models elucidated the mechanism of why the taxol molecules selectively bound microtubules but not tubulin dimers. In addition, we also explore the interactions of the microtubules and dyneins. Our study shows that the hybrid AA/UCG model has great application potential in studying the function of complex biological systems.