Venue: C700, Lab3

Title: Effects of macromolecular crowding on protein dynamics and function

Speaker: Yuji Sugita (RIKEN Cluster for Pioneering Research) (website) 

Abstract: The concentration of macromolecules in the cell is known to be extremely high. This condition is often called “macromolecular crowding environments”, which affects protein structure, dynamics, and function significantly. Two major effects of macromolecular crowding environments have been often discussed: the excluded volume effects and weak non-specific molecular interactions. Multi-scale molecular dynamics (MD) simulation is a useful tool to investigate both effects, comparing the simulation with experimental results. It includes all-atom (AA) models and coarse-grained (CG) ones that use united particles for reducing the computational time. In addition, hybrid quantum mechanics/molecular mechanics (QM/MM) models allow us to investigate enzyme reactions, which include the bond formation and breaking in chemical reactions. We have carried out multi-scale MD simulations implemented in GENESIS software [1] on K and Fugaku supercomputers to understand macromolecular crowding effects on protein stability, dynamics, ligand-binding, and enzymatic reactions. The simulation results suggest that both excluded volume effects and non-specific molecular interactions are important for protein function in the cell. We also found dynamic population shifts of protein conformations in the crowded environments, which could change ligand-binding processes compared to those in dilute solution [2]. 

[1] Jung, Mori et al, Wiley Interdiscip. Rev. Comput. Mol. Sci. 2015, 5, 310-323; Kobayashi, Jung et al, J. Comp. Chem. 2017, 38, 2193-2206; Tan et al. PLoS Comp. Biol. 2022, 18, e1009578; Yagi et al. J. Phys. Chem. B 2021, 125, 4701-4713.

[2] I. Yu, et al. eLife 2016, 5, e19274; K. Kasahara, et al. Nature Communications 2021, 12, 4099.