Heterogeneous\nSlowdown of Dynamics in the Condensate\nof an Intrinsically Disordered Protein

The high concentration of proteins and other biological\nmacromolecules\ninside biomolecular condensates leads to dense and confined environments,\nwhich can affect the dynamic ensembles and the time scales of the\nconformational transitions. Here, we use atomistic molecular dynamics\n(MD) simulations of the intrinsically disordered low complexity domain\n(LCD) of the human fused in sarcoma (FUS) RNA-binding protein to study\nhow self-crowding inside a condensate affects the dynamic motions\nof the protein. We found a heterogeneous retardation of the protein\ndynamics in the condensate with respect to the dilute phase, with\nlarge-amplitude motions being strongly slowed by up to 2 orders of\nmagnitude, whereas small-scale motions, such as local backbone fluctuations\nand side-chain rotations, are less affected. The results support the\nnotion of a liquid-like character of the condensates and show that\ndifferent protein motions respond differently to the environment.