posted on 2024-02-28, 18:38authored byIlona
C. Unarta, Siqin Cao, Eshani C. Goonetilleke, Jiani Niu, Samuel H. Gellman, Xuhui Huang
Liquid–liquid phase separation mediated by proteins
and/or
nucleic acids is believed to underlie the formation of many distinct
condensed phases, or membraneless organelles, within living cells.
These condensates have been proposed to orchestrate a variety of important
processes. Despite recent advances, the interactions that regulate
the dynamics of molecules within a condensate remain poorly understood.
We performed accumulated 564.7 μs all-atom molecular dynamics
(MD) simulations (system size ∼200k atoms) of model condensates
formed by a scaffold RNA oligomer and a scaffold peptide rich in arginine
(Arg). These model condensates contained one of three possible guest
peptides: the scaffold peptide itself or a variant in which six Arg
residues were replaced by lysine (Lys) or asymmetric dimethyl arginine
(ADMA). We found that the Arg-rich peptide can form the largest number
of hydrogen bonds and bind the strongest to the scaffold RNA in the
condensate, relative to the Lys- and ADMA-rich peptides. Our MD simulations
also showed that the Arg-rich peptide diffused more slowly in the
condensate relative to the other two guest peptides, which is consistent
with a recent fluorescence microscopy study. There was no significant
increase in the number of cation–π interactions between
the Arg-rich peptide and the scaffold RNA compared to the Lys-rich
and ADMA-rich peptides. Our results indicate that hydrogen bonds between
the peptides and the RNA backbone, rather than cation–π
interactions, play a major role in regulating peptide diffusion in
the condensate.