Nonspecific Yet Selective Interactions Contribute to Small Molecule Condensate Binding.

ABSTRACT: Biomolecular condensates are essential in various cellular processes, and their misregulation has been demonstrated to underlie disease. Small molecules that modulate condensate stability and material properties offer promising therapeutic approaches, but mechanistic insights into their interactions with condensates remain largely lacking. We employ a multiscale approach to enable long-time, equilibrated all-atom simulations of various condensate-ligand systems. Systematic characterization of the ligand binding poses reveals that condensates can form diverse and heterogeneous chemical environments with one or multiple chains to bind small molecules. Unlike traditional protein-ligand interactions, these chemical environments are dominated by nonspecific hydrophobic interactions. Nevertheles

SUBMITTER: Wang C 

PROVIDER: S-EPMC11665859 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature