Prediction of small-molecule partitioning into biomolecular condensates from simulation.

ABSTRACT: Predicting small-molecule partitioning into biomolecular condensates is key to developing drugs that selectively target aberrant condensates. However, the molecular mechanisms underlying small-molecule partitioning remain largely unknown. Here, we first exploit atomistic molecular dynamics simulations of model condensates to elucidate physicochemical rules governing small-molecule partitioning. We find that while hydrophobicity is a major determinant, solubility becomes a stronger regulator of partitioning in more polar condensates. Additionally, more polar condensates exhibit selectivity toward certain compounds, suggesting that condensate-specific therapeutics can be engineered. Building on these insights, we develop minimal models (MAPPS) for efficient prediction of small-molecule parti

SUBMITTER: Emelianova A 

PROVIDER: S-EPMC11908252 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature