Amino acid transfer free energies reveal thermodynamic driving forces in biomolecular condensate formation.

ABSTRACT: The self-assembly of intrinsically disordered proteins into biomolecular condensates depends on their primary sequence, leading to sequence-dependent phase separation. Computational methods to study this behavior often rely on residue-level interaction potentials that estimate the propensity of amino acids to partition between the dilute and dense phases. While distribution coefficients would provide the most direct measure of these potentials, their unavailability has led to the use of proxies, most notably, hydropathy. However, recent studies have highlighted limitations in hydropathy-based models. Here, we address this fundamental gap by calculating the transfer free energies for amino acid side chain analogs moving from the dilute phase to the dense phase of biomolecular condensates. W

SUBMITTER: Rekhi S 

PROVIDER: S-EPMC12318233 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature