Atomistic Insights into Disordered Proteins and Condensates via Molecular Simulations

Abstract

Biomolecular condensates formed by intrinsically disordered proteins (IDPs) play essential roles in cellular organization and function, attracting broad scientific interest. In addition to experimental approaches, molecular dynamics simulations—particularly atomistic simulations—serve as powerful tools for gaining mechanistic insights into IDP conformations and inter- and intramolecular interactions within condensates. In this work, we developed a multiscale simulation strategy that balances efficiency and accuracy by combining coarse-grained and atomistic modeling. We further applied dimensionality reduction techniques to extract meaningful features from high-dimensional simulation data. Using this integrated framework, we investigated three scientific problems: (1) the sequence-dependent conformational ensembles of IDPs, (2) nonspecific yet selective condensate–drug interactions, and (3) the mechanism of formation of monocomponent, multiphasic condensates formed by tetrapeptide sequences.