Phase Behavior and Critical Point Scaling of a Coarse-Grained Protein Model Using Molecular Dynamics Simulations

Abstract

Cellular compartments are functional units that are essential in living organisms. Some organelles inside the cell are surrounded by a membrane, but many others are membraneless multicomponent assemblies of protein and RNA. These can exhibit liquid-like behavior and have been hypothesized to be the result of liquid-liquid phase separation. Intrinsically disordered proteins (IDPs) have been shown to play an important role in membraneless organelles, and their amino acid composition and sequence characteristics greatly influence their phase behavior. We develop a coarse-grained model for molecular dynamics simulations to study how interactions based on hydrophobicity between amino acids of IDPs shape their phase behavior. We vary the fraction and sequence of hydrophobic and hydrophilic monomers in linear chains and find that the tendency to phase separate increases with the number of hydrophobic particles, but highly depends on their position in the chain. We are able to incorporate this dependence into a new scaling parameter that allows us to predict the critical temperature of a chain based only on its sequence. Our findings are part of the effort to elucidate how sequence and amino acid content of IDPs influence their phase behavior. This can be applied to understanding the mechanisms of compartmentalization in the cell, as well as the formation of pathological protein aggregates in cells of neurodegenerative disease patients.