Modeling phase separation of proteins with compact native states using LatticePy, a package for MCMC simulations on lattices

Liquid-Liquid Phase Separation (LLPS) of proteins has proven to be a ubiquitous feature inside cells, playing critical roles in many biological pathways. While phase separation is commonly observed for intrinsically disordered proteins, predicting if and when well-folded proteins may also undergo LLPS is an open problem. To begin to address this knowledge gap, here we provide the first open-source scalable, replicable, and easy-to-use package, LatticePy, to simulate oligomerization and phase separation for any given lattice-protein sequence. Implementing standard moves for lattice proteins and simple energy functions, we explore the conditions under which proteins with a well-defined, compact native state instead adopt unfolded conformations as part of multiprotein oligomers or condensates.