%0 Journal Article
%T A High-Throughput Approach to Phase Separation of Disordered Proteins
%J -
%D 2019
%R https://doi.org/10.1016/j.bpj.2018.11.1906
%X The process of phase separation has proven to be indispensable in biology, taking the form of stress granules, processing bodies, nucleoli, and many others. The utility of these assemblies, termed membraneless organelles, continues to be explored and can be advantageous over their membrane-bound counterparts in a number of ways. Many systems which undergo liquid-liquid phase separation (LLPS) are driven by weak, non-specific multivalent interactions, and commonly involve intrinsically disordered proteins and regions (IDPs and IDRs). Using molecular simulations, we are able to explore the molecular driving forces of LLPS and its dependence on the protein sequence to help understand what interactions are important in different systems. We find that for some sequences such as the low-complexity domain of Fused in Sarcoma (FUS LC), phase separation is driven largely by weak, non-specific interactions between different amino acids throughout the full sequence. For other sequences, such as LAF-1, we find that specific regions of the sequence are important for driving the phase separation. For the purpose of designing new peptide sequences and understanding changes to phase behavior in response to perturbations to the system, we have assembled a coarse-grained modeling framework which allows us to rapidly screen through sequence space using different models while preserving sequence information[1]. Finally, using this improved methodology, we introduce several extensions of the coarse-grained model to more accurately represent features relevant to the field of IDP phase separation, such as post-translational modifications and other non-canonical amino acids
%U https://www.cell.com/biophysj/fulltext/S0006-3495(18)33171-0