However, simulations of single chains can of course not inform us about the collective behavior and correlations of many polypeptide chains in condensates. These aspects are particularly important if one aims at deciphering the role of the configurational entropy of the polypeptide as a driving force for PS, which is a particularly challenging topic due to the notoriously slow convergence of the protein entropy due to incomplete sampling of all relevant conformational states on the timescales accessible to all-atom simulations. Polyansky et al. performed single-chain and multi-chain atomistic MD simulations of the intrinsically disordered N-terminal fragment of the S. cerevisiae Lge1 protein (Lge1 1-80 ) [64]. Using a mutual information spanning tree approach to extract configurational entropies from their microsecond timescale simulations, they reported that the protein configurational entropy is lower in the condensate than in dilute solution, with the polypeptide chains adopting more compact conformations in the condensate. Hence, at least for Lge1 1-80 , PS seems to be driven by favorable preferential interactions in the condensate and not by protein configurational entropy. Qualitatively similar conclusions were drawn by Mukherjee and Schäfer for the FUS low complexity domain . However, given the slow convergence of conformational sampling especially in the condensate phase, it would be desirable to extend the sampling beyond the microsecond timescale, and if possible apply enhanced sampling methods to investigate the long-term (equilibrium) limits. In general, it is not clear whether the configurational entropy change of a polypeptide chain upon PS will be favorable or unfavorable -it probably depends on the system under investigation, and a systematic exploration would be worthwhile.