Condensation/dissolution has become a widely acknowledged biological macromolecular assembly phenomenon in subcellular compartmentalization. MARTINI force field offers a coarse-grained protein model with a resolution that preserves molecular details with an explicit (CG) solvent. Despite its relatively higher resolution, it can still achieve condensate formation in reasonable computing time with explicit solvent and ionic species. Therefore, it is highly desirable to tune this force field to be able to reproduce the experimentally observed properties of the condensate formation. In this work, we studied the condensate formation of the low-sequence complexity (LC) domain of FUsed in Sarcoma (FUS) protein using a MARTINI 3 force field by systematically modifying (increasing) the protein-water interaction strength and varying salt concentration. We found that the condensate formation is sensitive both to the protein-water interaction strength and the presence of salt. While the unmodified MARTINI force field yields a complete collapse of proteins into one dense phase (i.e., no dilute phase), we reported a range of modified protein-water interaction strength that is capable of capturing the experimentally found transfer free energy between dense and dilute phases. We also found that the condensates lose their spherical shape upon the addition of salt, especially when the protein-water interactions are weak. Inter-chain amino acid contact map analysis showed one explanation for this observation: the protein-protein contact fraction reduces as salt is added to systems (when the protein-water interactions are weak), consistent with electrostatic screening effects. This reduction might be responsible for the condensates becoming nonspherical upon the addition of salt by reducing the need for minimizing interfacial area. However, as the protein-water interactions become stronger to the extent that makes the transfer free energy agree well with experimentally observed transfer free energy, we found an increase in protein-protein contact fraction upon the addition of salt, consistent with the salting-out effects. Therefore, we concluded that there is an intricate balance between screening effects and salting-out effects upon the addition of salt and this balance is highly sensitive to the strength of protein-water interactions.
