Clustering of RNA\nPolymerase II C‑Terminal\nDomain Models upon Phosphorylation

RNA polymerase II\n(Pol II) C-terminal domain (CTD) is\nknown to\nhave crucial roles in regulating transcription. CTD has also been\nhighly recognized for undergoing phase separation, which is further\nassociated with its regulatory functions. However, the molecular interactions\nthat the CTD forms to induce clustering to drive phase separations\nand how the phosphorylation of the CTD affects clustering are not\nentirely known. In this work, we studied the concentrated solutions\nof two heptapeptide repeat (2CTD) models at different phosphorylation\npatterns and protein and ion concentrations using all-atom molecular\ndynamics simulations to investigate clustering behavior and molecular\ninteractions driving the cluster formation. Our results show that\nsalt concentration and phosphorylation patterns play an important\nrole in determining the clustering pattern, specifically at low protein\nconcentrations. The balance between inter- and intrapeptide interactions\nand counterion coordination together impact the clustering behavior\nupon phosphorylation.