Effect of the Water Model in Simulations of Protein–Protein Recognition and Association

Abstract

We study self-association of ubiquitin and the disordered protein ACTR using the most commonly used water models. We find that dissociation events are found only with TIP4P-EW and TIP4P/2005, while the widely used TIP3P water model produces straightforward aggregation of the molecules due to the absence of dissociation events. We also find that TIP4P/2005 is the only water model that reproduces the fast association/dissociation dynamics of ubiquitin and best identifies its binding surface. Our results show the critical role of the water model in the description of protein–protein interactions and binding.