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

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.

Automated summary

The study found that TIP4P/2005 is the only water model that accurately simulates the fast association/dissociation dynamics of ubiquitin protein and accurately identifies its binding surface, highlighting the critical role of water models in describing protein self-association processes.