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

Agustí Emperador; Ramon Crehuet; Elvira Guàrdia

doi:10.3390/polym13020176

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

Polymers (Basel). 2021 Jan 6;13(2):176. doi: 10.3390/polym13020176.

Authors

Agustí Emperador¹, Ramon Crehuet², Elvira Guàrdia¹

Affiliations

¹ Department of Physics, Universitat Politècnica de Catalunya, B4-B5 Campus Nord, Jordi Girona 1-3, 08034 Barcelona, Spain.
² CSIC-Institute for Advanced Chemistry of Catalonia (IQAC), Jordi Girona 18-26, 08034 Barcelona, Spain.

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.

Keywords: ACTR; molecular dynamics; protein association; protein–protein interaction; ubiquitin; water model.