Periodic boundaries in Molecular Dynamics simulations: why do we need salt?

Abstract

AbstractMolecular dynamics (MD) simulations are usually performed by employing periodic boundary conditions (PBC). While this treatment of simulation system removes the necessity to treat the interactions with an otherwise artificial boundary, PBC also introduces additional constraints that need to be carefully considered for a robust and reliable simulation. Some of the issues pertaining to PBC are well explored and can be remedied by choosing a large enough unit cell, or by applying corrections to the generated trajectories. In current work, we study another artifact which cannot be alleviated by changing the box size. The artifact occurs due to the PBC imposed constraints affecting systems with permanent uncompensated dipoles, which is of particular relevance for lipid membrane simulations. Such dipoles often arise in many biologically-relevant setups, in particular those involving asymmetric lipid bilayers. The artifact manifests itself as an electric field formation in the simulation box which is counteracted by redistribution of mobile charge carriers (ions) and/or ordering of water dipoles. In the absence of ions, the artifact may cause strong water ordering, affecting thermodynamics of the studied system. This observation reveals a conceptually interesting effect of using explicit salt in MD simulations: ions help removing the unwanted periodicity-induced artifact occurring due to uncompensated electric dipoles. Therefore, we recommend adding mobile ions in molecular simulations whenever possible, and call for caution when simulating systems that require low salt concentration (or no salt at all), for example ion channel inactivation promoting conditions. In general, our findings are relevant for molecular simulations of any systems that contain uncompensated dipoles, that might occur more often than previously thought.