Neighbor List Artifacts in Molecular Dynamics Simulations

Molecular dynamics (MD) simulations are widely used in biophysical research. To aid non-expert users, most simulation packages provide default values for key input parameters. In MD simulations using the GROMACS package with default parameters, we found large membranes to deform under the action of a semi-isotropically coupled barostat. As the primary cause, we identified overly short outer cutoffs and infrequent neighbor list updates that result in missed long-range attractive Lennard-Jones interactions. Small but systematic imbalances in the apparent pressure tensor then induce unphysical asymmetric box deformations that crumple the membrane. We also observed rapid oscillations in averages of the instantaneous pressure tensor components and traced these to the use of a dual pair list with dynamic pruning. We confirmed that similar effects are present in MD simulations of neat water in atomistic and coarse-grained representations. Whereas the slight pressure imbalances likely have minimal impact in most current MD simulations, we expect their impact to grow in studies of ever-larger systems, in particular in combination with anisotropic pressure coupling. We present measures to diagnose problems with missed interactions and guidelines for practitioners to avoid them, including estimates for appropriate values for the outer cutoff r_l and the number of time steps nstlist between neighbor list updates.