Secondary Finite-Size Effects and Multibarrier Free Energy Landscapes in Molecular Simulations of Hindered Ion Transport

Ion
transport through nanoscale channels and pores is pivotal to
numerous natural processes and industrial applications. Experimental
investigation of the kinetics and mechanisms of such processes is,
however, hampered by the limited spatiotemporal resolution of existing
experimental techniques. While molecular simulations have become indispensable
for unraveling the underlying principles of nanoscale transport, they
all suffer from some important technical limitations. In our previous
works, we identified strong polarization-induced finite-size effects
in molecular dynamics simulations of hindered ion transport, caused
by spurious long-range interactions between the traversing ion and
the periodic replicates of other ions. To rectify these artifacts,
we introduced the ideal conductor/dielectric model (Icdm),
which treats the system as a combination of conductors and dielectrics
and constructs an analytical correction to the translocation free
energy profile. Here, we investigate some limitations of this model.
First, we propose a generalized approach based on Markov state models
that is capable of estimating translocation time scales in the thermodynamic
limit for free energy profiles with multiple comparable barriers.
Second, we identify a new category of polarization-induced finite-size
effects, which significantly alter the spatial distribution of nontraversing
ions in smaller systems. These secondary effects cannot be corrected
by the Icdm model and must be avoided by selecting sufficiently
large system sizes. Additionally, we demonstrate through multiple
case studies that finite-size artifacts can spuriously reverse expected
trends in ion transport kinetics. Our findings underscore the necessity
for careful selection of system sizes and the judicious application
of the Icdm model to rectify residual finite-size artifacts.