Comparison among Amber-ff14SB, Amber-ff19SB, and CHARMM36 Force Fields for Ionic and Electroosmotic Flows in Biological Nanopores

Molecular dynamics
has been widely used in nanofluidics
as it provides
an atomistic description of fluid transport that cannot be achieved
experimentally. The interactions among atoms are modeled by empirical
force fields whose reliability for a specific problem must be tested
against experimental evidence. Such validation is often difficult
to obtain in nanofluidics due to the challenges associated with measuring
nanoscale flows. Here, we systematically compare three popular force
fields (CHARMM36, Amber-ff14SB, both with TIP3P water, and Amber-ff19SB
with the OPC water) in terms of their electrohydrodynamical outputs.
As test cases, we used CytK and MspA, two biological nanopores employed
in sensing. For each nanopore, we simulated one cation-selective and
one anion-selective mutant. Our results show that while, overall,
the anion/cation selectivity and the direction of electroosmosis are
coherent across the force fields, quantitative differences are observed.
These differences cannot be simply explained by the transport properties
of the solution, such as the ion conductivity and viscosity. For narrow
pores such as MspA, these differences can become so significant as
to yield qualitatively different outcomes; for example, one force
field may predict no detectable electroosmosis while another shows
a clear electroosmotic flow.