Force Field and Membrane Patch Size Effects on Atomistic Models of Aquaporin‑7

Molecular dynamics (MD) simulations are a powerful tool
for characterizing
membrane-protein dynamics, yet their predictive accuracy critically
depends on the choice of force field and membrane representation.
Here, we present a systematic benchmark of the AMBER 14SB and CHARMM
36 m force fields across multiple bilayer sizes, using human aquaporin-7
(aquaglyceroporin-7; hAQP7) as a representative membrane protein system.
Both force fields maintained global structural integrity, but differed
markedly in their dynamic profiles: CHARMM 36 m sampled a broader
conformational space and produced more hydrated pore profiles, whereas
AMBER 14SB favored conformations closer to the crystallographic structure.
Lipid organization and packing also diverged, with CHARMM generating
more compact bilayers and AMBER yielding larger areas per lipid. The
membrane size exerted minimal influence on the structural or functional
descriptors, supporting the use of smaller, computationally efficient
membrane patches for equilibrium simulations. The hAQP7 monomers functioned
independently, without detectable cooperativity under the simulated
conditions. Collectively, these results highlight the substantial
impact of force-field selection on aquaporin dynamics and provide
practical guidance for designing accurate MD simulations of transmembrane
protein channels.