Determine the cause of the late loss of the KcsA contact column

Determine whether the late loss of the contiguous, dehydrated K+ contact column in UBio-MolFM seed 126 is caused by a potential-specific rare fluctuation, membrane drift, or another mechanism, rather than by an artifact of the simulation protocol.

Background

The 108,964-atom KcsA simulations produced a contiguous, dehydrated four-ion column in four of five UBio-MolFM replicas. One replica, seed 126, maintained the contact column for approximately 700 ps before the column opened and the ions became more widely separated. During and before this event, both membrane hydration and protein backbone RMSD changed, making it unclear whether the transition reflects an intrinsic fluctuation of the learned potential or a protocol- or system-specific artifact.

The authors explicitly decline to interpret this single-trajectory event because one replica cannot distinguish a rare physical fluctuation from a defect associated with membrane drift or other collective relaxation. Resolving the cause would require additional long simulations, including trajectories under the semi-isotropic barostat used for the classical references.