GROMACS version: 2021.1
GROMACS modification: None
Hi everyone,
I’m running a simulation to study the stability of a predicted Zn²⁺ coordination site from an AlphaFold3 structure. The Zn²⁺ is expected to form a tetrahedral geometry with three histidine NE atoms and a backbone oxygen from another residue. The initial geometry supports this, with distances and angles consistent with coordination.
However, after 50 ns of simulation using the CHARMM36 force field and TIP3P water, two of the coordinating atoms drift significantly—starting at ~0.2 nm and ending up around 0.6 nm. I suspect this may be due to inadequate parameterization of the residues interacting with Zn²⁺.
I minimized and equilibrated the system using distance restraints via a pulling setup, but once these are released, the coordination breaks down.
I’ve seen recommendations (e.g., from this paper: https://pubs.acs.org/doi/10.1021/acs.jcim.9b00407) to reparameterize coordinating residues, particularly histidines. However, this approach wouldn’t address the backbone oxygen involved in my system.
Has anyone faced a similar issue? Would reparameterizing only the histidines be sufficient, or is it necessary to include the backbone oxygen in the parametrization as well?
Thanks in advance!