I am performing a molecular dynamics simulation from CRBN protein (PDB ID: 4tz4), which contain a ZN binding site composed of four cysteines. The main goal is understanding the chemical and biological changes in the Zn binding site from this protein when Cys391-to-Arg (C391R) substitution occur. For this, we performed the geometry optimization of the complex of four cysteines and Zn using DFT calculations on Gaussian 16 suite. Then, we put the coordinates obtained through DFT on the PDB format, and we will perform molecular dynamics simulation to obtain results in the perspective of the whole protein.

Now, I am using Gromacs to perform the MD simulation, but there is an error on my simulation during the NVT stabilization. This is the error message:

"Back Off! I just backed up step0c.pdb to ./#step0c.pdb.1# Wrote pdb files with previous and current coordinates ^Mstep 0 WARNING: Listed nonbonded interaction between particles 4204 and 4221 at distance 4.402 which is larger than the table limit 2.029 nm.

This is likely either a 1,4 interaction, or a listed interaction inside a smaller molecule you are decoupling during a free energy calculation. Since interactions at distances beyond the table cannot be computed, they are skipped until they are inside the table limit again. You will only see this message once, even if it occurs for several interactions.

IMPORTANT: This should not happen in a stable simulation, so there is probably something wrong with your system. Only change the table-extension distance in the mdp file if you are really sure that is the reason."

I am thinking about the reason for this error, and this could be because the force field which I am using to perform the simulation (amber03), but I am not sure about that. It is proper to mention that the atoms in which there is the error are the C of the residues (Lys324 and Gly325) which are between two of the Cys that form the Zn binding site.

Please, can anyone help me with this issue? Thank you very much