Non converging Fmax in energy minimization

GROMACS version:2021
GROMACS modification: Yes/No

Dear GROMACS users,

I am currently trying to simulate a protein-ligand system using the charmm36-jul2021 force field.

In the energy minimization step, a large number of pdb files are being generated which majorly contain the solvent (water) molecules. I wonder how these files can be used.

Apart from this, the Fmax is not converging. We think that this could be because some atoms are too close and this is leading to large repulsive forces.

Can anyone who has some idea of what might be happening please comment? Thanks.

Regards,
Hemant

Hello there,

That sounds as if the minimization failed. It should not have generated ‘a large number of pdb files’.

Could you post the exact message that you get? Also, may I ask how did you generate your initial protein-ligand structure? It is possible that, as you pointed out, there are atoms so close that it leads to large repulsive forces.

Best regards

Hey Mikel,

Yes, you’re right. The minimization did fail.
Towards the end of minimization, it gave the following message:

Steepest Descents converged to machine precision in 3991 steps,
but did not reach the requested Fmax < 1000.
Potential Energy  =  2.6132226e+08
Maximum force     =  1.0053847e+05 on atom 9301
Norm of force     =  7.0071329e+02

The ligand was grafted into an APO protein and then minimized using a software by molsoft (ICM). I checked for clashes or atoms getting too close. Things seemed fine.

Interesting. What you are showing is that the EM procedure did not achieve its goal (Fmax < 1000), but that doesn’t mean necessarily that it failed (i.e. crashed).

Do try some of the fixes that some other users pointed out in this post

You can also try to minimize individually the ligand and the APO protein, only for the sake of checking that their individual geometries are not problematic.