Non converging Fmax in energy minimization using charmm36-jul2021 version

User discussions
1

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. Along with this, the Fmax is also not converging.
I had raised this issue earlier in

By now, I have tried using the new force field in many Protein-Ligand systems and in none of them did I succeed.
Here is the em.mdp file that I used.

title		    = Minimization	; Title of run

; Parameters describing what to do, when to stop and what to save
integrator	    = steep		; Algorithm (steep = steepest descent minimization)
emtol		    = 1000.0  	; Stop minimization when the maximum force < 10.0 kJ/mol
emstep          = 0.01      ; Energy step size
nsteps		    = 50000	  	; Maximum number of (minimization) steps to perform

; Parameters describing how to find the neighbors of each atom and how to calculate the interactions
nstlist		    = 1		        ; Frequency to update the neighbor list and long range forces
cutoff-scheme   = Verlet
ns_type		    = grid		    ; Method to determine neighbor list (simple, grid)
rlist		    = 1.2		    ; Cut-off for making neighbor list (short range forces)
coulombtype	    = PME		    ; Treatment of long range electrostatic interactions
rcoulomb	    = 1.2		    ; long range electrostatic cut-off
vdwtype         = cutoff
vdw-modifier    = force-switch
rvdw-switch     = 1.0
rvdw		    = 1.2		    ; long range Van der Waals cut-off
pbc             = xyz 		    ; Periodic Boundary Conditions
DispCorr        = no

I have tried reducing the time step (emstep), using other integrator method like cg and l-bfgs but to no avail.

Any help will be greatly appreciated.

Regards,
Hemant

2

What Fmax value do you reach, and what atom is that force acting upon? What is going on around that particular atom?

Beyond that, you have to split things up to diagnose - does your ligand minimize successfully in vacuo? The protein? Complex in vacuo? Doing these assessments step by step will tell you where the issue is.

3

I forgot to mention that for most of these systems, the charmm36-feb2021 worked fine.

The Fmax was of the order of 1e4.

I shall do the other studies and get back to you.

4

Getting error while minimizing the coarse grained system generated by CharmmGUI martini maker: Energy minimization has stopped, but the forces have not converged to the
requested precision Fmax < 10 (which may not be possible for your system). It
stopped because the algorithm tried to make a new step whose size was too
small, or there was no change in the energy since last step. Either way, we
regard the minimization as converged to within the available machine
precision, given your starting configuration and EM parameters.

Double precision normally gives you higher accuracy, but this is often not
needed for preparing to run molecular dynamics.
You might need to increase your constraint accuracy, or turn
off constraints altogether (set constraints = none in mdp file)

Steepest Descents converged to machine precision in 84176 steps,
but did not reach the requested Fmax < 10.
Potential Energy = -1.6181616e+07
Maximum force = 1.0857894e+03 on atom 45616
Norm of force = 4.4494028e+00

D O M A I N   D E C O M P O S I T I O N   S T A T I S T I C S

av. #atoms communicated per step for force: 2 x 260802.0
av. #atoms communicated per step for vsites: 2 x 204.7
av. #atoms communicated per step for LINCS: 2 x 383.5