Restraining two ZN position during minimization, equilibration and MD run

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1

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Please I’m new to using Gromacs, and I need help in restraining the distance between two ZN ions. The distance between the ZNs is critical, and the ligand unbinds if the distance increases. Unforunately, minimization using charm ff increases that distances. I have tried both bond and distance restraint as suggested in this forum, but have not been successful because the two ZN positions are not being identified correctly, and it gives the error shown below. In addition, I’ve included my topol.top, ZN2.itp, and a portion of the.gro file. Thanks in advance for your help and guidance.

ERROR 1 [file posre1.itp, line 6]:
Atom index (2) in position_restraints out of bounds (1-1).
This probably means that you have inserted topology section
“position_restraints”
in a part belonging to a different molecule than you intended to.
In that case move the “position_restraints” section to the right molecule
topol.top

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ZN2.itp
;; Generated by CHARMM-GUI FF-Converter
;;
;; Correspondance:
;; jul316@lehigh.edu or wonpil@lehigh.edu
;;
;; GROMACS topology file for ZN2
;;
[ moleculetype ]
; name nrexcl
ZN2 1

[ atoms ]
; nr type resnr residu atom cgnr charge mass
1 ZN 301 ZN2 ZN 1 2.000000 65.3700 ; qtot 2.000

part of my .gro file

3436 221LYS NZ 3434 6.490 4.427 4.270
3437 221LYS HZ1 3435 6.487 4.523 4.231
3438 221LYS HZ2 3436 6.571 4.420 4.336
3439 221LYS HZ3 3437 6.404 4.408 4.325
3440 221LYS C 3438 6.771 4.706 3.720
3441 221LYS OT1 3439 6.760 4.743 3.601
3442 221LYS OT2 3440 6.879 4.713 3.785
3443 222ZN2 ZN 3441 4.334 4.618 3.882
3444 223ZN2 ZN 3442 4.169 4.707 3.335
3445 2243R9 O1 3443 4.681 4.599 3.366
3446 2243R9 N 3444 4.366 4.812 3.357
3447 2243R9 C1 3445 4.546 4.633 3.378
3448 2243R9 O2 3446 4.472 4.564 3.444
3449 2243R9 C2 3447 4.500 4.764 3.306

2

Position restraints are applied based on topological numbering. Your .itp file specifies one atom, so the only valid number in a [position_restraints] directive is 1. The [molecules] directive subsequently indicates two copies of this species, so any restraint is applied to both ions simultaneously.

3

Thanks, Jalemkul, for your response. I used 1, and I figured I had to increase the values of fcx, fcy, and fcz to 100,000 before it eventually restrained the position of the zinc ions during minimization and equilibration. Unfortunately, this didn’t work for the MD run as the distances increased drastically. Please, should I keep increasing the values, or is there something I’m doing wrong?
Also, when I tried to use distant restraint for the ZN ions, both inputs below gave me errors. Also, am I using it correctly?
[ bonds ]
1 1 6 3.5 1000
&
[ bonds ]
1 2 6 3.5 1000
Thanks once again for your anticipated response.

4

If the ions are repelling from one another, that suggests a more fundamental problem. Binding sites with multiple metals will require different treatment of side chains, usually Cys which should be anionic. If that is not the case in your topology, you need to regenerate it with the appropriate Cys type (CYM for Cys-). Then the Zn2+ coordination should be better maintained. Otherwise, you will need lots of distance restraints to preserve the coordination geometry, not position restraints.