[gmx-users] How to fix restraints in free energy calculation?

[Sadaf Rani]

Dear Gromacs users
I am doing a free energy calculation of the protein-ligand complex. During
decoupling of the ligand vdw forces from protein, I have selected 21
different lambda windows between 0-1.
I have put distance angle and dihedral restraints to keep the ligand in its
position but in some of my lamda windows, the residue restrained with
ligand crashes and generates different PDB structures. It crashes in lambda
windows 0,1,2,4,8,9,11,12,13,17,18 however in windows 3,5,6,10, 14,15,19,20
it works well.
My restraint section in topology is as below:-

; distance restraints
[ bonds ]
;    i     j  type     r0A     r1A     r2A    fcA    r0B     r1B     r2B
 fcB
  3437  7908    10     0.474   0.474   10.0   0.0    0.474   0.474   10.0
4184.000

[ angle_restraints ]
;   ai    aj    ak    al  type    thA      fcA    multA  thB      fcB
 multB
  3437  7908  7905  7908       1    110.00   0.0    1     110.00    41.840
  1
  7908  3437  3439  3437       1    152.5    0.0    1     152.5     41.840
  1

[ dihedral_restraints ]
;   ai    aj    ak    al   type    phiA    dphiA  fcA    phiB      dphiB
 fcB
  7905  7908  3437  3439     1    140.19   0.0    0.0    140.19    0.0
 41.840
  7909  7908  3437  3439     1    -167.75  0.0    0.0    -69.05    0.0
 41.840
  7909  7908  3437  3433     1    -172.77  0.0    0.0   -172.77    0.0
 41.840


Can anyone please suggest me how should I fix this? or where I am doing
wrong?
I will be really grateful.

Thanks

Sadaf Rani
P.hD. visiting scholar
Lancaster University
Uk