LightDock setup failure - Found wrong coefficient on calculating poses with restraints

[lightdock]

LightDock setup failure - Found wrong coefficient on calculating poses with restraints

[kaze33]

Thanks a lot for the clarification and the steps to solve the issue, it worked perfectly when I switched ligand and receptor!

Best,
Eloi

[brianjimenez]

Hi Eloi,
Thank you for using LightDock. We had a quick look to the issue. The raised error Found wrong coefficient on calculating poses with restraints is a safety check for degenerate corner cases when trying to preorient ligand poses against simulated dummy residues over the receptor surface. Depending on the ligand shape and the initial ligand translation within the swarm, some preorienting might not be possible. To avoid this situation, the simplest solution is to swap receptor and ligand. Indeed, we think that has some advantages in this scenario as many less swarms are going to be generated and thus simulation time will be decreased.

Please follow these instructions to make this simulation setup working:

1. Remove all HETATM from both PDB structures.
2. Swap L -> R in restraints file:

R A.GLY.27
R A.ALA.28
R A.THR.29
R A.SER.30
R A.ASN.31
R A.ILE.32
R A.SER.33
R A.SER.53
R A.ARG.54
R A.ALA.55
R A.GLU.56
R A.SER.57
R A.ARG.58
R A.PRO.59
R A.PRO.102
R A.LEU.103
R A.VAL.104
R A.ARG.105
R A.HIS.106
R A.LYS.107

3. Re-run the setup:

lightdock3_setup.py EM1noH.pdb HER2noH.pdb 400 200 -anm --noxt --noh -rst restraintsEM1.list

Setup now completes successfully:

(with the bonus of only simulating 56 swarms instead of 400!). This protocol of using only restraints in the ligand side was developed for our new research using explicit membrane representation which will be available very soon.