MobleyLab
protocol work turned nan after RandomLigandRotationMove
I have tested the t4-toluene example and it worked well. But when I use my own system , it hasn't work quite well. In this system, the ligand is greatly larger than toluene and is in the solvent but not in protein pocket. And I has not freeze any groups. The protocolWork turned nan after performing TranslationMove in NCMC show as following:
#"Iter" "Progress (%)" "Step" "alchemicalLambda" "protocolWork" "Speed (ns/day)" "Time Remaining"
ncmc: 0 5.0% 25 0.05 39.08851538888597 0 --
ncmc: 0 10.0% 50 0.1 70.96068947520838 26.7 0:05
ncmc: 0 15.0% 75 0.15 94.11311782093316 28.2 0:05
ncmc: 0 20.0% 100 0.2 108.8464813136671 26.5 0:05
ncmc: 0 25.0% 125 0.25 108.8464813136671 26.5 0:04
ncmc: 0 30.0% 150 0.3 108.9467082762027 26.4 0:04
ncmc: 0 35.0% 175 0.35 108.9467082762027 26.2 0:04
ncmc: 0 40.0% 200 0.4 108.9467082762027 25.8 0:04
ncmc: 0 45.0% 225 0.45 108.8464813136671 25.9 0:03
ncmc: 0 50.0% 250 0.5 109.04693523873831 22.5 0:03
Performing RandomLigandRotationMove...
ncmc: 0 55.0% 275 0.55 nan 16.8 0:04
ncmc: 0 60.0% 300 0.6 nan 13.6 0:05
ncmc: 0 65.0% 325 0.65 nan 11.8 0:05
ncmc: 0 70.0% 350 0.7 nan 10.8 0:04
ncmc: 0 75.0% 375 0.75 nan 10.1 0:04
ncmc: 0 80.0% 400 0.8 nan 9.52 0:03
ncmc: 0 85.0% 425 0.85 nan 9.08 0:02
ncmc: 0 90.0% 450 0.9 nan 8.73 0:01
ncmc: 0 95.0% 475 0.95 nan 8.45 0:01
ERROR: [simulation._stepNCMC] Particle coordinate is nan
So I wander how this phenomenon comes into being. Maybe it is the clash between ligand and solvent that cause this problem?
This is a good question and I'm not sure the answer. You're saying that you're doing this in solvent, with no protein around? Would you be able to share a 2D structure or SMILES string for your ligand?
There is a protein and ligand in the system, but the ligand is in the solvent. The 2D structure of ligand are shown in picture.
OK, it looks like you're going to get extremely large energies from this for multiple reasons: (a) those charged groups are going to have very large interaction energies with their environment; (b) this is so large and flexible that almost any rigid-body rotation of it in a binding site will result in steric clashes so severe that BLUES won't be able to recover.
I think this is out of the domain of applicability of the current versions of BLUES.