protocol work turned nan after RandomLigandRotationMove

[VincenzoChen]

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?

[davidlmobley]

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?

[VincenzoChen]

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.

[davidlmobley]

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.