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openmmtools.mcmc - Potential energy is NaN after 0 attempts of integration with move LangevinSplittingDynamicsMove Attempting a restart... #82

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agreen69 opened this issue Oct 10, 2018 · 4 comments
Open

openmmtools.mcmc - Potential energy is NaN after 0 attempts of integration with move LangevinSplittingDynamicsMove Attempting a restart... #82

agreen69 opened this issue Oct 10, 2018 · 4 comments

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@agreen69
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For the Abl-imatinib example,

I get the following error and a seg fault after minimization with FIRE:

2018-10-10 15:10:01,246: Running _propagate_replica serially.
2018-10-10 15:10:13,854: WARNING - openmmtools.mcmc - Potential energy is NaN after 0 attempts of integration with move LangevinSplittingDynamicsMove Attempting a restart...
2018-10-10 15:10:22,762: WARNING - openmmtools.mcmc - Potential energy is NaN after 1 attempts of integration with move LangevinSplittingDynamicsMove Attempting a restart...
2018-10-10 15:10:31,666: WARNING - openmmtools.mcmc - Potential energy is NaN after 2 attempts of integration with move LangevinSplittingDynamicsMove Attempting a restart...
2018-10-10 15:10:40,587: WARNING - openmmtools.mcmc - Potential energy is NaN after 3 attempts of integration with move LangevinSplittingDynamicsMove Attempting a restart...
2018-10-10 15:10:49,501: WARNING - openmmtools.mcmc - Potential energy is NaN after 4 attempts of integration with move LangevinSplittingDynamicsMove Attempting a restart...
2018-10-10 15:10:58,428: ERROR - openmmtools.mcmc - Potential energy is NaN after 5 attempts of integration with move LangevinSplittingDynamicsMove Trying to reinitialize Context as a last-resort restart attempt...
Segmentation fault

Here is my input file.

options:
minimize: no
verbose: yes
default_number_of_iterations: 250
default_nsteps_per_iteration: 2500
temperature: 300kelvin
default_timestep: 2.0femtoseconds
platform: fastest
output_dir: implicit
resume_setup: no
resume_simulation: no

molecules:
Abl:
filepath: input/2HYY-pdbfixer.pdb
STI:
filepath: input/STI02.mol2
antechamber:
charge_method: null

solvents:
GBSA:
nonbonded_method: NoCutoff # Main definition of the nonbonded method
implicit_solvent: OBC2 # Onufriev-Bashford-Case GBSA model, name is related to Implicit solvents in OpenMM

systems:
Abl-STI:
receptor: Abl
ligand: STI
solvent: GBSA
leap:
parameters: [leaprc.protein.ff14SB, leaprc.gaff2, leaprc.water.tip3p]

protocols:
absolute-binding:
complex:
alchemical_path:
lambda_restraints: [0.00, 0.25, 0.50, 0.75, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.000, 1.00, 1.000, 1.00, 1.00]
lambda_electrostatics: [1.00, 1.00, 1.00, 1.00, 1.00, 0.95, 0.90, 0.85, 0.80, 0.75, 0.70, 0.65, 0.60, 0.55, 0.50, 0.45, 0.40, 0.35, 0.30, 0.25, 0.20, 0.15, 0.10, 0.05, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.000, 0.00, 0.000, 0.00, 0.00]
lambda_sterics: [1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 0.95, 0.90, 0.85, 0.80, 0.75, 0.70, 0.65, 0.60, 0.55, 0.50, 0.45, 0.40, 0.35, 0.30, 0.25, 0.20, 0.15, 0.10, 0.075, 0.05, 0.025, 0.01, 0.00]
solvent:
alchemical_path:
lambda_electrostatics: [1.00, 0.90, 0.80, 0.70, 0.60, 0.50, 0.40, 0.30, 0.20, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00, 0.00]
lambda_sterics: [1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 0.90, 0.80, 0.70, 0.60, 0.50, 0.40, 0.30, 0.20, 0.10, 0.00]

experiments:
system: Abl-STI
protocol: absolute-binding
restraint:
type: Boresch

I modified and removed the Epik and OpenEye sections since I do not have either one of those programs installed on my system.

Any idea on what could be the problem? Is it an issue with MCMC samplers?

I am using Yank 0.23.4

YANK Selftest

Yank Version 0.23.4

Available OpenMM platforms:
0 Reference
1 CPU
2 CUDA
3 OpenCL

Valid OpenEye install not found
Not required, but please check install if you expected it

Checking GPU Computed Mode (if present)...
Found 4 NVIDIA GPUs in the following modes: [Default, Default, Default, Default]
These should all be in shared/Default mode for YANK to use them
YANK Selftest complete.
Thank you for using YANK!
@andrrizzi
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In the YAML script above you have minimize: no. I'd try to set it to yes as this looks like a steric clash to me. Note that we've released other 3 bugfix releases since YANK 0.23.4, so I'd update to the latest version (0.23.7).

@agreen69
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Same error using FIRE to minimize and with version 0.23.7.

2018-10-10 17:21:12,140: Using FIRE: tolerance 1.0 kJ/(nm mol) max_iterations 1000
2018-10-10 17:21:20,153: Replica 47/48: final energy 92116.400kT
2018-10-10 17:21:22,457: Replica 48/48: initial energy 92117.900kT
2018-10-10 17:21:22,458: Using FIRE: tolerance 1.0 kJ/(nm mol) max_iterations 1000
2018-10-10 17:21:30,442: Replica 48/48: final energy 92117.900kT
2018-10-10 17:21:30,528: Single node: executing <bound method MultiStateReporter.write_sampler_states of <yank.multistate.multistatereporter.MultiStateReporter object at 0x2ac036075668>>
2018-10-10 17:21:31,826: Storing sampler states took 1.298s
2018-10-10 17:21:31,827: Minimizing all replicas took 511.455s
2018-10-10 17:21:31,829: Running _compute_replica_energies serially.
2018-10-10 17:21:39,175: Computing energy matrix took 7.347s
2018-10-10 17:21:39,176: Single node: executing <bound method MultiStateReporter.write_energies of <yank.multistate.multistatereporter.MultiStateReporter object at 0x2ac036075668>>
2018-10-10 17:21:39,179: ********************************************************************************
2018-10-10 17:21:39,179: Iteration 1/250
2018-10-10 17:21:39,179: ********************************************************************************
2018-10-10 17:21:39,180: Single node: executing <function ReplicaExchangeSampler._mix_replicas at 0x2ac0340161e0>
2018-10-10 17:21:39,180: Mixing replicas...
2018-10-10 17:21:39,473: Mixing of replicas took 0.293s
2018-10-10 17:21:39,473: Accepted 10616832/10616832 attempted swaps (100.0%)
2018-10-10 17:21:39,473: Propagating all replicas...
2018-10-10 17:21:39,474: Running _propagate_replica serially.
2018-10-10 17:21:50,507: WARNING - openmmtools.mcmc - Potential energy is NaN after 0 attempts of integration with move LangevinSplittingDynamicsMove Attempting a restart...
2018-10-10 17:21:59,366: WARNING - openmmtools.mcmc - Potential energy is NaN after 1 attempts of integration with move LangevinSplittingDynamicsMove Attempting a restart...
2018-10-10 17:22:08,233: WARNING - openmmtools.mcmc - Potential energy is NaN after 2 attempts of integration with move LangevinSplittingDynamicsMove Attempting a restart...
2018-10-10 17:22:17,205: WARNING - openmmtools.mcmc - Potential energy is NaN after 3 attempts of integration with move LangevinSplittingDynamicsMove Attempting a restart...
2018-10-10 17:22:26,070: WARNING - openmmtools.mcmc - Potential energy is NaN after 4 attempts of integration with move LangevinSplittingDynamicsMove Attempting a restart...
2018-10-10 17:22:34,963: ERROR - openmmtools.mcmc - Potential energy is NaN after 5 attempts of integration with move LangevinSplittingDynamicsMove Trying to reinitialize Context as a last-resort restart attempt...
Segmentation fault

And there also appears to be a compatibility issue between numpy and yank 0.23.7:
yank selftest
/home/a12/miniconda3/lib/python3.5/importlib/_bootstrap.py:222: RuntimeWarning: numpy.dtype size changed, may indicate binary incompatibility. Expected 96, got 88
return f(*args, **kwds)
/home/a12/miniconda3/lib/python3.5/importlib/_bootstrap.py:222: RuntimeWarning: numpy.dtype size changed, may indicate binary incompatibility. Expected 96, got 88
return f(*args, **kwds)
/home/a12/miniconda3/lib/python3.5/importlib/_bootstrap.py:222: RuntimeWarning: numpy.dtype size changed, may indicate binary incompatibility. Expected 96, got 88
return f(*args, **kwds)

YANK Selftest

Yank Version 0.23.7

Available OpenMM platforms:
0 Reference
1 CPU
2 CUDA
3 OpenCL

Valid OpenEye install not found
Not required, but please check install if you expected it

Checking GPU Computed Mode (if present)...
Found 4 NVIDIA GPUs in the following modes: [Default, Default, Default, Default]
These should all be in shared/Default mode for YANK to use them
YANK Selftest complete.
Thank you for using YANK!

This warning is with numpy 1.14 and 1.15.

@andrrizzi
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The potential energies of your initial structures are very high (92116.400kT), and likely the minimizer is not able to resolve the clashes. I'd check the structures visually to see why the initial potential energy is so high.

@quantaosun
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I have met the same problem, has this been resolved? And anyone could provide a way to do a more proper minimization?

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@andrrizzi @agreen69 @quantaosun