units.angstroms)
complex_coordinates[1, 0] = 10.0 * units.angstroms
# Create temporary directory for testing.
import tempfile
output_directory = tempfile.mkdtemp()
# Initialize YANK object.
from yank import Yank
yank = Yank(receptor=receptor_system,
ligand=ligand_system,
complex_coordinates=[complex_coordinates],
output_directory=output_directory)
yank.solvent_protocol = yank.vacuum_protocol
yank.complex_protocol = yank.vacuum_protocol
yank.restraint_type = 'flat-bottom'
yank.temperature = temperature
yank.niterations = 100
yank.platform = openmm.Platform.getPlatformByName("Reference")
# Run the simulation.
yank.run()
#
# Analyze the data.
#
results = yank.analyze()
# TODO: Check results against analytical results.
import simtk.unit as units
complex_coordinates = units.Quantity(numpy.zeros([2,3], numpy.float64), units.angstroms)
complex_coordinates[1,0] = 10.0 * units.angstroms
# Create temporary directory for testing.
import tempfile
output_directory = tempfile.mkdtemp()
# Initialize YANK object.
from yank import Yank
yank = Yank(receptor=receptor_system, ligand=ligand_system, complex_coordinates=[complex_coordinates], output_directory=output_directory)
yank.solvent_protocol = yank.vacuum_protocol
yank.complex_protocol = yank.vacuum_protocol
yank.restraint_type = 'flat-bottom'
yank.temperature = temperature
yank.niterations = 100
yank.platform = openmm.Platform.getPlatformByName("Reference")
# Run the simulation.
yank.run()
#
# Analyze the data.
#
results = yank.analyze()
# TODO: Check results against analytical results.
def notest_LennardJonesPair(box_width_nsigma=6.0):
"""
Compute binding free energy of two Lennard-Jones particles and compare to numerical result.
Parameters
----------
box_width_nsigma : float, optional, default=6.0
Box width is set to this multiple of Lennard-Jones sigma.
"""
NSIGMA_MAX = 6.0 # number of standard errors tolerated for success
# Create Lennard-Jones pair.
thermodynamic_state = ThermodynamicState(temperature=300.0*unit.kelvin)
kT = kB * thermodynamic_state.temperature
sigma = 3.5 * unit.angstroms
epsilon = 6.0 * kT
test = testsystems.LennardJonesPair(sigma=sigma, epsilon=epsilon)
system, positions = test.system, test.positions
binding_free_energy = test.get_binding_free_energy(thermodynamic_state)
# Create temporary directory for testing.
import tempfile
store_dir = tempfile.mkdtemp()
# Initialize YANK object.
options = dict()
options['restraint_type'] = None
options['number_of_iterations'] = 10
options['platform'] = openmm.Platform.getPlatformByName("Reference") # use Reference platform for speed
options['mc_rotation'] = False
options['mc_displacement'] = True
options['mc_displacement_sigma'] = 1.0 * unit.nanometer
options['timestep'] = 2 * unit.femtoseconds
options['nsteps_per_iteration'] = 50
# Override receptor mass to keep it stationary.
#system.setParticleMass(0, 0)
# Override box vectors.
box_edge = 6*sigma
a = unit.Quantity((box_edge, 0 * unit.angstrom, 0 * unit.angstrom))
b = unit.Quantity((0 * unit.angstrom, box_edge, 0 * unit.angstrom))
c = unit.Quantity((0 * unit.angstrom, 0 * unit.angstrom, box_edge))
system.setDefaultPeriodicBoxVectors(a, b, c)
# Override positions
positions[0,:] = box_edge/2
positions[1,:] = box_edge/4
phase = 'complex-explicit'
# Alchemical protocol.
from yank.alchemy import AlchemicalState
alchemical_states = list()
lambda_values = [0.0, 0.25, 0.50, 0.75, 1.0]
for lambda_value in lambda_values:
alchemical_state = AlchemicalState()
alchemical_state['lambda_electrostatics'] = lambda_value
alchemical_state['lambda_sterics'] = lambda_value
alchemical_states.append(alchemical_state)
protocols = dict()
protocols[phase] = alchemical_states
# Create phases.
systems = { phase : system }
positions = { phase : positions }
phases = [phase]
atom_indices = { 'complex-explicit' : { 'ligand' : [1] } }
# Create new simulation.
yank = Yank(store_dir)
yank.create(phases, systems, positions, atom_indices, thermodynamic_state, options=options, protocols=protocols)
# Run the simulation.
yank.run()
# Analyze the data.
results = yank.analyze()
standard_state_correction = results[phase]['standard_state_correction']
Delta_f = results[phase]['Delta_f_ij'][0,1] - standard_state_correction
dDelta_f = results[phase]['dDelta_f_ij'][0,1]
nsigma = abs(binding_free_energy/kT - Delta_f) / dDelta_f
# Check results against analytical results.
# TODO: Incorporate standard state correction
output = "\n"
output += "Analytical binding free energy : %10.5f +- %10.5f kT\n" % (binding_free_energy / kT, 0)
output += "Computed binding free energy (with standard state correction) : %10.5f +- %10.5f kT (nsigma = %3.1f)\n" % (Delta_f, dDelta_f, nsigma)
output += "Computed binding free energy (without standard state correction): %10.5f +- %10.5f kT (nsigma = %3.1f)\n" % (Delta_f + standard_state_correction, dDelta_f, nsigma)
output += "Standard state correction alone : %10.5f kT\n" % (standard_state_correction)
print output
#if (nsigma > NSIGMA_MAX):
# output += "\n"
# output += "Computed binding free energy differs from true binding free energy.\n"
# raise Exception(output)
return [Delta_f, dDelta_f]
def notest_LennardJonesPair(box_width_nsigma=6.0):
"""
Compute binding free energy of two Lennard-Jones particles and compare to numerical result.
Parameters
----------
box_width_nsigma : float, optional, default=6.0
Box width is set to this multiple of Lennard-Jones sigma.
"""
NSIGMA_MAX = 6.0 # number of standard errors tolerated for success
# Create Lennard-Jones pair.
thermodynamic_state = ThermodynamicState(temperature=300.0 * unit.kelvin)
kT = kB * thermodynamic_state.temperature
sigma = 3.5 * unit.angstroms
epsilon = 6.0 * kT
test = testsystems.LennardJonesPair(sigma=sigma, epsilon=epsilon)
system, positions = test.system, test.positions
binding_free_energy = test.get_binding_free_energy(thermodynamic_state)
# Create temporary directory for testing.
import tempfile
store_dir = tempfile.mkdtemp()
# Initialize YANK object.
options = dict()
options['restraint_type'] = None
options['number_of_iterations'] = 10
options['platform'] = openmm.Platform.getPlatformByName(
"Reference") # use Reference platform for speed
options['mc_rotation'] = False
options['mc_displacement'] = True
options['mc_displacement_sigma'] = 1.0 * unit.nanometer
options['timestep'] = 2 * unit.femtoseconds
options['nsteps_per_iteration'] = 50
# Override receptor mass to keep it stationary.
#system.setParticleMass(0, 0)
# Override box vectors.
box_edge = 6 * sigma
a = unit.Quantity((box_edge, 0 * unit.angstrom, 0 * unit.angstrom))
b = unit.Quantity((0 * unit.angstrom, box_edge, 0 * unit.angstrom))
c = unit.Quantity((0 * unit.angstrom, 0 * unit.angstrom, box_edge))
system.setDefaultPeriodicBoxVectors(a, b, c)
# Override positions
positions[0, :] = box_edge / 2
positions[1, :] = box_edge / 4
phase = 'complex-explicit'
# Alchemical protocol.
from yank.alchemy import AlchemicalState
alchemical_states = list()
lambda_values = [0.0, 0.25, 0.50, 0.75, 1.0]
for lambda_value in lambda_values:
alchemical_state = AlchemicalState()
alchemical_state['lambda_electrostatics'] = lambda_value
alchemical_state['lambda_sterics'] = lambda_value
alchemical_states.append(alchemical_state)
protocols = dict()
protocols[phase] = alchemical_states
# Create phases.
systems = {phase: system}
positions = {phase: positions}
phases = [phase]
atom_indices = {'complex-explicit': {'ligand': [1]}}
# Create new simulation.
yank = Yank(store_dir, **options)
yank.create(phases,
systems,
positions,
atom_indices,
thermodynamic_state,
protocols=protocols)
# Run the simulation.
yank.run()
# Analyze the data.
results = yank.analyze()
standard_state_correction = results[phase]['standard_state_correction']
Delta_f = results[phase]['Delta_f_ij'][0, 1] - standard_state_correction
dDelta_f = results[phase]['dDelta_f_ij'][0, 1]
nsigma = abs(binding_free_energy / kT - Delta_f) / dDelta_f
# Check results against analytical results.
# TODO: Incorporate standard state correction
output = "\n"
output += "Analytical binding free energy : %10.5f +- %10.5f kT\n" % (
binding_free_energy / kT, 0)
output += "Computed binding free energy (with standard state correction) : %10.5f +- %10.5f kT (nsigma = %3.1f)\n" % (
Delta_f, dDelta_f, nsigma)
output += "Computed binding free energy (without standard state correction): %10.5f +- %10.5f kT (nsigma = %3.1f)\n" % (
Delta_f + standard_state_correction, dDelta_f, nsigma)
output += "Standard state correction alone : %10.5f kT\n" % (
standard_state_correction)
print output
#if (nsigma > NSIGMA_MAX):
# output += "\n"
# output += "Computed binding free energy differs from true binding free energy.\n"
# raise Exception(output)
return [Delta_f, dDelta_f]
