def test_parameters():
"""Test Yank parameters initialization."""
# Check that both Yank and Repex parameters are accepted
Yank(store_directory='test',
restraint_type='harmonic',
nsteps_per_iteration=1)
def driver():
# Initialize command-line argument parser.
verbose = True
usage = """
USAGE
%prog --ligand_prmtop PRMTOP --receptor_prmtop PRMTOP { {--ligand_crd CRD | --ligand_mol2 MOL2} {--receptor_crd CRD | --receptor_pdb PDB} | {--complex_crd CRD | --complex_pdb PDB} } [-v | --verbose] [-i | --iterations ITERATIONS] [-o | --online] [-m | --mpi] [--restraints restraint-type] [--doctests] [--randomize_ligand]
EXAMPLES
# Specify AMBER prmtop/crd files for ligand and receptor.
%prog --ligand_prmtop ligand.prmtop --receptor_prmtop receptor.prmtop --ligand_crd ligand.crd --receptor_crd receptor.crd --iterations 1000
# Specify (potentially multi-conformer) mol2 file for ligand and (potentially multi-model) PDB file for receptor.
%prog --ligand_prmtop ligand.prmtop --receptor_prmtop receptor.prmtop --ligand_mol2 ligand.mol2 --receptor_pdb receptor.pdb --iterations 1000
# Specify (potentially multi-model) PDB file for complex, along with flat-bottom restraints (instead of harmonic).
%prog --ligand_prmtop ligand.prmtop --receptor_prmtop receptor.prmtop --complex_pdb complex.pdb --iterations 1000 --restraints flat-bottom
# Specify (potentially multi-model) PDB file for complex, along with flat-bottom restraints (instead of harmonic); randomize ligand positions/orientations at start.
%prog --ligand_prmtop ligand.prmtop --receptor_prmtop receptor.prmtop --complex_pdb complex.pdb --iterations 1000 --restraints flat-bottom --randomize_ligand
NOTES
In atom ordering, receptor comes before ligand atoms.
"""
# Parse command-line arguments.
from optparse import OptionParser
parser = OptionParser(usage=usage)
parser.add_option("--ligand_mol2", dest="ligand_mol2_filename", default=None, help="ligand mol2 file (can contain multiple conformations)", metavar="LIGAND_MOL2")
parser.add_option("--receptor_pdb", dest="receptor_pdb_filename", default=None, help="receptor PDB file (can contain multiple MODELs)", metavar="RECEPTOR_PDB")
parser.add_option("--complex_pdb", dest="complex_pdb_filename", default=None, help="complex PDB file (can contain multiple MODELs)", metavar="COMPLEX_PDB")
parser.add_option("-v", "--verbose", action="store_true", dest="verbose", default=False, help="verbosity flag")
parser.add_option("-i", "--iterations", dest="niterations", default=None, help="number of iterations", metavar="ITERATIONS")
parser.add_option("-o", "--online", dest="online_analysis", default=False, help="perform online analysis")
parser.add_option("-m", "--mpi", action="store_true", dest="mpi", default=False, help="use mpi if possible")
parser.add_option("--restraints", dest="restraint_type", default=None, help="specify ligand restraint type: 'harmonic' or 'flat-bottom' (default: 'harmonic')")
parser.add_option("--output", dest="output_directory", default=None, help="specify output directory---must be unique for each calculation (default: current directory)")
parser.add_option("--doctests", action="store_true", dest="doctests", default=False, help="run doctests first (default: False)")
parser.add_option("--randomize_ligand", action="store_true", dest="randomize_ligand", default=False, help="randomize ligand positions and orientations (default: False)")
parser.add_option("--ignore_signal", action="append", dest="ignore_signals", default=[], help="signals to trap and ignore (default: None)")
parser.add_option("--platform", dest="platform", default="CPU",help="The platform to use when running simulations")
parser.add_option("--gpus_per_node", dest="gpus_per_node", type='int', default=None, help="number of GPUs per node to use for complex simulations during MPI calculations")
# Parse command-line arguments.
(options, args) = parser.parse_args()
if options.doctests:
print "Running doctests for all modules..."
import doctest
# TODO: Test all modules
import yank, oldrepex, alchemy, analyze, utils
(failure_count, test_count) = doctest.testmod(verbose=options.verbose)
if failure_count == 0:
print "All doctests pass."
sys.exit(0)
else:
print "WARNING: There were %d doctest failures." % failure_count
sys.exit(1)
# Check arguments for validity.
if not (options.ligand_mol2_filename):
parser.error("Please supply a ligand in mol2 format")
if not (options.receptor_pdb_filename):
parser.error("Please supply the receptor in pdb format")
if not (options.complex_pdb_filename):
print("Will combine ligand and receptor")
# Initialize MPI if requested.
if options.mpi:
# Initialize MPI.
try:
from mpi4py import MPI # MPI wrapper
hostname = os.uname()[1]
options.mpi = MPI.COMM_WORLD
if not MPI.COMM_WORLD.rank == 0:
options.verbose = False
MPI.COMM_WORLD.barrier()
if MPI.COMM_WORLD.rank == 0: print "Initialized MPI on %d processes." % (MPI.COMM_WORLD.size)
except Exception as e:
print e
parser.error("Could not initialize MPI.")
# Select simulation parameters.
# TODO: Allow user selection or intelligent automated selection of simulation parameters.
# NOTE: Simulation paramters are hard-coded for now.
# NOTE: Simulation parameters will be different for explicit solvent.
import simtk.openmm.app as app
nonbondedMethod = app.NoCutoff
implicitSolvent = app.OBC2
constraints = app.HBonds
removeCMMotion = False
#make ligand, receptor, complex objects
ligand = Mol2SystemBuilder(options.ligand_mol2_filename, "ligand")
receptor = BiomoleculePDBSystemBuilder(options.receptor_pdb_filename,"receptor")
complex = ComplexSystemBuilder(ligand,receptor,"complex")
# DEBUG: Write out ligand, receptor, and complex system objects.
debug = False
if debug:
def write_file(outfile, contents):
outfile = open(outfile, 'w')
outfile.write(contents)
outfile.close()
for name in ['receptor', 'ligand', 'complex']:
system = vars()[name].system
serialized_system = system.__getstate__()
filename = name + '.system.xml'
print "Writing serialized %s to %s..." % (name, filename)
write_file(filename, serialized_system)
# Initialize YANK object.
from yank import Yank
yank = Yank(receptor=receptor.system, ligand=ligand.system, complex=complex.system, complex_positions=[complex.coordinates_as_quantity], output_directory=options.output_directory, verbose=options.verbose)
# Configure YANK object with command-line parameter overrides.
if options.niterations is not None:
yank.niterations = int(options.niterations)
if options.verbose:
yank.verbose = options.verbose
if options.online_analysis:
yank.online_analysis = options.online_analysis
if options.restraint_type is not None:
yank.restraint_type = options.restraint_type
if options.randomize_ligand:
yank.randomize_ligand = True
if options.platform:
yank.platform = openmm.Platform.getPlatformByName(options.platform)
# Hard-coded cpuid:gpuid for Exxact 4xGPU nodes
# TODO: Replace this with something automated
# cpuid_gpuid_mapping = { 0:0, 1:1, 2:2, 3:3 }
#ncpus_per_node = None
# Run calculation.brbz
if options.mpi:
# Run MPI version.
yank.run_mpi(options.mpi, options.gpus_per_node)
else:
# Run serial version.
yank.run()
# Run analysis.
results = yank.analyze()
# Print/write results.
print results
def driver():
# Initialize command-line argument parser.
usage = """
USAGE
%prog --ligand_prmtop PRMTOP --receptor_prmtop PRMTOP { {--ligand_crd CRD | --ligand_mol2 MOL2} {--receptor_crd CRD | --receptor_pdb PDB} | {--complex_crd CRD | --complex_pdb PDB} } [-v | --verbose] [-i | --iterations ITERATIONS] [-o | --online] [-m | --mpi] [--restraints restraint-type] [--doctests] [--randomize_ligand]
EXAMPLES
# Specify AMBER prmtop/crd files for ligand and receptor.
%prog --ligand_prmtop ligand.prmtop --receptor_prmtop receptor.prmtop --ligand_crd ligand.crd --receptor_crd receptor.crd --iterations 1000
# Specify (potentially multi-conformer) mol2 file for ligand and (potentially multi-model) PDB file for receptor.
%prog --ligand_prmtop ligand.prmtop --receptor_prmtop receptor.prmtop --ligand_mol2 ligand.mol2 --receptor_pdb receptor.pdb --iterations 1000
# Specify (potentially multi-model) PDB file for complex, along with flat-bottom restraints (instead of harmonic).
%prog --ligand_prmtop ligand.prmtop --receptor_prmtop receptor.prmtop --complex_pdb complex.pdb --iterations 1000 --restraints flat-bottom
# Specify (potentially multi-model) PDB file for complex, along with flat-bottom restraints (instead of harmonic); randomize ligand positions/orientations at start.
%prog --ligand_prmtop ligand.prmtop --receptor_prmtop receptor.prmtop --complex_pdb complex.pdb --iterations 1000 --restraints flat-bottom --randomize_ligand
NOTES
In atom ordering, receptor comes before ligand atoms.
"""
# Parse command-line arguments.
from optparse import OptionParser
parser = OptionParser(usage=usage)
parser.add_option("--ligand_prmtop", dest="ligand_prmtop_filename", default=None, help="ligand Amber parameter file", metavar="LIGAND_PRMTOP")
parser.add_option("--receptor_prmtop", dest="receptor_prmtop_filename", default=None, help="receptor Amber parameter file", metavar="RECEPTOR_PRMTOP")
parser.add_option("--ligand_crd", dest="ligand_crd_filename", default=None, help="ligand Amber crd file", metavar="LIGAND_CRD")
parser.add_option("--receptor_crd", dest="receptor_crd_filename", default=None, help="receptor Amber crd file", metavar="RECEPTOR_CRD")
parser.add_option("--ligand_mol2", dest="ligand_mol2_filename", default=None, help="ligand mol2 file (can contain multiple conformations)", metavar="LIGAND_MOL2")
parser.add_option("--receptor_pdb", dest="receptor_pdb_filename", default=None, help="receptor PDB file (can contain multiple MODELs)", metavar="RECEPTOR_PDB")
parser.add_option("--complex_prmtop", dest="complex_prmtop_filename", default=None, help="complex Amber parameter file", metavar="COMPLEX_PRMTOP")
parser.add_option("--complex_crd", dest="complex_crd_filename", default=None, help="complex Amber crd file", metavar="COMPLEX_CRD")
parser.add_option("--complex_pdb", dest="complex_pdb_filename", default=None, help="complex PDB file (can contain multiple MODELs)", metavar="COMPLEX_PDB")
parser.add_option("-v", "--verbose", action="store_true", dest="verbose", default=False, help="verbosity flag")
parser.add_option("-i", "--iterations", dest="niterations", default=None, help="number of iterations", metavar="ITERATIONS")
parser.add_option("-o", "--online", dest="online_analysis", default=False, help="perform online analysis")
parser.add_option("-m", "--mpi", action="store_true", dest="mpi", default=False, help="use mpi if possible")
parser.add_option("--restraints", dest="restraint_type", default=None, help="specify ligand restraint type: 'harmonic' or 'flat-bottom' (default: 'harmonic')")
parser.add_option("--output", dest="output_directory", default=None, help="specify output directory---must be unique for each calculation (default: current directory)")
parser.add_option("--doctests", action="store_true", dest="doctests", default=False, help="run doctests first (default: False)")
parser.add_option("--randomize_ligand", action="store_true", dest="randomize_ligand", default=False, help="randomize ligand positions and orientations (default: False)")
parser.add_option("--ignore_signal", action="append", dest="ignore_signals", default=[], help="signals to trap and ignore (default: None)")
# Parse command-line arguments.
(options, args) = parser.parse_args()
if options.doctests:
print "Running doctests for all modules..."
import doctest
# TODO: Test all modules
import yank, oldrepex, alchemy, analyze, utils
(failure_count, test_count) = doctest.testmod(verbose=options.verbose)
if failure_count == 0:
print "All doctests pass."
sys.exit(0)
else:
print "WARNING: There were %d doctest failures." % failure_count
sys.exit(1)
# Check arguments for validity.
if not (options.ligand_prmtop_filename and options.receptor_prmtop_filename):
parser.error("ligand and receptor prmtop files must be specified")
if not (bool(options.ligand_mol2_filename) ^ bool(options.ligand_crd_filename) ^ bool(options.complex_pdb_filename) ^ bool(options.complex_crd_filename)):
parser.error("Ligand coordinates must be specified through only one of --ligand_crd, --ligand_mol2, --complex_crd, or --complex_pdb.")
if not (bool(options.receptor_pdb_filename) ^ bool(options.receptor_crd_filename) ^ bool(options.complex_pdb_filename) ^ bool(options.complex_crd_filename)):
parser.error("Receptor coordinates must be specified through only one of --receptor_crd, --receptor_pdb, --complex_crd, or --complex_pdb.")
if not (options.complex_prmtop_filename):
parser.error("Please specify --complex_prmtop [complex_prmtop_filename] argument.")
# Initialize MPI if requested.
if options.mpi:
# Initialize MPI.
try:
from mpi4py import MPI # MPI wrapper
hostname = os.uname()[1]
options.mpi = MPI.COMM_WORLD
if not MPI.COMM_WORLD.rank == 0:
options.verbose = False
MPI.COMM_WORLD.barrier()
if MPI.COMM_WORLD.rank == 0: print "Initialized MPI on %d processes." % (MPI.COMM_WORLD.size)
except Exception as e:
print e
parser.error("Could not initialize MPI.")
# Select simulation parameters.
# TODO: Allow user selection or intelligent automated selection of simulation parameters.
# NOTE: Simulation paramters are hard-coded for now.
# NOTE: Simulation parameters will be different for explicit solvent.
import simtk.openmm.app as app
nonbondedMethod = app.NoCutoff
implicitSolvent = app.OBC2
constraints = app.HBonds
removeCMMotion = False
# Create System objects for ligand and receptor.
ligand_system = app.AmberPrmtopFile(options.ligand_prmtop_filename).createSystem(nonbondedMethod=nonbondedMethod, implicitSolvent=implicitSolvent, constraints=constraints, removeCMMotion=removeCMMotion)
receptor_system = app.AmberPrmtopFile(options.receptor_prmtop_filename).createSystem(nonbondedMethod=nonbondedMethod, implicitSolvent=implicitSolvent, constraints=constraints, removeCMMotion=removeCMMotion)
complex_system = app.AmberPrmtopFile(options.complex_prmtop_filename).createSystem(nonbondedMethod=nonbondedMethod, implicitSolvent=implicitSolvent, constraints=constraints, removeCMMotion=removeCMMotion)
# Determine number of atoms for each system.
natoms_receptor = receptor_system.getNumParticles()
natoms_ligand = ligand_system.getNumParticles()
natoms_complex = complex_system.getNumParticles()
if (natoms_complex != natoms_ligand + natoms_receptor):
raise Exception("Number of complex atoms must equal sum of ligand and receptor atoms.")
# Read ligand and receptor coordinates.
ligand_coordinates = list()
receptor_coordinates = list()
complex_coordinates = list()
if (options.complex_crd_filename or options.complex_pdb_filename):
# Read coordinates for whole complex.
if options.complex_crd_filename:
coordinates = read_amber_crd(options.complex_crd_filename, natoms_complex, options.verbose)
complex_coordinates.append(coordinates)
else:
try:
coordinates_list = read_openeye_crd(options.complex_pdb_filename, natoms_complex, options.verbose)
except:
coordinates_list = read_pdb_crd(options.complex_pdb_filename, natoms_complex, options.verbose)
complex_coordinates += coordinates_list
elif options.ligand_crd_filename:
coordinates = read_amber_crd(options.ligand_crd_filename, natoms_ligand, options.verbose)
coordinates = units.Quantity(numpy.array(coordinates / coordinates.unit), coordinates.unit)
ligand_coordinates.append(coordinates)
elif options.ligand_mol2_filename:
coordinates_list = read_openeye_crd(options.ligand_mol2_filename, natoms_ligand, options.verbose)
ligand_coordinates += coordinates_list
elif options.receptor_crd_filename:
coordinates = read_amber_crd(options.receptor_crd_filename, natoms_receptor, options.verbose)
coordinates = units.Quantity(numpy.array(coordinates / coordinates.unit), coordinates.unit)
receptor_coordinates.append(coordinates)
elif options.receptor_pdb_filename:
try:
coordinates_list = read_openeye_crd(options.receptor_pdb_filename, natoms_receptor, options.verbose)
except:
coordinates_list = read_pdb_crd(options.receptor_pdb_filename, natoms_receptor, options.verbose)
receptor_coordinates += coordinates_list
# Assemble complex coordinates if we haven't read any.
if len(complex_coordinates)==0:
for x in receptor_coordinates:
for y in ligand_coordinates:
z = units.Quantity(numpy.zeros([natoms_complex,3]), units.angstroms)
z[0:natoms_receptor,:] = x[:,:]
z[natoms_receptor:natoms_complex,:] = y[:,:]
complex_coordinates.append(z)
# Initialize YANK object.
from yank import Yank
yank = Yank(receptor=receptor_system, ligand=ligand_system, complex=complex_system, complex_coordinates=complex_coordinates, output_directory=options.output_directory, verbose=options.verbose)
# Configure YANK object with command-line parameter overrides.
if options.niterations is not None:
yank.niterations = int(options.niterations)
if options.verbose:
yank.verbose = options.verbose
if options.online_analysis:
yank.online_analysis = options.online_analysis
if options.restraint_type is not None:
yank.restraint_type = options.restraint_type
if options.randomize_ligand:
yank.randomize_ligand = True
# Hard-coded cpuid:gpuid for Exxact 4xGPU nodes
# TODO: Replace this with something automated
cpuid_gpuid_mapping = { 0:0, 1:1, 2:2, 3:3 }
ncpus_per_node = None
# Run calculation.
if options.mpi:
# Run MPI version.
yank.run_mpi(options.mpi, cpuid_gpuid_mapping=cpuid_gpuid_mapping, ncpus_per_node=ncpus_per_node)
else:
# Run serial version.
yank.run()
# Run analysis.
results = yank.analyze()
# Print/write results.
print results
#receptor_system.addForce(force)
# Create complex coordinates.
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.
#
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]
#force.addGlobalParameter('Kext', kT / sigma**2)
#force.addParticle(0, [])
#receptor_system.addForce(force)
# Create complex coordinates.
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()
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]
def test_unknown_parameters():
"""Test whether Yank raises exception on wrong initialization."""
Yank(store_directory='test', wrong_parameter=False)
def driver():
# Initialize command-line argument parser.
verbose = True
usage = """
USAGE
%prog --ligand_prmtop PRMTOP --receptor_prmtop PRMTOP { {--ligand_crd CRD | --ligand_mol2 MOL2} {--receptor_crd CRD | --receptor_pdb PDB} | {--complex_crd CRD | --complex_pdb PDB} } [-v | --verbose] [-i | --iterations ITERATIONS] [-o | --online] [-m | --mpi] [--restraints restraint-type] [--doctests] [--randomize_ligand]
EXAMPLES
# Specify AMBER prmtop/crd files for ligand and receptor.
%prog --ligand_prmtop ligand.prmtop --receptor_prmtop receptor.prmtop --ligand_crd ligand.crd --receptor_crd receptor.crd --iterations 1000
# Specify (potentially multi-conformer) mol2 file for ligand and (potentially multi-model) PDB file for receptor.
%prog --ligand_prmtop ligand.prmtop --receptor_prmtop receptor.prmtop --ligand_mol2 ligand.mol2 --receptor_pdb receptor.pdb --iterations 1000
# Specify (potentially multi-model) PDB file for complex, along with flat-bottom restraints (instead of harmonic).
%prog --ligand_prmtop ligand.prmtop --receptor_prmtop receptor.prmtop --complex_pdb complex.pdb --iterations 1000 --restraints flat-bottom
# Specify (potentially multi-model) PDB file for complex, along with flat-bottom restraints (instead of harmonic); randomize ligand positions/orientations at start.
%prog --ligand_prmtop ligand.prmtop --receptor_prmtop receptor.prmtop --complex_pdb complex.pdb --iterations 1000 --restraints flat-bottom --randomize_ligand
NOTES
In atom ordering, receptor comes before ligand atoms.
"""
# Parse command-line arguments.
from optparse import OptionParser
parser = OptionParser(usage=usage)
parser.add_option(
"--ligand_mol2",
dest="ligand_mol2_filename",
default=None,
help="ligand mol2 file (can contain multiple conformations)",
metavar="LIGAND_MOL2")
parser.add_option("--receptor_pdb",
dest="receptor_pdb_filename",
default=None,
help="receptor PDB file (can contain multiple MODELs)",
metavar="RECEPTOR_PDB")
parser.add_option("--complex_pdb",
dest="complex_pdb_filename",
default=None,
help="complex PDB file (can contain multiple MODELs)",
metavar="COMPLEX_PDB")
parser.add_option("-v",
"--verbose",
action="store_true",
dest="verbose",
default=False,
help="verbosity flag")
parser.add_option("-i",
"--iterations",
dest="niterations",
default=None,
help="number of iterations",
metavar="ITERATIONS")
parser.add_option("-o",
"--online",
dest="online_analysis",
default=False,
help="perform online analysis")
parser.add_option("-m",
"--mpi",
action="store_true",
dest="mpi",
default=False,
help="use mpi if possible")
parser.add_option(
"--restraints",
dest="restraint_type",
default=None,
help=
"specify ligand restraint type: 'harmonic' or 'flat-bottom' (default: 'harmonic')"
)
parser.add_option(
"--output",
dest="output_directory",
default=None,
help=
"specify output directory---must be unique for each calculation (default: current directory)"
)
parser.add_option("--doctests",
action="store_true",
dest="doctests",
default=False,
help="run doctests first (default: False)")
parser.add_option(
"--randomize_ligand",
action="store_true",
dest="randomize_ligand",
default=False,
help="randomize ligand positions and orientations (default: False)")
parser.add_option("--ignore_signal",
action="append",
dest="ignore_signals",
default=[],
help="signals to trap and ignore (default: None)")
parser.add_option("--platform",
dest="platform",
default="CPU",
help="The platform to use when running simulations")
parser.add_option(
"--gpus_per_node",
dest="gpus_per_node",
type='int',
default=None,
help=
"number of GPUs per node to use for complex simulations during MPI calculations"
)
# Parse command-line arguments.
(options, args) = parser.parse_args()
if options.doctests:
print "Running doctests for all modules..."
import doctest
# TODO: Test all modules
import yank, oldrepex, alchemy, analyze, utils
(failure_count, test_count) = doctest.testmod(verbose=options.verbose)
if failure_count == 0:
print "All doctests pass."
sys.exit(0)
else:
print "WARNING: There were %d doctest failures." % failure_count
sys.exit(1)
# Check arguments for validity.
if not (options.ligand_mol2_filename):
parser.error("Please supply a ligand in mol2 format")
if not (options.receptor_pdb_filename):
parser.error("Please supply the receptor in pdb format")
if not (options.complex_pdb_filename):
print("Will combine ligand and receptor")
# Initialize MPI if requested.
if options.mpi:
# Initialize MPI.
try:
from mpi4py import MPI # MPI wrapper
hostname = os.uname()[1]
options.mpi = MPI.COMM_WORLD
if not MPI.COMM_WORLD.rank == 0:
options.verbose = False
MPI.COMM_WORLD.barrier()
if MPI.COMM_WORLD.rank == 0:
print "Initialized MPI on %d processes." % (
MPI.COMM_WORLD.size)
except Exception as e:
print e
parser.error("Could not initialize MPI.")
# Select simulation parameters.
# TODO: Allow user selection or intelligent automated selection of simulation parameters.
# NOTE: Simulation paramters are hard-coded for now.
# NOTE: Simulation parameters will be different for explicit solvent.
import simtk.openmm.app as app
nonbondedMethod = app.NoCutoff
implicitSolvent = app.OBC2
constraints = app.HBonds
removeCMMotion = False
#make ligand, receptor, complex objects
ligand = Mol2SystemBuilder(options.ligand_mol2_filename, "ligand")
receptor = BiomoleculePDBSystemBuilder(options.receptor_pdb_filename,
"receptor")
complex = ComplexSystemBuilder(ligand, receptor, "complex")
# DEBUG: Write out ligand, receptor, and complex system objects.
debug = False
if debug:
def write_file(outfile, contents):
outfile = open(outfile, 'w')
outfile.write(contents)
outfile.close()
for name in ['receptor', 'ligand', 'complex']:
system = vars()[name].system
serialized_system = system.__getstate__()
filename = name + '.system.xml'
print "Writing serialized %s to %s..." % (name, filename)
write_file(filename, serialized_system)
# Initialize YANK object.
from yank import Yank
yank = Yank(receptor=receptor.system,
ligand=ligand.system,
complex=complex.system,
complex_positions=[complex.coordinates_as_quantity],
output_directory=options.output_directory,
verbose=options.verbose)
# Configure YANK object with command-line parameter overrides.
if options.niterations is not None:
yank.niterations = int(options.niterations)
if options.verbose:
yank.verbose = options.verbose
if options.online_analysis:
yank.online_analysis = options.online_analysis
if options.restraint_type is not None:
yank.restraint_type = options.restraint_type
if options.randomize_ligand:
yank.randomize_ligand = True
if options.platform:
yank.platform = openmm.Platform.getPlatformByName(options.platform)
# Hard-coded cpuid:gpuid for Exxact 4xGPU nodes
# TODO: Replace this with something automated
# cpuid_gpuid_mapping = { 0:0, 1:1, 2:2, 3:3 }
#ncpus_per_node = None
# Run calculation.brbz
if options.mpi:
# Run MPI version.
yank.run_mpi(options.mpi, options.gpus_per_node)
else:
# Run serial version.
yank.run()
# Run analysis.
results = yank.analyze()
# Print/write results.
print results