def build_cgmodel(rosetta_scoring):
# Set values for the parameters in our coarse grained model:
polymer_length = 2
backbone_lengths = [1]
sidechain_lengths = [1]
sidechain_positions = [0]
include_bond_forces = False # NOTE: By default bonds are constrained to their equilibrium lengths, even when this variable is set to False, unless 'constrain_bonds'=False
constrain_bonds = True
include_bond_angle_forces = False
include_nonbonded_forces = True
include_torsion_forces = False
# Particle properties
mass = 100.0 * unit.amu
masses = {'backbone_bead_masses': mass, 'sidechain_bead_masses': mass}
bond_length = 1.0 * unit.angstrom
bond_lengths = {
'bb_bb_bond_length': bond_length,
'bb_sc_bond_length': bond_length,
'sc_sc_bond_length': bond_length
}
bond_force_constant = 0.0 * unit.kilocalorie_per_mole / unit.nanometer / unit.nanometer
bond_force_constants = {
'bb_bb_bond_k': bond_force_constant,
'bb_sc_bond_k': bond_force_constant,
'sc_sc_bond_k': bond_force_constant
}
r_min = bond_length
sigma = r_min / (2.0**(1 / 6))
sigmas = {'bb_sigma': sigma, 'sc_sigma': sigma}
epsilon = 0.2 * unit.kilocalorie_per_mole
epsilons = {'bb_eps': epsilon, 'sc_eps': epsilon}
exclusions = True
# Get positions from a local PDB file written by PyRosetta, and modified (by hand) to have a geometry where the nonbonded interactions are easy to evaluate
cgmodel = CGModel(polymer_length=polymer_length,
backbone_lengths=backbone_lengths,
sidechain_lengths=sidechain_lengths,
sidechain_positions=sidechain_positions,
masses=masses,
sigmas=sigmas,
epsilons=epsilons,
bond_lengths=bond_lengths,
include_nonbonded_forces=include_nonbonded_forces,
include_bond_forces=include_bond_forces,
include_bond_angle_forces=include_bond_angle_forces,
include_torsion_forces=include_torsion_forces,
rosetta_scoring=rosetta_scoring,
exclusions=exclusions,
constrain_bonds=constrain_bonds)
pyrosetta_sequence = ''.join([
str('X[' + str(monomer['monomer_name']) + ']')
for monomer in cgmodel.sequence
])
pose = pyrosetta.pose_from_sequence(pyrosetta_sequence)
pose.dump_pdb("test_pyrosetta.pdb")
cgmodel.positions = PDBFile("test_pyrosetta.pdb").getPositions()
cgmodel.topology = build_topology(cgmodel)
return (cgmodel, pose)
def build_cgmodel(rosetta_scoring):
# Set values for the parameters in our coarse grained model:
polymer_length = 2
backbone_lengths = [1]
sidechain_lengths = [1]
sidechain_positions = [0]
include_bond_forces = False # NOTE: By default bonds are constrained to their equilibrium lengths, even when this variable is set to False, unless 'constrain_bonds'=False
constrain_bonds = True
include_bond_angle_forces = True
include_nonbonded_forces = True
include_torsion_forces = True
# Particle properties
mass = 100.0 * unit.amu
masses = {'backbone_bead_masses': mass, 'sidechain_bead_masses': mass}
bond_length = 1.0 * unit.angstrom
bond_lengths = {
'bb_bb_bond_length': bond_length,
'bb_sc_bond_length': bond_length,
'sc_sc_bond_length': bond_length
}
bond_force_constant = 0.0 * unit.kilocalorie_per_mole / unit.nanometer / unit.nanometer
bond_force_constants = {
'bb_bb_bond_k': bond_force_constant,
'bb_sc_bond_k': bond_force_constant,
'sc_sc_bond_k': bond_force_constant
}
r_min = bond_length
sigma = r_min / (2.0**(1 / 6))
sigmas = {'bb_sigma': sigma, 'sc_sigma': sigma}
epsilon = 10.0 * unit.kilocalorie_per_mole
epsilons = {'bb_eps': epsilon, 'sc_eps': epsilon}
exclusions = True
# Bond angle properties
bond_angle_force_constant = 2 * unit.kilocalorie_per_mole / unit.radian / unit.radian
bond_angle_force_constants = {
'bb_bb_sc_angle_k': bond_angle_force_constant
}
equil_bond_angle = 90.0 * (3.141 / 180.0)
equil_bond_angles = {'bb_bb_sc_angle_0': equil_bond_angle}
# Torsion properties
torsion_force_constant = 3 * unit.kilocalorie_per_mole / unit.radian / unit.radian
torsion_force_constants = {'sc_bb_bb_sc_torsion_k': torsion_force_constant}
torsion_periodicity = 1
torsion_periodicities = {'sc_bb_bb_sc_period': torsion_periodicity}
equil_torsion_angle = 0.0 * (3.141 / 180.0)
equil_torsion_angles = {'sc_bb_bb_sc_torsion_0': equil_torsion_angle}
# Get positions from a local PDB file written by PyRosetta, and modified (by hand) to have a geometry where the nonbonded interactions are easy to evaluate
cgmodel = CGModel(polymer_length=polymer_length,
backbone_lengths=backbone_lengths,
sidechain_lengths=sidechain_lengths,
sidechain_positions=sidechain_positions,
masses=masses,
sigmas=sigmas,
epsilons=epsilons,
bond_lengths=bond_lengths,
include_nonbonded_forces=include_nonbonded_forces,
include_bond_forces=include_bond_forces,
include_bond_angle_forces=include_bond_angle_forces,
include_torsion_forces=include_torsion_forces,
rosetta_scoring=rosetta_scoring,
exclusions=exclusions,
constrain_bonds=constrain_bonds,
equil_torsion_angles=equil_torsion_angles,
torsion_force_constants=torsion_force_constants,
torsion_periodicities=torsion_periodicities,
equil_bond_angles=equil_bond_angles,
bond_angle_force_constants=bond_angle_force_constants)
pyrosetta_sequence = ''.join([
str('X[' + str(monomer['monomer_name']) + ']')
for monomer in cgmodel.sequence
])
res_file_list = list(
set([
str(str(monomer['monomer_name']) + ".params")
for monomer in cgmodel.sequence
]))
res_file_list = " ".join(res_file_list)
assign_mm_atom_properties_with_cgopenmm_cgmodel(cgmodel)
exit()
pose = pyrosetta.pose_from_sequence(pyrosetta_sequence)
for residue_index in range(pose.total_residue()):
print(pose.residue(residue_index))
exit()
pose.dump_pdb("test_pyrosetta.pdb")
cgmodel.positions = PDBFile("test_pyrosetta.pdb").getPositions()
cgmodel.topology = build_topology(cgmodel)
return (cgmodel, pose)
except:
os.remove(output_data)
else:
replica_energies, replica_positions, replica_states = read_replica_exchange_data(
system=cgmodel.system,
topology=cgmodel.topology,
temperature_list=temperature_list,
output_data=output_data,
print_frequency=print_frequency)
steps_per_stage = round(total_steps / exchange_attempts)
minimum_energy_structure = get_native_structure(
replica_positions, replica_energies, temperature_list)
cgmodel.positions = minimum_energy_structure
pitch, radius, monomers_per_turn, residual = get_helical_parameters(
cgmodel)
pitch_list.append(pitch)
radius_list.append(radius)
monomers_per_turn_list.append(monomers_per_turn)
residual_list.append(residual)
data = open("helical_data.dat", "a")
data.write(
str(round(sigma._value, 3)) + " " + str(round(epsilon._value, 3)) +
" " + str(round(float(pitch), 3)) + " " +
str(round(float(radius), 3)) + " " +
str(round(float(monomers_per_turn), 3)) + " " +
run_simulation(cgmodel,output_directory,total_simulation_time,simulation_time_step,1.0*unit.kelvin,20,output_pdb="output.pdb",output_data="output.dat")
model_angle_list = cgmodel.bond_angle_list
angle_list = []
for angle in model_angle_list:
if all([cgmodel.get_particle_type(i) == "backbone" for i in angle]):
angle_list.append(angle)
init_pose = False
attempts = 0
max_attempts = 100
while not os.path.exists("native_structure.pdb"):
try:
print("reading in a structure")
cgmodel.positions = PDBFile("init.pdb").getPositions()
print("minimize the structure")
cgmodel.positions,energy,simulation = minimize_structure(cgmodel.topology,cgmodel.system,cgmodel.positions,temperature=1.0*unit.kelvin,simulation_time_step=simulation_time_step,output_data="output.dat",output_pdb="output.pdb")
print("minimization succeeded.")
if not os.path.exists(output_data):
print("performing replica exchange simulations")
replica_energies,replica_positions,replica_states = run_replica_exchange(cgmodel.topology,cgmodel.system,cgmodel.positions,temperature_list=temperature_list,simulation_time_step=simulation_time_step,total_simulation_time=total_simulation_time,print_frequency=print_frequency,output_data=output_data)
make_replica_pdb_files(cgmodel.topology,replica_positions)
else:
print("reading replica exchange simulation data")
replica_energies,replica_positions,replica_states = read_replica_exchange_data(system=cgmodel.system,topology=cgmodel.topology,temperature_list=temperature_list,output_data=output_data,print_frequency=print_frequency)
native_structure = get_native_structure(replica_positions,replica_energies,temperature_list)
cgmodel.positions = get_native_structure(replica_positions,replica_energies,temperature_list)
str(top_directory) + "/torsions_" +
str(round(bb_bb_bb_bb_equil_torsion_angle, 2)) + "_" +
str(round(sc_bb_bb_sc_equil_torsion_angle, 2)) + ".pdb")
minimum_energy_structures = get_minimum_energy_pose(
cgmodel.topology,
replica_energies,
replica_positions,
file_name=output_file)
#if not os.path.exists(output_data):
p_list = []
r_list = []
mpt_list = []
for structure in minimum_energy_structures:
cgmodel.positions = structure
pitch, radius, monomers_per_turn = get_helical_parameters(cgmodel)
p_list.append(pitch)
r_list.append(radius)
mpt_list.append(monomers_per_turn)
pitch = mean(np.array([float(p) for p in p_list]))
radius = mean(np.array([float(r) for r in r_list]))
monomers_per_turn = mean(np.array([float(mpt) for mpt in mpt_list]))
data = open("helical_data.dat", "a")
data.write(
str(round(bb_bb_bb_bb_equil_torsion_angle, 2)) + "_" +
str(round(sc_bb_bb_sc_equil_torsion_angle, 2)) + " " +
str(round(float(pitch), 3)) + " " + str(round(float(radius), 3)) +
" " + str(round(float(monomers_per_turn), 3)) + "\n")
data.close()
if os.path.exists(nonnative_ensemble_directory):
nonnative_ensemble, nonnative_ensemble_energies = get_ensemble_data(
cgmodel, nonnative_ensemble_directory)
if len(nonnative_ensemble) != nonnative_ensemble_size:
print("ERROR: " + str(len(nonnative_ensemble_energies)) +
" nonnative poses were found in existing output folders, but " +
str(nonnative_ensemble_size) + " poses were requested.")
print(
"This probably means that the requested ensemble size changed since the script was last run."
)
exit()
else:
os.mkdir(nonnative_ensemble_directory)
for pose in nonnative_ensemble:
cgmodel.positions = pose
write_ensemble_pdb(cgmodel,
ensemble_directory=nonnative_ensemble_directory)
if os.path.exists(native_ensemble_directory):
native_ensemble, native_ensemble_energies = get_ensemble_data(
cgmodel, native_ensemble_directory)
if len(native_ensemble_energies) != native_ensemble_size:
print("ERROR: " + str(len(native_ensemble_energies)) +
" native poses were found in existing output folders, but " +
str(native_ensemble_size) + " poses were requested.")
print(
"This probably means that the requested ensemble size changed since the script was last run."
)
exit()
else:
def build_cgmodel():
# Set values for the parameters in our coarse grained model:
polymer_length = 3
backbone_lengths = [1]
sidechain_lengths = [1]
sidechain_positions = [0]
include_bond_forces = False # NOTE: Bonds are constrained to their equilibrium lengths, by default, even when this variable is set to False.
include_bond_angle_forces = False
include_nonbonded_forces = True
include_torsion_forces = False
rosetta_scoring = True
# Particle properties
mass = 100.0 * unit.amu
masses = {'backbone_bead_masses': mass, 'sidechain_bead_masses': mass}
bond_length = 1.0 * unit.angstrom
bond_lengths = {
'bb_bb_bond_length': bond_length,
'bb_sc_bond_length': bond_length,
'sc_sc_bond_length': bond_length
}
bond_force_constant = 0.0 * unit.kilocalorie_per_mole / unit.nanometer / unit.nanometer
bond_force_constants = {
'bb_bb_bond_k': bond_force_constant,
'bb_sc_bond_k': bond_force_constant,
'sc_sc_bond_k': bond_force_constant
}
r_min = bond_length
sigma = r_min / (2.0**(1 / 6))
sigmas = {'bb_bb_sigma': sigma, 'sc_sc_sigma': sigma}
epsilon = 0.2 * unit.kilocalorie_per_mole
epsilons = {'bb_bb_eps': epsilon, 'sc_sc_eps': epsilon}
# Bond angle properties
bond_angle_force_constant = 2 * unit.kilocalorie_per_mole / unit.radian / unit.radian
bond_angle_force_constants = {
'bb_bb_bb_angle_k': bond_angle_force_constant,
'bb_bb_sc_angle_k': bond_angle_force_constant
}
equil_bond_angle = 120.0 * (3.141 / 180.0)
equil_bond_angles = {
'bb_bb_bb_angle_0': equil_bond_angle,
'bb_bb_sc_angle_0': equil_bond_angle
}
# Torsion properties
torsion_force_constant = 3
torsion_force_constants = {
'bb_bb_bb_bb_torsion_k': torsion_force_constant,
'sc_bb_bb_sc_torsion_k': 0.0,
'bb_bb_bb_sc_torsion_k': 0.0,
'sc_bb_bb_bb_torsion_k': 0.0
}
torsion_periodicity = 3
torsion_periodicities = {
'bb_bb_bb_bb_period': torsion_periodicity,
'sc_bb_bb_sc_period': 0,
'bb_bb_bb_sc_period': 0,
'sc_bb_bb_bb_period': 0
}
equil_torsion_angle = 0.0 * (3.141 / 180.0)
equil_torsion_angles = {
'bb_bb_bb_bb_torsion_0': equil_torsion_angle,
'sc_bb_bb_sc_torsion_0': 0.0,
'bb_bb_bb_sc_torsion_0': 0.0,
'sc_bb_bb_bb_torsion_0': 0.0
}
# Build a coarse grained model
cgmodel = CGModel(polymer_length=polymer_length,
backbone_lengths=backbone_lengths,
sidechain_lengths=sidechain_lengths,
sidechain_positions=sidechain_positions,
masses=masses,
sigmas=sigmas,
epsilons=epsilons,
bond_lengths=bond_lengths,
bond_force_constants=bond_force_constants,
bond_angle_force_constants=bond_angle_force_constants,
torsion_force_constants=torsion_force_constants,
equil_bond_angles=equil_bond_angles,
equil_torsion_angles=equil_torsion_angles,
include_nonbonded_forces=include_nonbonded_forces,
include_bond_forces=include_bond_forces,
include_bond_angle_forces=include_bond_angle_forces,
include_torsion_forces=include_torsion_forces,
rosetta_scoring=rosetta_scoring,
torsion_periodicities=torsion_periodicities)
# Get positions by building a pose with PyRosetta
pyrosetta_sequence = ''.join([
str('X[' + str(monomer['monomer_name']) + ']')
for monomer in cgmodel.sequence
])
pose = pyrosetta.pose_from_sequence(pyrosetta_sequence)
pose.dump_pdb("init.pdb")
cgmodel.positions = PDBFile("init.pdb").getPositions()
cgmodel.topology = build_topology(cgmodel)
return (cgmodel)
configurations,energies = get_decorrelated_samples(replica_positions,replica_energies,temperature_list)
max_num_samples = 0
for traj in configurations:
if len(traj) > max_num_samples:
max_num_samples = len(traj)
pitch_kn = np.zeros((len(configurations),max_num_samples))
radius_kn = np.zeros((len(configurations),max_num_samples))
mpt_kn = np.zeros((len(configurations),max_num_samples))
residual_kn = np.zeros((len(configurations),max_num_samples))
for traj_index in range(len(configurations)):
for pose_index in range(len(configurations[traj_index])):
cgmodel.positions = configurations[traj_index][pose_index]
pitch,radius,mpt,residual = get_helical_parameters(cgmodel)
pitch_kn[traj_index][pose_index] = pitch
radius_kn[traj_index][pose_index] = radius
mpt_kn[traj_index][pose_index] = mpt
residual_kn[traj_index][pose_index] = residual
max_pitch,min_pitch=None,None
max_radius,min_radius=None,None
max_mpt,min_mpt=None,None
max_residual,min_residual=None,None
for index in range(len(pitch_kn)):
for pitch in pitch_kn[index]:
if max_pitch == None: max_pitch = pitch
if min_pitch == None: min_pitch = pitch
ensemble_list = []
rmsd_cutoff = 2.0
for replica_index in range(len(replica_positions)):
trajectory = md.load(str("replica_" + str(replica_index + 1) + ".pdb"))
rmsds = md.rmsd(trajectory, native_structure)
rmsd_to_helical[replica_index] = rmsds
for rmsd_index in range(len(rmsd_to_helical[replica_index])):
if rmsd_to_helical[replica_index][rmsd_index] < rmsd_cutoff:
rmsd_list.append(rmsd_to_helical[replica_index][rmsd_index])
ensemble_list.append(replica_positions[replica_index][rmsd_index])
random.shuffle(ensemble_list)
file_index = 1
for pose in ensemble_list:
if file_index <= 100:
file_name = str("pose_" + str(file_index) + ".pdb")
cgmodel.positions = pose
write_pdbfile_without_topology(cgmodel, file_name)
target_traj = md.load(file_name)
aligned_target_traj = target_traj.superpose(native_structure)
cgmodel.positions = unit.Quantity(aligned_target_traj.xyz[0],
cgmodel.positions.unit)
write_pdbfile_without_topology(cgmodel, file_name)
file_index = file_index + 1
else:
exit()