def setup_fastrelax(sf, pose):
"""
Creates FastRelax mover with appropriate score function, movemap, and
packer rules. All sidechains are mobile, only substrate backbone is mobile.
"""
relax = FastRelax()
relax.set_scorefxn(sf)
# MoveMap
mm = MoveMap()
mm.set_chi(True)
for i in range(1, pose.total_residue() + 1):
if pose.residue(i).chain() == 2:
mm.set_bb(i, True)
relax.set_movemap(mm)
# Packer tasks
tf = standard_task_factory()
tf.push_back(RestrictToRepacking())
tf.push_back(IncludeCurrent())
tf.push_back(ExtraRotamers(0, 1, 1))
tf.push_back(ExtraRotamers(0, 2, 1))
relax.set_task_factory(tf)
return relax
def fast_relax_mutant(pose, task_factory, move_map, score_function, decoys=1):
"""
Runs Fast Relax on the mutant pose instead of just repack an minimize.
Can modify to take varying amounts of decoys.
"""
fast_relax = FastRelax(1)
fast_relax.set_scorefxn(score_function)
fast_relax.set_task_factory(task_factory)
fast_relax.set_movemap(move_map)
score_function(pose)
packer = task_factory.create_task_and_apply_taskoperations(pose)
print_out("packer task")
print_out(packer)
#sys.exit()
traj_idx = 0
lowest_energy = 1000.0
print_out("emd182::Running Fast Relax")
while traj_idx < decoys:
print_out("Round Number: " + str(traj_idx))
pose_copy = pr.Pose()
pose_copy.assign(pose)
print_out("emd182:: pose total residues: " + str(pose.total_residue()))
fast_relax.apply(pose_copy)
decoy_energy = total_energy(pose_copy, score_function)
if traj_idx == '0':
mutated_pose = pose_copy
lowest_energy = decoy_energy
elif decoy_energy < lowest_energy:
mutated_pose = pose_copy
lowest_energy = decoy_energy
traj_idx += 1
return mutated_pose
def setup_fastrelax(sf):
"""
Creates FastRelax mover with appropriate score function, movemap, and
packer rules. List of neighbor residues was generated using a 8A
PyMOL selection expansion around the peptide chain.
"""
relax = FastRelax()
relax.set_scorefxn(sf)
# MoveMap
mm = MoveMap()
mm.set_bb_true_range(106, 112)
neighbors = [
1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 22, 37,
38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 53, 59, 62, 69, 70, 71, 72,
73, 74, 75, 76, 77, 78, 79, 83, 85, 98, 100, 101, 103, 104, 105, 106,
107, 108, 109, 110, 111, 112
] # Did 8A selection separately
for n in neighbors:
mm.set_chi(n, True)
relax.set_movemap(mm)
# Packer tasks
tf = standard_task_factory()
tf.push_back(RestrictToRepacking())
tf.push_back(IncludeCurrent())
tf.push_back(ExtraRotamers(0, 1, 1))
tf.push_back(ExtraRotamers(0, 2, 1))
relax.set_task_factory(tf)
return relax
def get_relaxer_mover(pose,
score_function=DEFAULT.score_function,
no_constraints=DEFAULT.no_constraints,
c_weight=DEFAULT.c_weight):
"""
TO DO
"""
if score_function == "auto":
try:
score_function = get_fa_scorefxn()
except:
import pyrosetta
init()
score_function = get_fa_scorefxn()
else:
from pyrosetta.rosetta.core.scoring import ScoreFunction
assert type(score_function) == ScoreFunction, \
"Score function for relaxer mover must be of type ScoreFunction."
if no_constraints == False:
coordinates_constraint = CoordinateConstraintGenerator()
constraints = AddConstraints()
constraints.add_generator(coordinates_constraint)
constraints.apply(pose)
activate_constraints(score_function, c_weight)
task_factory = standard_task_factory()
task_factory.push_back(ExtraRotamers(0, 2, 1))
task_factory.push_back(RestrictToRepacking())
task_factory.push_back(IncludeCurrent())
fast_relax = FastRelax()
fast_relax.set_scorefxn(score_function)
fast_relax.set_task_factory(task_factory)
return fast_relax
def fast_relax_mover(score_function,
task_factory=None,
movemap=None,
repeats=5):
"""
Creates a FastRelax mover with a given score function. If a task factory
and/or movemap are provided, they will also be incorporated into the mover.
By default, FastRelax goes through five ramping cycles, but this number can
be adjusted with the repeats option.
"""
from pyrosetta.rosetta.protocols.relax import FastRelax
# Make FastRelax mover with given score function
fr = FastRelax(repeats)
fr.set_scorefxn(score_function)
# Set task factory
if task_factory:
fr.set_task_factory(task_factory)
# Set move map
if movemap:
fr.set_movemap(movemap)
return fr
def setup_fastrelax(sf): """ Creates FastRelax mover with appropriate score function, movemap, and packer rules. List of neighbor residues was generated using a 10A neighborhood residue selector around the peptide chain. """ relax = FastRelax() relax.set_scorefxn(sf) # MoveMap mm = MoveMap() mm.set_bb_true_range(212,216) neighbors = [28, 29, 41, 42, 43, 44, 45, 46, 59, 60, 61, 62, 91, 125, 126, 127, 128, 129, 145, 147, 148, 149, 150, 151, 157, 164, 165, 166, 167, 168, 169, 170, 171, 183, 184, 185, 186, 187, 188, 189, 192, 193, 194, 212, 213, 214, 215, 216, 217, 218, 219, 220] # Did 10A selection separately for n in neighbors: mm.set_chi(n, True) relax.set_movemap(mm) # Packer tasks tf = standard_task_factory() tf.push_back(RestrictToRepacking()) tf.push_back(IncludeCurrent()) tf.push_back(ExtraRotamers(0, 1, 1)) tf.push_back(ExtraRotamers(0, 2, 1)) relax.set_task_factory(tf) return relax
def create_fast_relax_mover(score_function, task_factory, move_map=None):
# Make FastRelax mover
fast_relax = FastRelax()
fast_relax.set_scorefxn(score_function)
fast_relax.set_task_factory(task_factory)
if move_map:
fast_relax.set_movemap(move_map)
return fast_relax
def fastrelax(pose, score_function, movemap): """ Runs the FastRelax protocol on a pose, using given score function and movemap """ relax = FastRelax() relax.set_scorefxn(score_function) relax.set_movemap(movemap) relax.apply(pose) return pose
def main(args):
# Destination folder for PDB files
od = out_directory(args.out_dir)
# Determining file name
if args.name:
file_name = args.name
else:
file_name = basename(args.pdb_file).replace('.pdb',
'').replace('.gz', '')
file_name += '_relaxed'
out_name = join(od, file_name)
# Loading pose and applying constraints, symmetry,
pose = load_pose(args.pdb_file,
enzdes_cst=args.constraints,
coord_cst=True,
symmetry=args.symmetry,
membrane=None)
# Setting up the scorefunction with the desired constraint weights
sf = get_sf(rep_type='hard',
symmetry=args.symmetry,
membrane=0,
constrain=args.constraint_weight)
# Creating FastRelax protocol with the given score function
fr = FastRelax()
fr.set_scorefxn(sf)
# Packer tasks
tf = standard_task_factory()
tf.push_back(RestrictToRepacking())
tf.push_back(IncludeCurrent())
tf.push_back(ExtraRotamers(0, 1, 1))
tf.push_back(ExtraRotamers(0, 2, 1))
fr.set_task_factory(tf)
# RMSD metric
rmsdm = RMSDMetric()
rmsdm.set_comparison_pose(pose)
# Running relax set
jd = PyJobDistributor(out_name, args.n_decoys, sf)
while not jd.job_complete:
pp = Pose(pose)
fr.apply(pp)
rmsdm.apply(pp)
jd.output_decoy(pp)
print("Starting relax {}".format(pdb_name))
pose = fastrelax(pose, sf, mm, taskfactory=tf)
def fastrelax(pose, score_function, movemap, taskfactory=None):
"""
Runs the FastRelax protocol on a pose, using given score function and
movemap, and optionally a task factory. By default, FastRelax will not do
design. However, given a task factory that enables design, it functions
like FastDesign.
"""
relax = FastRelax()
relax.set_scorefxn(score_function)
relax.set_movemap(movemap)
if taskfactory:
relax.set_task_factory(taskfactory)
pp = Pose(pose)
relax.apply(pp)
return pp
def __init__(self, net, pose, fix=None, glycinate=False, max_iter=100,
n_moves=1, scorefxn=None, kT=0.1, k=15, dropout=0.5, relax=True):
super(NetPackMover, self).__init__(net, pose, k=k, dropout=dropout)
self.relax = relax
self.n_moves = n_moves
self.max_iter = max_iter
self.kT = kT
self.scorefxn = scorefxn
self.fix = fix if fix is not None else []
self.step = 0
self.fastrelax = ...
if relax or glycinate:
fastrelax = FastRelax()
fastrelax.set_scorefxn(self.scorefxn)
mm = MoveMap()
mm.set_bb(False)
mm.set_chi(True)
#for fixed in self.fix:
# mm.set_chi(fixed, False)
fastrelax.set_movemap(mm)
self.fastrelax = fastrelax
if glycinate:
self.dropout = 1.0
mask = torch.tensor([
1 - int(self.fixed_position(idx))
for idx in range(len(pose.sequence()))
], dtype=torch.bool)
for idx, residue in enumerate(pose.residues):
residue_name = self.sample_residue(pose, idx, mask=mask, argmax=True)
if not self.fixed_position(idx):
mutate_residue(pose, idx + 1, residue_name, pack_radius=10.0, pack_scorefxn=scorefxn)
mask[idx] = 0
self.dropout = dropout
self.fastrelax.apply(pose)
self.monte_carlo = MonteCarlo(pose, scorefxn, kT)
self.glycinate = glycinate
def relax(pdb, native, scorefxn=scorefxn_fa):
"""
Performs energy minimization using Rosetta FastRelax protocol, superimpose onto native structure, and calculate RMSD
--------
Params
- pdb (str): path to input structure in PDB format
- native (str): path to native structure in PDB format
- scorefxn (ScoreFunction): energy function to use in scoring. Either centroid ('score3') or full-atom ('fa_standard'), default full-atom
Returns
- Protein object representing relaxed structure
- RMSD between input and native (float)
- Score after minimization (float)
"""
pose = pose_from_pdb(pdb)
score = score_pose(pose, scorefxn)
print('initial score', score)
to_fullatom = SwitchResidueTypeSetMover('fa_standard')
to_fullatom.apply(pose)
relax = FastRelax() #ClassicRelax()
relax.set_scorefxn(scorefxn)
relax.apply(pose)
score = score_pose(pose, scorefxn)
print('final score', score)
pose.dump_pdb("%s_fast_relax.pdb" % (pdb[:-4]))
native_pose = pose_from_pdb(native)
relax.apply(native_pose)
native_pose.dump_pdb("%s_fast_relax.pdb" % (native[:-4]))
rmsd = superimpose_rmsd("%s_fast_relax.pdb" % (pdb[:-4]),
"%s.pdb" % (native[:-4]))
print('RMSD to native', rmsd)
return Protein(pose=pose), rmsd, score
def main(args):
init()
sf = create_score_function('ref2015_cst')
sf.set_weight(ScoreType(1).atom_pair_constraint,
2) # Increasing repulsion weight
sf.set_weight(ScoreType(1).dihedral_constraint,
0.5) # Reducing dihedral weight
def_score = get_fa_scorefxn()
if not isdir(args.outdir):
makedirs(args.outdir)
# Reading in PDB, determining middle chain
pose = pose_from_pdb(args.start_struct)
chain_count = pose.num_chains()
chain_no = chain_count / 2
# Determining which sites to tug
if args.test_single:
tug_sites = [args.test_single]
else:
chain_residues = selector_to_list(pose, get_mobile_range(chain_no))
tug_sites = chain_residues[1::args.frame] # First res will error
# Error because dihedrals are calculated using the upstream residue
# Making decoy set for each sliding frame on the tau middle monomer
for site in tug_sites:
in_res = int(pose.pdb_info().pose2pdb(site).split()[0])
site_name = join(args.outdir, 'tau_fibril_distort_' + str(in_res))
# Determining backbone-mobile section of pose
if args.mobile_range:
mobile_selection = get_mobile_range(chain_no, \
central_res=in_res, range_from_tug=args.mobile_range)
else:
mobile_selection = get_mobile_range(chain_no)
# Selecting repackable shell within 18A of the target (includes target)
ris = ResidueIndexSelector(str(site))
nrs = NeighborhoodResidueSelector(ris, 18)
# Combining selections
combined_selection = OrResidueSelector()
combined_selection.add_residue_selector(mobile_selection)
combined_selection.add_residue_selector(nrs)
# Making move map and task factory for FastRelax
mm = make_move_map(pose, mobile_selection, combined_selection)
tf = make_task_factory(combined_selection)
# Making FastRelax
fr = FastRelax()
fr.set_scorefxn(sf)
fr.set_movemap(mm)
fr.set_task_factory(tf)
# Making constraints
csts = make_constraints(pose, chain_no, site, args.tug_distance)
# Making ten decoys
jd = PyJobDistributor(site_name, args.num_decoys, sf)
while not jd.job_complete:
p = Pose()
p.assign(pose)
# Add constraints
for c in csts:
p.add_constraint(c)
fr.apply(p)
print("\n" * 5, jd.current_name)
print(sf.show(p), "\n" * 5)
jd.output_decoy(p)
#!/usr/bin/python
from glob import glob
from os.path import basename, join
from pyrosetta import *
from pyrosetta.rosetta.protocols.relax import FastRelax
init()
sf = create_score_function('ref2015_cst')
fr = FastRelax()
fr.set_scorefxn(sf)
fr.constrain_coords(True)
fr.constrain_relax_to_start_coords(True)
fr.coord_constrain_sidechains(True)
structs = glob('pdz_nmr/*.pdb')
structs.sort()
for s in structs:
pose = pose_from_pdb(s)
jdname = join('pdz_relax/', basename(s).rstrip('.pdb'))
jd = PyJobDistributor(jdname, 20, sf)
while not jd.job_complete:
pp = Pose()
pp.assign(pose)
fr.apply(pp)
jd.output_decoy(pp)
# Ex. task_factory.push_back(ExtraRotamers(0, 1, 1)) # ex1
task_factory.push_back(ExtraRotamers(0, 2, 1)) # ex2
# FastRelax, by default, blocks 'design' on the regular rotamers. However,
# when adding the ExtraRotamers, new 'designable' rotamers are included
# and considered during the sampling. Therefore, the TaskFactory must
# re-restrict the rotamers to repackaging.
task_factory.push_back(RestrictToRepacking())
# Altough the PyRosetta manual states that the current rotamer is included
# by default, this does not seem to be true and therefore needs to be
# activated.
task_factory.push_back(IncludeCurrent())
# Define the FastRelax object with the correct score function and extra
# rotamers enabled
fast_relax = FastRelax()
fast_relax.set_scorefxn(score_function)
fast_relax.set_task_factory(task_factory)
fast_relax.apply(pose)
pose.dump_pdb(args.output + ".pdb")
# A U X I L I A R Y F U N C T I O N S
# ______________________________________________________________________________
#
# Minimalistic version of the above script.
# Aimed to be called from other scripts.
def relax(pose,
no_constraints=DEFAULT.no_constraints,
c_weight=DEFAULT.c_weight):
def main(args):
# Destination folder for PDB files
if args.out_dir:
dir_name = args.out_dir
if not isdir(dir_name):
makedirs(dir_name)
else:
dir_name = ""
# Creating coordinate constraints for the entire molecule
cg = CoordinateConstraintGenerator()
ac = AddConstraints()
ac.add_generator(cg)
# Create enzdes constraints
if args.constraints:
enz_cst = AddOrRemoveMatchCsts()
enz_cst.set_cst_action(ADD_NEW)
# Creating symmetry setup
if args.symmetry:
sfsm = SetupForSymmetryMover(args.symmetry)
# Setting up the scorefunction with the desired constraint weights
if args.symmetry:
sf = SymmetricScoreFunction()
sf.add_weights_from_file(args.score_function)
else:
sf = create_score_function(args.score_function)
if args.coord_wt:
sf.set_weight(st.coordinate_constraint, args.coord_wt)
if args.enzdes_wt:
sf.set_weight(st.atom_pair_constraint, args.enzdes_wt)
sf.set_weight(st.angle_constraint, args.enzdes_wt)
sf.set_weight(st.dihedral_constraint, args.enzdes_wt)
# Creating FastRelax protocol with the given score function
fr = FastRelax()
fr.set_scorefxn(sf)
# Packer tasks
tf = standard_task_factory()
tf.push_back(RestrictToRepacking())
tf.push_back(IncludeCurrent())
tf.push_back(ExtraRotamers(0, 1, 1))
tf.push_back(ExtraRotamers(0, 2, 1))
fr.set_task_factory(tf)
# Determining file name
if args.name:
file_name = args.name
else:
file_name = basename(args.pdb_file).replace('.pdb', '').replace('.gz', '')
file_name += '_relaxed'
out_name = join(dir_name, file_name)
# Loading PDB file, applying constraints
pose = pose_from_pdb(args.pdb_file)
ac.apply(pose)
if args.constraints:
enz_cst.apply(pose)
if args.symmetry:
sfsm.apply(pose)
# RMSD metric
rmsdm = RMSDMetric()
rmsdm.set_comparison_pose(pose)
# Running relax set
jd = PyJobDistributor(out_name, args.n_decoys, sf)
while not jd.job_complete:
pp = Pose()
pp.assign(pose)
fr.apply(pp)
rmsdm.apply(pp)
jd.output_decoy(pp)
def main(args):
# Destination folder for PDB files
if args.out_dir:
dir_name = args.out_dir
if not isdir(dir_name):
makedirs(dir_name)
else:
dir_name = ""
# Creating coordinate constraints for the entire molecule
cg = CoordinateConstraintGenerator()
ac = AddConstraints()
ac.add_generator(cg)
# Create enzdes constraints
if args.constraints:
enz_cst = AddOrRemoveMatchCsts()
enz_cst.set_cst_action(ADD_NEW)
''' Declare the score function. '''
if args.symmetry: # Declare symmetric score functions
score_function = SymmetricScoreFunction()
if args.repulsive_type == 'hard':
if args.membrane:
score_function.add_weights_from_file('franklin2019')
else:
score_function.add_weights_from_file('ref2015')
elif args.repulsive_type == 'soft':
if args.membrane: # Set up a soft-rep version of franklin2019 manually
score_function.add_weights_from_file('ref2015_soft')
score_function.set_weight(ScoreType.fa_water_to_bilayer, 1.0)
else:
score_function.add_weights_from_file('ref2015_soft')
else: # Declare ordinary score functions
if args.repulsive_type == 'hard':
if args.membrane:
score_function = create_score_function('franklin2019')
else:
score_function = create_score_function('ref2015')
elif args.repulsive_type == 'soft':
if args.membrane: # Set up a soft-rep version of franklin2019 manually
score_function = create_score_function('ref2015_soft')
score_function.set_weight(ScoreType.fa_water_to_bilayer, 1.0)
else:
score_function = create_score_function('ref2015_soft')
if args.coord_wt:
score_function.set_weight(ScoreType.coordinate_constraint,
args.coord_wt)
if args.enzdes_wt:
score_function.set_weight(ScoreType.atom_pair_constraint,
args.enzdes_wt)
score_function.set_weight(ScoreType.angle_constraint, args.enzdes_wt)
score_function.set_weight(ScoreType.dihedral_constraint,
args.enzdes_wt)
# Loading PDB file
pose = pose_from_pdb(args.pdb_file)
if args.symmetry: # Applying symmetry if specified
sfsm = SetupForSymmetryMover(args.symmetry)
sfsm.apply(pose)
if args.membrane: # Set up membrane for membrane protein
add_memb = SymmetricAddMembraneMover(args.span_file)
add_memb.apply(pose)
else:
if args.membrane: # Set up membrane for membrane protein
add_memb = AddMembraneMover(args.span_file)
add_memb.apply(pose)
# Creating FastRelax protocol with the given score function
fr = FastRelax()
fr.set_scorefxn(score_function)
# Packer tasks
tf = standard_task_factory()
tf.push_back(IncludeCurrent())
tf.push_back(ExtraRotamers(0, 1, 1))
tf.push_back(ExtraRotamers(0, 2, 1))
protein_selector = ResiduePropertySelector(ResidueProperty.PROTEIN)
repack = RestrictToRepackingRLT()
tf.push_back(OperateOnResidueSubset(repack, protein_selector))
prevent = PreventRepackingRLT()
tf.push_back(OperateOnResidueSubset(prevent, protein_selector, True))
fr.set_task_factory(tf)
move_map = MoveMap()
if args.repulsive_type == 'hard':
move_map.set_bb(True)
elif args.repulsive_type == 'soft':
''' When using the soft-rep score function, backbone should be fixed. '''
move_map.set_bb(False)
protein_res_true_vector = protein_selector.apply(pose)
move_map.set_chi(protein_res_true_vector)
fr.set_movemap(move_map)
# Determining file name
if args.name:
file_name = args.name
else:
file_name = basename(args.pdb_file).replace('.pdb', '_relaxed')
out_name = join(dir_name, file_name)
# Applying constraints
ac.apply(pose)
if args.constraints:
enz_cst.apply(pose)
# RMSD metric
rmsdm = RMSDMetric()
rmsdm.set_comparison_pose(pose)
print(tf.create_task_and_apply_taskoperations(pose))
# Running relax set
jd = PyJobDistributor(out_name, args.n_decoys, score_function)
while not jd.job_complete:
pp = Pose()
pp.assign(pose)
fr.apply(pp)
rmsdm.apply(pp)
jd.output_decoy(pp)