def make_task_factory(residue_selectors, confine_design=None):
"""
Makes a TaskFactory with operations that leave the mutable residues
designable, restricts the nearby residues to repacking, and prevents
repacking of other residues.
Also includes the ability to take in a target residue mutatations text
file in the form:
res_number allowed_AAs
for example:
138 KR
All designable residues not listed in the file are restricted to repacking
and the listed residues are limited in their design options to those AAs
listed.
"""
design_set = residue_selectors['mutable']
repack_set = residue_selectors['packable']
other_set = residue_selectors['other']
prevent = PreventRepackingRLT() # No repack, no design
repack = RestrictToRepackingRLT() # No design
tf = TaskFactory()
tf.push_back(OperateOnResidueSubset(prevent, other_set))
tf.push_back(OperateOnResidueSubset(repack, repack_set))
# Everything else left designable by default
# Restricting design further
if confine_design:
trms = readfile(confine_design)
# Converting lines to a dict
limited_set = \
{int(line.split()[0]):line.split()[1] for line in trms}
# Converting residues in the dict to a selector
res_concatenated = str(limited_set.keys()).strip('[]').replace(' ','')
small_des_set = ResidueIndexSelector(res_concatenated)
now_only_repack = NotResidueSelector(small_des_set)
# Making residue selection excluding residues in the file and
# restricting them to repacking
no_longer_designable = AndResidueSelector()
no_longer_designable.add_residue_selector(design_set)
no_longer_designable.add_residue_selector(now_only_repack)
tf.push_back(OperateOnResidueSubset(repack, no_longer_designable))
# Limiting design on residues in the file
for res, AAs in limited_set.items():
designable_res = ResidueIndexSelector(str(res))
restrict_AAs = RestrictAbsentCanonicalAASRLT()
restrict_AAs.aas_to_keep(AAs)
tf.push_back(OperateOnResidueSubset(restrict_AAs, designable_res))
return tf
def create_design_task_factory(designable_res_indexes: list, active_site_positions: list = list(), \
neighborhood: float = 0, cystine: bool = True, noncanonical_amino_acids: list = list()):
task_factory = TaskFactory()
if len(noncanonical_amino_acids) > 0:
ncaa_palette = CustomBaseTypePackerPalette()
for ncaa in noncanonical_amino_acids:
ncaa_palette.add_type(ncaa)
task_factory.set_packer_palette(ncaa_palette)
task_factory.push_back(IncludeCurrent())
# Mutatable
designable_selector = ResidueIndexSelector(','.join(
str(designable_res_index)
for designable_res_index in designable_res_indexes))
if not cystine:
restriction = RestrictAbsentCanonicalAASRLT()
restriction.aas_to_keep('AGILPVFWYDERHKSTMNQ') # AGILPVFWYDERHKSTCMNQ
task_factory.push_back(
OperateOnResidueSubset(restriction, designable_selector))
# Repack
repack = RestrictToRepackingRLT()
prevent = PreventRepackingRLT()
if neighborhood > 0:
if len(active_site_positions) > 0:
enzdes_cst_selector = ResidueIndexSelector(','.join(
str(enzdes_cst_index)
for enzdes_cst_index in active_site_positions))
designable_repacking_selector = NeighborhoodResidueSelector()
designable_repacking_selector.set_focus_selector(
OrResidueSelector(designable_selector, enzdes_cst_selector))
designable_repacking_selector.set_distance(neighborhood)
designable_repacking_selector.set_include_focus_in_subset(True)
repacking_selector = AndResidueSelector(
designable_repacking_selector,
NotResidueSelector(designable_selector))
task_factory.push_back(
OperateOnResidueSubset(repack, repacking_selector))
task_factory.push_back(
OperateOnResidueSubset(prevent, designable_repacking_selector,
True))
else:
repacking_selector = NeighborhoodResidueSelector()
repacking_selector.set_focus_selector(designable_selector)
repacking_selector.set_distance(neighborhood)
repacking_selector.set_include_focus_in_subset(False)
task_factory.push_back(
OperateOnResidueSubset(repack, repacking_selector))
task_factory.push_back(OperateOnResidueSubset(prevent, \
OrResidueSelector(designable_selector, repacking_selector), True))
else:
task_factory.push_back(
OperateOnResidueSubset(repack, designable_selector, True))
return task_factory
def task_factory_builder(repacking_residues='all', designing_residues=None, \
extra_rotamers=[1,2]):
#Setting this up for now, need to implement these conditions:
#Repackable set, Designable Set, prevent ligand repacking
#Building a Task Factory for repacking/design around the neighbors residues
#Task factory builder should accept: repackable residues, designable
#residues, specifically preventing repacking residues, and prevent the rest.
#tf = task_factory_builder(repack=repacking_neighbors)
#distance - distance for Neighborhood residue selector - need to remov
print_out("Building task factory")
#Start up Task factory, starting ex1 and ex2, and include current
tf = TaskFactory()
tf.push_back(IncludeCurrent())
if extra_rotamers:
for x in extra_rotamers:
tf.push_back(ExtraRotamers(0, x, 1))
print(repacking_residues)
#Set up repack and prevent repack
repack = RestrictToRepackingRLT()
prevent = PreventRepackingRLT()
prevent_everything_else = NotResidueSelector()
residues_for_repack = None
residues_for_design = None
changing_residues = OrResidueSelector()
if repacking_residues != 'all':
print_out("Repacking these residues: " + str(repacking_residues))
residues_for_repack = ResidueIndexSelector(
','.join(repacking_residues))
changing_residues.add_residue_selector(residues_for_repack)
tf.push_back(OperateOnResidueSubset(repack, residues_for_repack))
if designing_residues:
residues_for_design = ResidueIndexSelector(designing_residues)
changing_residues.add_residue_selector(residues_for_design)
prevent_everything_else.set_residue_selector(changing_residues)
if repack == 'all':
tf.push_back(OperateOnResidueSubset(repack, prevent_everything_else))
else:
tf.push_back(OperateOnResidueSubset(prevent, prevent_everything_else))
return tf
def make_task_factory(repackable_selection):
"""
Creates a task factory with residues in a selection repackable (not
designable), and all other residues fixed.
"""
# Repack options
prevent = PreventRepackingRLT() # No repack, no design
repack = RestrictToRepackingRLT() # No design
# Creating compliment selection
fixed_selection = NotResidueSelector(repackable_selection)
# Making task factory
tf = TaskFactory()
tf.push_back(OperateOnResidueSubset(prevent, fixed_selection))
tf.push_back(OperateOnResidueSubset(repack, repackable_selection))
return tf
def make_point_mutant_task_factory(site_1,
change_1,
site_2=None,
change_2=None,
fast=True):
"""
Given a site integer and a 1-letter residue name (or two sites and two
residue names), generates a TaskFactory to repack all residues
in a pose with the altered sites repacking to the new sequence.
"""
# Initialize selection of all altered residues
modified_residues = OrResidueSelector() # Keep list of mobile residues
# Make TaskFactory to input changes
task_factory = TaskFactory()
task_factory.push_back(IncludeCurrent())
if not fast:
task_factory.push_back(ExtraRotamers(0, 1, 1))
task_factory.push_back(ExtraRotamers(0, 2, 1))
# Force packing to new residue for the mutated site
res_selection_1 = ResidueIndexSelector(str(site_1))
aa_force_1 = RestrictAbsentCanonicalAASRLT()
aa_force_1.aas_to_keep(change_1)
task_factory.push_back(OperateOnResidueSubset(aa_force_1, res_selection_1))
modified_residues.add_residue_selector(res_selection_1)
# Add second site if necessary
if site_2 and change_2:
res_selection_2 = ResidueIndexSelector(str(site_2))
aa_force_2 = RestrictAbsentCanonicalAASRLT()
aa_force_2.aas_to_keep(change_2)
task_factory.push_back(
OperateOnResidueSubset(aa_force_2, res_selection_2))
modified_residues.add_residue_selector(res_selection_2)
# Repack all other residues to accommodate substitutions
unchanged_residues = NotResidueSelector(modified_residues)
repack = RestrictToRepackingRLT()
task_factory.push_back(OperateOnResidueSubset(repack, unchanged_residues))
return task_factory
def make_task_factory(residue_selectors):
"""
Makes a TaskFactory with operations that leave the mutable residues
designable, restricts the nearby residues to repacking, and prevents
repacking of other residues.
"""
mutable_set = residue_selectors['mutable']
repack_set = residue_selectors['packable']
immobile_set = residue_selectors['immobile']
prevent = PreventRepackingRLT() # No repack, no design
repack = RestrictToRepackingRLT() # No design
tf = TaskFactory()
tf.push_back(IncludeCurrent())
tf.push_back(ExtraRotamers(0, 1, 1))
tf.push_back(ExtraRotamers(0, 2, 1))
tf.push_back(OperateOnResidueSubset(prevent, immobile_set))
tf.push_back(OperateOnResidueSubset(repack, repack_set))
# Everything else left designable by default
return tf
def create_relax_task_factory(point_mutations: list = list(),
active_site_positions: list = list(),
neighborhood: float = 0):
task_factory = TaskFactory()
task_factory.push_back(IncludeCurrent())
repack = RestrictToRepackingRLT()
prevent = PreventRepackingRLT()
if len(point_mutations) > 0:
# Mutate
mutated_selector = OrResidueSelector()
for point_mutation in point_mutations:
mutation_info = point_mutation.split(',')
restriction = RestrictAbsentCanonicalAASRLT()
restriction.aas_to_keep(mutation_info[1])
point_mutation_selector = ResidueIndexSelector(mutation_info[0])
task_factory.push_back(
OperateOnResidueSubset(restriction, point_mutation_selector))
mutated_selector.add_residue_selector(point_mutation_selector)
# Repack and static
if neighborhood > 0:
if len(active_site_positions) > 0:
# Repack
enzyme_core_selector = ResidueIndexSelector(','.join(
str(active_site_position)
for active_site_position in active_site_positions))
designable_repacking_selector = NeighborhoodResidueSelector()
designable_repacking_selector.set_focus_selector(
OrResidueSelector(mutated_selector, enzyme_core_selector))
designable_repacking_selector.set_distance(neighborhood)
designable_repacking_selector.set_include_focus_in_subset(True)
repacking_selector = AndResidueSelector(
designable_repacking_selector,
NotResidueSelector(mutated_selector))
task_factory.push_back(
OperateOnResidueSubset(repack, repacking_selector))
# Static
task_factory.push_back(
OperateOnResidueSubset(prevent,
designable_repacking_selector,
True))
else:
# Repack
repacking_selector = NeighborhoodResidueSelector()
repacking_selector.set_focus_selector(mutated_selector)
repacking_selector.set_distance(args.neighborhood)
repacking_selector.set_include_focus_in_subset(False)
task_factory.push_back(
OperateOnResidueSubset(repack, repacking_selector))
# Static
mutated_and_repacking_selector = OrResidueSelector(
mutated_selector, repacking_selector)
task_factory.push_back(
OperateOnResidueSubset(prevent,
mutated_and_repacking_selector,
True))
else:
# Repack
task_factory.push_back(
OperateOnResidueSubset(repack, mutated_selector, True))
else:
if neighborhood > 0:
if len(active_site_positions) > 0:
# Repack
enzyme_core_selector = ResidueIndexSelector(','.join(
str(active_site_position)
for active_site_position in active_site_positions))
repacking_selector = NeighborhoodResidueSelector()
repacking_selector.set_focus_selector(enzyme_core_selector)
repacking_selector.set_distance(neighborhood)
repacking_selector.set_include_focus_in_subset(True)
task_factory.push_back(
OperateOnResidueSubset(repack, repacking_selector))
# Static
task_factory.push_back(
OperateOnResidueSubset(prevent, repacking_selector, True))
else:
# Static
task_factory.push_back(PreventRepacking())
else:
# Repack
task_factory.push_back(RestrictToRepacking())
return task_factory
def make_residue_changes(pose, sf, subst_seq, subst_start, cat_res,
manual_muts):
"""
Applies substrate sequence changes and manual mutations to a given pose.
This is done through repacking, so unlike SimpleThreadingMover, the side
chains don't begin clashing. This means that the residue selectors will be
more accurate, and that design can begin without an initial relax step.
pose is a Rosetta pose
sf is a Rosetta scorefunction
subst_seq is a string (doesn't need to be uppercase)
subst_start is an integer corresponding to the first of a contiguous block
of residues to re-sequence
manual_muts is a list of two-member lists, of the following form:
[site, single-letter residue name]
"""
# Create dict of {res: AA} for changes to make
res_changes = {}
# Add manual mutations list
if manual_muts:
print("\nApplying point substitutions:")
for m in manual_muts:
res_changes[int(m[0])] = m[1].upper()
print(m[0], m[1].upper())
# Add substrate threading to list of res changes
print("\nInserting substrate sequence:\n{}".format(subst_seq))
subst_range = range(subst_start, subst_start + len(subst_seq))
for n, i in enumerate(subst_range):
res_changes[i] = subst_seq[n].upper()
# Make TaskFactory to input changes
mobile_residues = OrResidueSelector() # Keep list of mobile residues
tf = TaskFactory()
# Force packing to target residue for each desired change
for r, aa in res_changes.items():
res_selection = ResidueIndexSelector(str(r))
restriction = RestrictAbsentCanonicalAASRLT()
restriction.aas_to_keep(aa.upper())
tf.push_back(OperateOnResidueSubset(restriction, res_selection))
mobile_residues.add_residue_selector(res_selection)
# Repack nearby residues to accommodate substitutions
shell = NeighborhoodResidueSelector()
shell.set_focus_selector(mobile_residues)
shell.set_include_focus_in_subset(False)
shell.set_distance(8)
# Exclude catalytic residues
if cat_res:
catalytic = ResidueIndexSelector(','.join([str(i) for i in cat_res]))
not_catalytic = NotResidueSelector(catalytic)
shell = selector_intersection(shell, not_catalytic)
restrict = RestrictToRepackingRLT()
tf.push_back(OperateOnResidueSubset(restrict, shell))
# Prevent repacking of all other residues
unchanging = NotResidueSelector(OrResidueSelector(mobile_residues, shell))
prevent = PreventRepackingRLT()
tf.push_back(OperateOnResidueSubset(prevent, unchanging))
# Apply changes with PackRotamersMover
pt = tf.create_task_and_apply_taskoperations(pose)
prm = PackRotamersMover(sf, pt)
mutated_pose = Pose(pose)
prm.apply(mutated_pose)
return mutated_pose
'N446E': 'pdz_relaxed_2.pdb_designed_9.pdb'
}
for des, muts in res_changes.items():
pp = pose_from_pdb('pdz_designs/examples/' + start_pdb[des])
peptide = ChainSelector('B')
shell = NeighborhoodResidueSelector()
shell.set_focus_selector(peptide)
shell.set_include_focus_in_subset(True)
shell.set_distance(12)
mobile_residues = OrResidueSelector()
tf = TaskFactory()
tf.push_back(IncludeCurrent())
tf.push_back(ExtraRotamers(0, 1, 1))
tf.push_back(ExtraRotamers(0, 2, 1))
for r, aa in muts.items():
res_selection = ResidueIndexSelector(str(r))
restriction = RestrictAbsentCanonicalAASRLT()
restriction.aas_to_keep(aa.upper())
tf.push_back(OperateOnResidueSubset(restriction, res_selection))
mobile_residues.add_residue_selector(res_selection)
packable = AndResidueSelector(shell, NotResidueSelector(mobile_residues))
tf.push_back(OperateOnResidueSubset(RestrictToRepackingRLT(), packable))
not_changing = NotResidueSelector(shell)
tf.push_back(OperateOnResidueSubset(PreventRepackingRLT(), not_changing))
pt = tf.create_task_and_apply_taskoperations(pose)
prm = PackRotamersMover(sf, pt)
prm.apply(pp)
pp.dump_pdb('pdz_designs/design_models/pdz_' + des + '.pdb')
# Run analyze_design_decoys.fix_file()
# python relax_new_pdb.py $i -od fibrils_collaboration/pdz_designs/design_models/round_2/ -cst fibrils_collaboration/htra1_pdz.cst -ccw 0 -n 10
peptide = ChainSelector('B')
designable = shell_selection(pdz, peptide, 6)
packable = shell_selection(pdz, designable, 6)
mobile = OrResidueSelector(designable, packable)
mobile.add_residue_selector(peptide)
static = NotResidueSelector(mobile)
sf = get_fa_scorefxn()
tf = TaskFactory()
tf.push_back(IncludeCurrent())
tf.push_back(ExtraRotamers(0, 1, 1))
tf.push_back(ExtraRotamers(0, 2, 1))
prevent = PreventRepackingRLT() # No repack, no design
repack = RestrictToRepackingRLT() # No design
tf.push_back(OperateOnResidueSubset(prevent, static))
tf.push_back(OperateOnResidueSubset(repack, packable))
tf.push_back(OperateOnResidueSubset(repack, peptide))
fr = FastRelax()
fr.set_scorefxn(sf)
fd = FastDesign()
fd.set_scorefxn(sf)
fd.set_task_factory(tf)
pose = pose_from_pdb(args.model)
pose.fold_tree(make_fold_tree())
pose = apply_constraints(pose)
pose = thread_to_htra1('QDYEPEA', pose)
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)