def selector_union(*selectors):
""" Returns the intersection of any set of selectors """
union_selection = OrResidueSelector()
for s in selectors:
union_selection.add_residue_selector(s)
return union_selection
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 packable_residues_selector(mutable_selector):
"""
Selects the shell of neighbor residues to repack
Presently hard coded for HCV protease.
"""
# Selecting regions
mutable = mutable_selector
not_mutable = NotResidueSelector(mutable_selector)
catalytic = ResidueIndexSelector('72,96,154')
peptide = ChainSelector('B')
pep_not_mutable = AndResidueSelector()
pep_not_mutable.add_residue_selector(peptide)
pep_not_mutable.add_residue_selector(not_mutable)
# Selecting residues near mutable shell
near_mutable = InterGroupInterfaceByVectorSelector()
near_mutable.group1_selector(not_mutable)
near_mutable.group2_selector(mutable)
near_mutable.nearby_atom_cut(4)
near_mutable.vector_dist_cut(4)
# Selecting residues near the peptide
near_pep = InterGroupInterfaceByVectorSelector()
near_pep.group1_selector(not_mutable) # Protease
near_pep.group2_selector(peptide) # Peptide recognition region
near_pep.nearby_atom_cut(10)
near_pep.vector_dist_cut(12)
# Combining selections for near peptide and near mutable residues
wide_set = OrResidueSelector()
wide_set.add_residue_selector(near_mutable)
wide_set.add_residue_selector(near_pep)
# Setting up exclusion of catalytic and mutable residues
limit_selection = AndResidueSelector()
limit_selection.add_residue_selector(NotResidueSelector(catalytic))
limit_selection.add_residue_selector(wide_set)
limit_selection.add_residue_selector(not_mutable)
# Add back in the peptide
expand_selection = OrResidueSelector()
expand_selection.add_residue_selector(limit_selection)
expand_selection.add_residue_selector(pep_not_mutable)
return expand_selection
def ligand_neighbor_selection(lig, radius, pose, include_ligand=False):
rad = float(radius)
not_ligand = NotResidueSelector()
not_ligand.set_residue_selector(lig)
lig_distant_neighbors = InterGroupInterfaceByVectorSelector()
lig_distant_neighbors.group1_selector(lig)
lig_distant_neighbors.group2_selector(not_ligand)
lig_distant_neighbors.cb_dist_cut(2.0 * rad)
lig_distant_neighbors.nearby_atom_cut(rad)
lig_contacts = pr.rosetta.core.select.residue_selector.CloseContactResidueSelector(
)
lig_contacts.central_residue_group_selector(lig)
lig_contacts.threshold(rad)
lig_neighbors = OrResidueSelector()
lig_neighbors.add_residue_selector(lig_distant_neighbors)
lig_neighbors.add_residue_selector(lig_contacts)
if include_ligand:
selection = AndResidueSelector()
selection.add_residue_selector(not_ligand)
else:
selection = OrResidueSelector()
selection.add_residue_selector(lig)
selection.add_residue_selector(lig_neighbors)
return get_residues_from_subset(selection.apply(pose))
def other_residues_selector(mutable_selector, packable_selector): """ Selects the residues that are not designable or repackable """ all_mobile_res = OrResidueSelector() all_mobile_res.add_residue_selector(mutable_selector) all_mobile_res.add_residue_selector(packable_selector) other_res_selector = NotResidueSelector(all_mobile_res) return other_res_selector
def movemap_packable_residues_selector(peptides, mutables, packables): """ Combines selectors for all residues for which a MoveMap should set chi true. """ combined = OrResidueSelector() combined.add_residue_selector(peptides) combined.add_residue_selector(mutables) combined.add_residue_selector(packables) return combined
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_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 apply_constraints(pose):
"""
Applies enzdes constraints form the input CST file to a pose
Also applies coordinate constraints to the substrate peptide, assumed to
be chain B
"""
# Enzdes constraints
cstm = AddOrRemoveMatchCsts()
cstm.set_cst_action(ADD_NEW)
cstm.apply(pose)
# Coordinate constraints
cg = CoordinateConstraintGenerator()
ors = OrResidueSelector()
ors.add_residue_selector(ChainSelector('A')) # Constrain main backbone
ors.add_residue_selector(
ResidueIndexSelector('113-115')) # Preserving original peptide
cg.set_residue_selector(ors)
ac = AddConstraints()
ac.add_generator(cg)
ac.apply(pose)
return
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
def residue_selection(selection_one, selection_two):
#For now, just an or selector to group up the residues.
first = ResidueIndexSelector(selection_one)
second = ResidueIndexSelector(selection_one)
both = OrResidueSelector(first, second)
return both
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)
def main(args):
if args.ligand_type == 'ligand':
init_args = ' '.join(['-extra_res_fa', args.ligand_name])
lig_name = args.ligand_name.split('/')[-1].strip('.params')
else:
init_args = ''
pr.init(init_args)
sf = pr.get_fa_scorefxn()
sf.add_weights_from_file('ref2015')
pose = pr.pose_from_pdb(args.input_pdb)
sf(pose)
print_notice("Scaffold protein Loaded Successfully!")
print_notice("Scaffold protein has" + str(pose.total_residue()) +
"residues.")
if args.symmetric_file:
sfsm = SetupForSymmetryMover(args.symmetric_file)
sfsm.apply(pose)
#Importing list of residues if the ligand is a protein
if args.ligand_type == 'protein':
ligres = ResidueIndexSelector(args.residue_set)
#Targeting the ligand if the ligand isn't protein
elif args.ligand_type == 'ligand':
ligres = ResidueNameSelector()
ligres.set_residue_name3(lig_name)
print_notice("Ligand found at resnum: " + \
str(get_residues_from_subset(ligres.apply(pose))) )
#Setting the proteins not in the ligand
not_ligand = NotResidueSelector()
not_ligand.set_residue_selector(ligres)
#Setting the protein considered part of the ligand
ligand_distant_contacts = InterGroupInterfaceByVectorSelector()
ligand_distant_contacts.group1_selector(ligres)
ligand_distant_contacts.group2_selector(not_ligand)
ligand_distant_contacts.cb_dist_cut(2.5 * float(args.radius))
ligand_distant_contacts.nearby_atom_cut(float(args.radius))
#Test set: ClosecontactResidueSelector
close_contacts = pr.rosetta.core.select.residue_selector.CloseContactResidueSelector(
)
close_contacts.central_residue_group_selector(ligres)
close_contacts.threshold(float(args.radius))
all_contacts = OrResidueSelector()
all_contacts.add_residue_selector(close_contacts)
all_contacts.add_residue_selector(ligand_distant_contacts)
non_lig_residues = AndResidueSelector()
non_lig_residues.add_residue_selector(all_contacts)
non_lig_residues.add_residue_selector(not_ligand)
#Collecting the residues from the subset
neighbor_residues = get_residues_from_subset(non_lig_residues.apply(pose))
pdb_residues = []
for residue in neighbor_residues:
print(pose.pdb_info().pose2pdb(residue))
resid = pose.pdb_info().pose2pdb(residue).split()
pdb_residues.append(''.join(resid))
print_notice("Ligand found, neighbor residues are: " +
', '.join([x for x in pdb_residues]))
print_notice("Ligand found, total neighbor residues is " +
str(len(pdb_residues)))
#Removing residues in the REMARKS section
remove_set = []
f = open(args.input_pdb, 'r')
for line in f.readlines():
if 'REMARK' in line:
items = [x for x in line.split(' ') if x != '']
residue_set = [int(items[6]), int(items[11])]
for resi in residue_set:
if resi not in remove_set:
remove_set.append(resi)
residue_final_set = []
for resi in pdb_residues:
idx = int(resi[0:-1])
if idx not in remove_set:
residue_final_set.append(resi)
#Final list for the designable residues
residue_final_set.append('0')
print_notice("Neighbor residues cleaned \n \n Residues are: " +\
', '.join([x for x in residue_final_set]))
if args.out_file:
out_name = args.out_file
else:
out_name = args.input_pdb.strip('.pdb') + '_lig.pos'
f = open(out_name, "w")
for x in residue_final_set:
f.write(x + '\n')
f.close
print("emd182::Wrote ligand position residues of pdb file " +
args.input_pdb + " to filename: " + out_name)
'R386V-M388R-K394V': 'pdz_relaxed_2.pdb_designed_13.pdb',
'I415K': 'pdz_relaxed_2.pdb_designed_13.pdb',
'I415K-E416Y': 'pdz_relaxed_2.pdb_designed_13.pdb',
'R386V-M388R-K394V-T415K-E416Y': 'pdz_relaxed_2.pdb_designed_13.pdb',
'Y382W-R386V-M388R-K394V-T415K-E416Y': 'pdz_relaxed_2.pdb_designed_13.pdb',
'S389D-S444R-N446Q': 'pdz_relaxed_3.pdb_designed_47.pdb',
'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)
parser = argparse.ArgumentParser()
parser.add_argument('model', help='Select starting model.')
parser.add_argument('job', help='job from SLURM')
args = parser.parse_args()
#opts = '-use_input_sc -ex1 -ex2 -enzdes::cstfile htra1_pdz.cst -run:preserve_header'
opts = '-enzdes::cstfile htra1_pdz.cst -run:preserve_header'
init(opts)
pdz = ChainSelector('A')
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))