def filter_before_build (
pdb_hierarchy,
fmodel,
geometry_restraints_manager,
selection=None,
params=None,
verbose=True,
log=sys.stdout) :
"""
Pick residues suitable for building alternate conformations - by default,
this means no MolProbity/geometry outliers, good fit to map, no missing
atoms, and no pre-existing alternates, but with significant difference
density nearby.
"""
from mmtbx.validation import molprobity
from mmtbx.rotamer import rotamer_eval
import mmtbx.monomer_library.server
from mmtbx import building
from iotbx.pdb import common_residue_names_get_class
from scitbx.array_family import flex
if (selection is None) :
selection = flex.bool(fmodel.xray_structure.scatterers().size(), True)
pdb_atoms = pdb_hierarchy.atoms()
assert (pdb_atoms.size() == fmodel.xray_structure.scatterers().size())
pdb_atoms.reset_i_seq()
full_validation = molprobity.molprobity(
pdb_hierarchy=pdb_hierarchy,
fmodel=fmodel,
geometry_restraints_manager=geometry_restraints_manager,
outliers_only=False,
rotamer_library="8000")
if (verbose) :
full_validation.show(out=log)
multi_criterion = full_validation.as_multi_criterion_view()
if (params is None) :
params = libtbx.phil.parse(filter_params_str).extract()
mon_lib_srv = mmtbx.monomer_library.server.server()
two_fofc_map, fofc_map = building.get_difference_maps(fmodel=fmodel)
residues = []
filters = params.discard_outliers
make_sub_header("Identifying candidates for building", out=log)
# TODO parallelize
for chain in pdb_hierarchy.only_model().chains() :
if (not chain.is_protein()) :
continue
for residue_group in chain.residue_groups() :
atom_groups = residue_group.atom_groups()
id_str = residue_group.id_str()
i_seqs = residue_group.atoms().extract_i_seq()
residue_sel = selection.select(i_seqs)
if (not residue_sel.all_eq(True)) :
continue
if (len(atom_groups) > 1) :
print >> log, " %s is already multi-conformer" % id_str
continue
atom_group = atom_groups[0]
res_class = common_residue_names_get_class(atom_group.resname)
if (res_class != "common_amino_acid") :
print >> log, " %s: non-standard residue" % id_str
continue
missing_atoms = rotamer_eval.eval_residue_completeness(
residue=atom_group,
mon_lib_srv=mon_lib_srv,
ignore_hydrogens=True)
if (len(missing_atoms) > 0) :
# residues modeled as pseudo-ALA are allowed by default; partially
# missing sidechains are more problematic
if ((building.is_stub_residue(atom_group)) and
(not params.ignore_stub_residues)) :
pass
else :
print >> log, " %s: missing or incomplete sidechain" % \
(id_str, len(missing_atoms))
continue
validation = multi_criterion.get_residue_group_data(residue_group)
is_outlier = is_validation_outlier(validation, params)
if (is_outlier) :
print >> log, " %s" % str(validation)
continue
if (params.use_difference_map) :
i_seqs_no_hd = building.get_non_hydrogen_atom_indices(residue_group)
map_stats = building.local_density_quality(
fofc_map=fofc_map,
two_fofc_map=two_fofc_map,
atom_selection=i_seqs_no_hd,
xray_structure=fmodel.xray_structure,
radius=params.sampling_radius)
if ((map_stats.number_of_atoms_below_fofc_map_level() == 0) and
(map_stats.fraction_of_nearby_grid_points_above_cutoff()==0)) :
if (verbose) :
print >> log, " no difference density for %s" % id_str
continue
residues.append(residue_group.only_atom_group())
if (len(residues) == 0) :
raise Sorry("No residues passed the filtering criteria.")
print >> log, ""
print >> log, "Alternate conformations will be tried for %d residue(s):" % \
len(residues)
building.show_chain_resseq_ranges(residues, out=log, prefix=" ")
print >> log, ""
return residues
def __call__(self,
atom_group,
log,
window_size=2,
backbone_sample_angle=10,
anneal=False,
annealing_temperature=1000,
use_chi1_sampling=False):
import iotbx.pdb.hierarchy
from scitbx.array_family import flex
assert (atom_group is not None)
pdb_hierarchy = self.pdb_hierarchy.deep_copy()
xray_structure = self.xray_structure.deep_copy_scatterers()
geometry_restraints_manager = self.geometry_restraints_manager
# FIXME this doesn't work - can't recover the atom_group afterwards!
#hd_sel = xray_structure.hd_selection()
#n_hydrogen = hd_sel.count(True)
#if (n_hydrogen > 0):
# non_hd_sel = ~hd_sel
# pdb_hierarchy = pdb_hierarchy.select(non_hd_sel)
# xray_structure = xray_structure.select(non_hd_sel)
# geometry_restraints_manager = geometry_restraints_manager.select(
# non_hd_sel)
pdb_atoms = pdb_hierarchy.atoms()
pdb_atoms.reset_i_seq()
isel = building.extract_iselection([atom_group])
atom_group = pdb_atoms[isel[0]].parent()
atom_group_start = atom_group.detached_copy()
needs_rebuild = not building.is_stub_residue(atom_group)
residue_group = atom_group.parent()
assert (len(residue_group.atom_groups()) == 1)
sel_residues = building.get_window_around_residue(
residue=atom_group, window_size=window_size)
# get rid of sidechains for surrounding residues only
adjacent_residues = []
for other_rg in sel_residues:
if (other_rg != residue_group):
adjacent_residues.append(other_rg)
building.remove_sidechain_atoms(adjacent_residues)
pdb_atoms = pdb_hierarchy.atoms()
adjacent_trimmed_atom_names = pdb_atoms.extract_name()
adjacent_trimmed_sel = pdb_atoms.extract_i_seq()
xrs_adjacent_trimmed = xray_structure.select(adjacent_trimmed_sel)
grm_adjacent_trimmed = geometry_restraints_manager.select(
adjacent_trimmed_sel)
pdb_atoms.reset_i_seq()
# get rid of central sidechain and refine mainchain for entire window
truncate = (not atom_group.resname in ["GLY", "ALA"]) # XXX PRO?
if (truncate):
building.remove_sidechain_atoms([atom_group])
pdb_atoms = pdb_hierarchy.atoms()
all_mc_sel = pdb_atoms.extract_i_seq()
xrs_mc = xrs_adjacent_trimmed.select(all_mc_sel)
pdb_atoms.reset_i_seq()
window_mc_sel = building.extract_iselection(sel_residues)
selection = flex.bool(pdb_atoms.size(),
False).set_selected(window_mc_sel, True)
restraints_manager = grm_adjacent_trimmed.select(all_mc_sel)
box = building.box_build_refine_base(
xray_structure=xrs_mc,
pdb_hierarchy=pdb_hierarchy,
selection=selection,
processed_pdb_file=None,
target_map=self.target_map,
geometry_restraints_manager=restraints_manager.geometry,
d_min=self.d_min,
out=null_out(),
debug=True)
box.restrain_atoms(selection=box.others_in_box, reference_sigma=0.1)
box.real_space_refine(selection=box.selection_in_box)
sites_new = box.update_original_coordinates()
pdb_atoms.set_xyz(sites_new)
# extend and replace existing residue. this is done in such a way that
# the original atom ordering for the central residue is preserved, which
# allows us to use the pre-existing geometry restraints instead of
# re-calculating them every time this function is called.
target_atom_group = self.ideal_dict[atom_group.resname.lower()].\
only_model().only_chain().only_residue_group().only_atom_group()
new_atom_group_base = extend_sidechains.extend_residue(
residue=atom_group,
target_atom_group=target_atom_group,
mon_lib_srv=self.mon_lib_srv)
new_atom_group = iotbx.pdb.hierarchy.atom_group(
resname=atom_group.resname)
for atom in atom_group_start.atoms():
for new_atom in new_atom_group_base.atoms():
if (new_atom.name == atom.name):
new_atom_group.append_atom(new_atom.detached_copy())
n_atoms_new = len(new_atom_group.atoms())
n_atoms_start = len(atom_group_start.atoms())
if (n_atoms_new != n_atoms_start):
raise RuntimeError(
("Inconsistent atom counts for residue %s after " +
"building (%d versus %d).") %
(atom_group.id_str(), n_atoms_start, n_atoms_new))
rg = atom_group.parent()
rg.remove_atom_group(atom_group)
rg.append_atom_group(new_atom_group)
pdb_atoms = pdb_hierarchy.atoms()
pdb_atoms.reset_i_seq()
new_names = pdb_atoms.extract_name()
assert new_names.all_eq(adjacent_trimmed_atom_names)
# get new box around this residue
residue_sel = building.extract_iselection([new_atom_group])
selection = flex.bool(pdb_atoms.size(),
False).set_selected(residue_sel, True)
xrs_adjacent_trimmed.set_sites_cart(pdb_atoms.extract_xyz())
box = building.box_build_refine_base(
xray_structure=xrs_adjacent_trimmed,
pdb_hierarchy=pdb_hierarchy,
selection=selection,
processed_pdb_file=None,
target_map=self.target_map,
geometry_restraints_manager=grm_adjacent_trimmed.geometry,
d_min=self.d_min,
out=null_out(),
debug=True)
# place sidechain using mmtbx.refinement.real_space.fit_residue
if ((atom_group.resname in rotatable_sidechain_atoms)
and (use_chi1_sampling)):
fit_chi1_simple(residue=box.only_residue(),
unit_cell=box.unit_cell_box,
target_map=box.target_map_box,
rotamer_eval=self.rotamer_eval)
box.update_sites_from_pdb_atoms()
else:
box.fit_residue_in_box(backbone_sample_angle=backbone_sample_angle)
if (anneal):
box.anneal(start_temperature=annealing_temperature)
#box.real_space_refine()
sites_new = box.update_original_coordinates()
pdb_hierarchy.atoms().set_xyz(sites_new)
return building.atom_group_as_hierarchy(new_atom_group)
def __call__ (self,
atom_group,
log,
window_size=2,
backbone_sample_angle=10,
anneal=False,
annealing_temperature=1000,
use_chi1_sampling=False) :
import iotbx.pdb.hierarchy
from scitbx.array_family import flex
assert (atom_group is not None)
pdb_hierarchy = self.pdb_hierarchy.deep_copy()
xray_structure = self.xray_structure.deep_copy_scatterers()
geometry_restraints_manager = self.geometry_restraints_manager
# FIXME this doesn't work - can't recover the atom_group afterwards!
#hd_sel = xray_structure.hd_selection()
#n_hydrogen = hd_sel.count(True)
#if (n_hydrogen > 0) :
# non_hd_sel = ~hd_sel
# pdb_hierarchy = pdb_hierarchy.select(non_hd_sel)
# xray_structure = xray_structure.select(non_hd_sel)
# geometry_restraints_manager = geometry_restraints_manager.select(
# non_hd_sel)
pdb_atoms = pdb_hierarchy.atoms()
pdb_atoms.reset_i_seq()
isel = building.extract_iselection([atom_group])
atom_group = pdb_atoms[isel[0]].parent()
atom_group_start = atom_group.detached_copy()
needs_rebuild = not building.is_stub_residue(atom_group)
residue_group = atom_group.parent()
assert (len(residue_group.atom_groups()) == 1)
sel_residues = building.get_window_around_residue(
residue=atom_group,
window_size=window_size)
# get rid of sidechains for surrounding residues only
adjacent_residues = []
for other_rg in sel_residues :
if (other_rg != residue_group) :
adjacent_residues.append(other_rg)
building.remove_sidechain_atoms(adjacent_residues)
pdb_atoms = pdb_hierarchy.atoms()
adjacent_trimmed_atom_names = pdb_atoms.extract_name()
adjacent_trimmed_sel = pdb_atoms.extract_i_seq()
xrs_adjacent_trimmed = xray_structure.select(adjacent_trimmed_sel)
grm_adjacent_trimmed = geometry_restraints_manager.select(
adjacent_trimmed_sel)
pdb_atoms.reset_i_seq()
# get rid of central sidechain and refine mainchain for entire window
truncate = (not atom_group.resname in ["GLY","ALA"]) # XXX PRO?
if (truncate) :
building.remove_sidechain_atoms([ atom_group ])
pdb_atoms = pdb_hierarchy.atoms()
all_mc_sel = pdb_atoms.extract_i_seq()
xrs_mc = xrs_adjacent_trimmed.select(all_mc_sel)
pdb_atoms.reset_i_seq()
window_mc_sel = building.extract_iselection(sel_residues)
selection = flex.bool(pdb_atoms.size(), False).set_selected(window_mc_sel,
True)
restraints_manager = grm_adjacent_trimmed.select(all_mc_sel)
box = building.box_build_refine_base(
xray_structure=xrs_mc,
pdb_hierarchy=pdb_hierarchy,
selection=selection,
processed_pdb_file=None,
target_map=self.target_map,
geometry_restraints_manager=restraints_manager.geometry,
d_min=self.d_min,
out=null_out(),
debug=True)
box.restrain_atoms(
selection=box.others_in_box,
reference_sigma=0.1)
box.real_space_refine(selection=box.selection_in_box)
sites_new = box.update_original_coordinates()
pdb_atoms.set_xyz(sites_new)
# extend and replace existing residue. this is done in such a way that
# the original atom ordering for the central residue is preserved, which
# allows us to use the pre-existing geometry restraints instead of
# re-calculating them every time this function is called.
new_atom_group_base = extend_sidechains.extend_residue(
residue=atom_group,
ideal_dict=self.ideal_dict,
hydrogens=False,
mon_lib_srv=self.mon_lib_srv,
match_conformation=True)
new_atom_group = iotbx.pdb.hierarchy.atom_group(resname=atom_group.resname)
for atom in atom_group_start.atoms() :
for new_atom in new_atom_group_base.atoms() :
if (new_atom.name == atom.name) :
new_atom_group.append_atom(new_atom.detached_copy())
n_atoms_new = len(new_atom_group.atoms())
n_atoms_start = len(atom_group_start.atoms())
if (n_atoms_new != n_atoms_start) :
raise RuntimeError(("Inconsistent atom counts for residue %s after "+
"building (%d versus %d).") % (atom_group.id_str(), n_atoms_start,
n_atoms_new))
rg = atom_group.parent()
rg.remove_atom_group(atom_group)
rg.append_atom_group(new_atom_group)
pdb_atoms = pdb_hierarchy.atoms()
pdb_atoms.reset_i_seq()
new_names = pdb_atoms.extract_name()
assert new_names.all_eq(adjacent_trimmed_atom_names)
# get new box around this residue
residue_sel = building.extract_iselection([ new_atom_group ])
selection = flex.bool(pdb_atoms.size(), False).set_selected(residue_sel,
True)
xrs_adjacent_trimmed.set_sites_cart(pdb_atoms.extract_xyz())
box = building.box_build_refine_base(
xray_structure=xrs_adjacent_trimmed,
pdb_hierarchy=pdb_hierarchy,
selection=selection,
processed_pdb_file=None,
target_map=self.target_map,
geometry_restraints_manager=grm_adjacent_trimmed.geometry,
d_min=self.d_min,
out=null_out(),
debug=True)
# place sidechain using mmtbx.refinement.real_space.fit_residue
if ((atom_group.resname in rotatable_sidechain_atoms) and
(use_chi1_sampling)) :
fit_chi1_simple(
residue=box.only_residue(),
unit_cell=box.unit_cell_box,
target_map=box.target_map_box,
rotamer_eval=self.rotamer_eval)
box.update_sites_from_pdb_atoms()
else :
box.fit_residue_in_box(backbone_sample_angle=backbone_sample_angle)
if (anneal) :
box.anneal(start_temperature=annealing_temperature)
#box.real_space_refine()
sites_new = box.update_original_coordinates()
pdb_hierarchy.atoms().set_xyz(sites_new)
return building.atom_group_as_hierarchy(new_atom_group)
