schrodinger.protein.assignment module

Module for optimizing hydroxyl, thiol and water orientiations, Chi-flips of asparagine, glutamine and histidine, and protonation states of aspartic acid, glutamic acid, and histidine.

Usage: ProtAssign(st)

Copyright Schrodinger, LLC. All rights reserved.

exception schrodinger.protein.assignment.PropKaException(value)

Bases: Exception

__init__(value)

Initialize self. See help(type(self)) for accurate signature.

args
with_traceback()

Exception.with_traceback(tb) – set self.__traceback__ to tb and return self.

schrodinger.protein.assignment.report(message_level=1, message='')
schrodinger.protein.assignment.measure(ct, atom1=None, atom2=None, atom3=None, atom4=None, use_xtal=False, max_dist=10.0)
schrodinger.protein.assignment.calculate_interaction_matrix(ct, iatoms, distance, use_xtal=False)

Create an interaction matrix based on the changeable_index atom property

Parameters

  • ct (structure.Structure) – Structure with annotated atoms having set the i_pa_changeable_index corresponding the the index of the changeable

  • iatoms (List[int]) – List of atom indices which take part in interaction

  • distance (float) – Max distance between interacting atoms

  • use_xtal – Take into account crystal symmetry mates

  • use_xtal – bool

Returns

interaction matrix allowing double indexing: interact[i][j]

Return type

defaultdict(lambda: defaultdict(bool))

schrodinger.protein.assignment.annotate_structure_interactors(ct, acceptors, donors, clashers)

Set atom property for each interactor class

Parameters

  • ct (Structure) – Structure to annotate

  • acceptors (List[int]) – List of acceptor atom indices

  • donors (List[tuple[int, int]]) – List of donor pair atom indices

  • clashers (List[int]) – List of clasher atom indices

Returns

None but sets atom properties

Return type

NoneType

schrodinger.protein.assignment.check_residue_flip_state(res: schrodinger.structure._structure._Residue) → tuple

Determine whether a residue cannot be flipped, is, or is not flipped.

Parameters

res – a protein residue

Returns

a tuple of (state, msg), where state describes whether the residue is flipped (True), is not flipped (False), or cannot be flipped (None); if None, msg will contain an explanation

Return type

tuple[bool or NoneType, str]

schrodinger.protein.assignment.get_residue_flip_state(res: schrodinger.structure._structure._Residue) → Optional[bool]

Return the flip state of a protein residue.

A truncated version of check_residue_flip_state().

Parameters

res – a protein residue

Returns

the flip state of a residue

schrodinger.protein.assignment.get_residue_string(residue: schrodinger.structure._structure._Residue) → str

Return a string describing a residue.

The string will match the format

<chain>:<residue PDB code> <residue number>[<insertion code>]

Parameters

residue – a protein residue

Returns

a string describing the residue

schrodinger.protein.assignment.get_heavy_neighbors(atom: schrodinger.structure._structure._StructureAtom) → list
Parameters

atom – an atom

Returns

a list of heavy (non-H) atoms covalently bound to atom

Return type

list[structure._StructureAtom]

class schrodinger.protein.assignment.ProtAssign(ct, interactive=False, do_flips=True, asl='', noprot_asl='', atoms=[], use_xtal=False, torsion_penalty=False, sample_waters=True, sample_acids=True, freeze_existing=False, include_initial=False, max_comb=10000, num_sequential_cycles=30, max_cluster_size=None, logging_level=1, quiet_flag=False, debug_flag=False, add_labels=True, label_pkas=False, pH='neutral', use_propka=True, propka_pH=7.0, user_states=[], minimize=False)

Bases: object

class changeable(ct, iatom)

Bases: object

asl = 'none'
OH_length = 1.0
HOH_angle = 109.5
max_hbond_distance = 3.5
hbond_min_angle = 150.0
hbond_heavy_min_angle = 80.0
hbond_heavy_max_angle = 140.0
__init__(ct, iatom)

Initialize self. See help(type(self)) for accurate signature.

pre_treat_1(ct)
pre_treat_2(ct)
pre_treat(ct)
enumerate_states(ct, acceptors, donors, pH, do_flips=True, include_initial=False)
lock_protonation()
add_current_to_states(ct)
assign_state(ct, istate, add_labels=True, label_pkas=False, state_gap=None, verbose=False)
assign_state_gap(atom, state_gaps, report_gaps=True)

Write the Gap in energy between the lowest energy state and the state with different protonation states or heavy atom positions to the output ct :param atom: The atom that should have properties written to it :type atom:structure.StructureAtom :param state_gaps: The energy gaps between states for a given

changeable position.

Parameters

report_gaps (Boolean) – Whether to report the gaps to the log file as well

update_atom_indices(ct, new_indices)
get_new_index(ct, atom_index, new_indices)
get_view_atoms()
get_residue_name(ct, iatom)
get_atom_name(ct, iatom)
swap_atoms(ct, atom1, atom2)
get_penalty(istate)
get_adjustable_atoms()
change_pka(pka, propka_pH)
get_dihedral_atoms(ct, h)
get_close_interactors(ct, dcell)

Return acceptors, donors and clashers that are close to this changeable heavy atoms.

Parameters

  • ct (Structure) – Structure with annotated atoms signfying interaction class

  • dcell (DistanceCell) – Distance cell to query for neighboring atoms

Returns

List of acceptors, donor pairs, and clashers atom indices

Return type

tuple[list[int], list[tuple[int, int]], list[int]]

class amide_changeable(ct, iatom)

Bases: schrodinger.protein.assignment.ProtAssign.changeable

This is the primary amide -NH2 group of ASN and GLN residues.

asl = '((res.ptype "ASN " AND atom.ptype " CG ") OR (res.ptype "GLN " AND atom.ptype " CD "))'
__init__(ct, iatom)

Initialize self. See help(type(self)) for accurate signature.

pre_treat_1(ct)
pre_treat_2(ct)
enumerate_states(ct, acceptors, donors, pH, do_flips=True, include_initial=False)
assign_state(ct, istate, add_labels=True, label_pkas=False, state_gaps=None, verbose=False)
update_atom_indices(ct, new_indices)
get_heavies()
get_state_sites(ct, istate)
get_view_atoms()
get_penalty(istate)
get_adjustable_atoms()
HOH_angle = 109.5
OH_length = 1.0
add_current_to_states(ct)
assign_state_gap(atom, state_gaps, report_gaps=True)

Write the Gap in energy between the lowest energy state and the state with different protonation states or heavy atom positions to the output ct :param atom: The atom that should have properties written to it :type atom:structure.StructureAtom :param state_gaps: The energy gaps between states for a given

changeable position.

Parameters

report_gaps (Boolean) – Whether to report the gaps to the log file as well

change_pka(pka, propka_pH)
get_atom_name(ct, iatom)
get_close_interactors(ct, dcell)

Return acceptors, donors and clashers that are close to this changeable heavy atoms.

Parameters

  • ct (Structure) – Structure with annotated atoms signfying interaction class

  • dcell (DistanceCell) – Distance cell to query for neighboring atoms

Returns

List of acceptors, donor pairs, and clashers atom indices

Return type

tuple[list[int], list[tuple[int, int]], list[int]]

get_dihedral_atoms(ct, h)
get_new_index(ct, atom_index, new_indices)
get_residue_name(ct, iatom)
hbond_heavy_max_angle = 140.0
hbond_heavy_min_angle = 80.0
hbond_min_angle = 150.0
lock_protonation()
max_hbond_distance = 3.5
pre_treat(ct)
swap_atoms(ct, atom1, atom2)
class histidine_changeable(ct, iatom)

Bases: schrodinger.protein.assignment.ProtAssign.changeable

Imidazole group of Histidine residues.

asl = '((res.ptype "HIS ","HID ","HIE ","HIP ")) AND ((atom.ptype " CG "))'
__init__(ct, iatom)

Initialize self. See help(type(self)) for accurate signature.

pre_treat_1(ct)
pre_treat_2(ct)
enumerate_states(ct, acceptors, donors, pH, do_flips=True, include_initial=False)
lock_protonation()
assign_state(ct, istate, add_labels=True, label_pkas=False, state_gaps=None, verbose=False)
update_atom_indices(ct, new_indices)
get_heavies()
get_state_sites(ct, istate)
get_view_atoms()
get_penalty(istate)
get_adjustable_atoms()
change_pka(pka, propka_pH)
HOH_angle = 109.5
OH_length = 1.0
add_current_to_states(ct)
assign_state_gap(atom, state_gaps, report_gaps=True)

Write the Gap in energy between the lowest energy state and the state with different protonation states or heavy atom positions to the output ct :param atom: The atom that should have properties written to it :type atom:structure.StructureAtom :param state_gaps: The energy gaps between states for a given

changeable position.

Parameters

report_gaps (Boolean) – Whether to report the gaps to the log file as well

get_atom_name(ct, iatom)
get_close_interactors(ct, dcell)

Return acceptors, donors and clashers that are close to this changeable heavy atoms.

Parameters

  • ct (Structure) – Structure with annotated atoms signfying interaction class

  • dcell (DistanceCell) – Distance cell to query for neighboring atoms

Returns

List of acceptors, donor pairs, and clashers atom indices

Return type

tuple[list[int], list[tuple[int, int]], list[int]]

get_dihedral_atoms(ct, h)
get_new_index(ct, atom_index, new_indices)
get_residue_name(ct, iatom)
hbond_heavy_max_angle = 140.0
hbond_heavy_min_angle = 80.0
hbond_min_angle = 150.0
max_hbond_distance = 3.5
pre_treat(ct)
swap_atoms(ct, atom1, atom2)
class carboxyl_changeable(ct, iatom)

Bases: schrodinger.protein.assignment.ProtAssign.changeable

asl = '(res.ptype "ASP ","ASH " AND atom.ptype " CG ") OR (res.ptype "GLU ","GLH " AND atom.ptype " CD ")'
__init__(ct, iatom)

Initialize self. See help(type(self)) for accurate signature.

pre_treat_1(ct)
pre_treat_2(ct)
enumerate_states(ct, acceptors, donors, pH, do_flips=True, include_initial=False)
lock_protonation()
assign_state(ct, istate, add_labels=True, label_pkas=False, state_gaps=None, verbose=False)
update_atom_indices(ct, new_indices)
get_heavies()
get_state_sites(ct, istate)
get_view_atoms()
get_penalty(istate)
get_adjustable_atoms()
change_pka(pka, propka_pH)
HOH_angle = 109.5
OH_length = 1.0
add_current_to_states(ct)
assign_state_gap(atom, state_gaps, report_gaps=True)

Write the Gap in energy between the lowest energy state and the state with different protonation states or heavy atom positions to the output ct :param atom: The atom that should have properties written to it :type atom:structure.StructureAtom :param state_gaps: The energy gaps between states for a given

changeable position.

Parameters

report_gaps (Boolean) – Whether to report the gaps to the log file as well

get_atom_name(ct, iatom)
get_close_interactors(ct, dcell)

Return acceptors, donors and clashers that are close to this changeable heavy atoms.

Parameters

  • ct (Structure) – Structure with annotated atoms signfying interaction class

  • dcell (DistanceCell) – Distance cell to query for neighboring atoms

Returns

List of acceptors, donor pairs, and clashers atom indices

Return type

tuple[list[int], list[tuple[int, int]], list[int]]

get_dihedral_atoms(ct, h)
get_new_index(ct, atom_index, new_indices)
get_residue_name(ct, iatom)
hbond_heavy_max_angle = 140.0
hbond_heavy_min_angle = 80.0
hbond_min_angle = 150.0
max_hbond_distance = 3.5
pre_treat(ct)
swap_atoms(ct, atom1, atom2)
class rotatable_changeable(ct, iatom)

Bases: schrodinger.protein.assignment.ProtAssign.changeable

asl = '((res.ptype "CYS ","CYT ") AND (atom.ptype " SG ") AND (atom.formal -1)) OR ((res.ptype "TYR ") AND (atom.ptype " OH ") AND (atom.formal -1)) OR (( atom.ele H AND not /C0-H0/ AND not /N0-H0/ ) AND NOT (res.ptype "HOH","DOD","SPC","ASH","GLH","ASP","GLU" ))'
__init__(ct, iatom)

Initialize self. See help(type(self)) for accurate signature.

pre_treat_1(ct)
pre_treat_2(ct)
enumerate_states(ct, acceptors, donors, pH, do_flips=True, include_initial=False)
lock_protonation()
add_current_to_states(ct)
assign_state(ct, istate, add_labels=True, label_pkas=False, state_gaps=None, verbose=False)
update_atom_indices(ct, new_indices)
get_heavies()
get_state_sites(ct, istate)
get_view_atoms()
get_penalty(istate)
get_adjustable_atoms()
change_pka(pka, propka_pH)
HOH_angle = 109.5
OH_length = 1.0
assign_state_gap(atom, state_gaps, report_gaps=True)

Write the Gap in energy between the lowest energy state and the state with different protonation states or heavy atom positions to the output ct :param atom: The atom that should have properties written to it :type atom:structure.StructureAtom :param state_gaps: The energy gaps between states for a given

changeable position.

Parameters

report_gaps (Boolean) – Whether to report the gaps to the log file as well

get_atom_name(ct, iatom)
get_close_interactors(ct, dcell)

Return acceptors, donors and clashers that are close to this changeable heavy atoms.

Parameters

  • ct (Structure) – Structure with annotated atoms signfying interaction class

  • dcell (DistanceCell) – Distance cell to query for neighboring atoms

Returns

List of acceptors, donor pairs, and clashers atom indices

Return type

tuple[list[int], list[tuple[int, int]], list[int]]

get_dihedral_atoms(ct, h)
get_new_index(ct, atom_index, new_indices)
get_residue_name(ct, iatom)
hbond_heavy_max_angle = 140.0
hbond_heavy_min_angle = 80.0
hbond_min_angle = 150.0
max_hbond_distance = 3.5
pre_treat(ct)
swap_atoms(ct, atom1, atom2)
class amine_changeable(ct, iatom)

Bases: schrodinger.protein.assignment.ProtAssign.changeable

asl = '((res.ptype "LYS ","LYN ") AND (atom.ptype " NZ "))'
__init__(ct, iatom)

Initialize self. See help(type(self)) for accurate signature.

pre_treat_1(ct)
pre_treat_2(ct)
enumerate_states(ct, acceptors, donors, pH, do_flips=True, sample_neutral_states=False, include_initial=False)

Generate states for lysines.

States are generated by rotating hydrogens for acceptor/donor interactions and by optionally including the neutral state.

Parameters

  • ct (Structure) – Structure to generate states for

  • acceptors (List[int]) – List of acceptor atom indices

  • donors (List[(int, int)]) – List of donor atom indices

  • pH (float) – pH of system

  • do_flips (bool) – Does nothing

  • sample_neutral_states (bool) – Include neutral states. Since PROPKA’s pKa prediction is unreliable for Lys, currently we have no method of confidently assess whether it is neutral. So it’s turned off by default.

  • include_initial (bool) – Include the initial state of the Lys

lock_protonation()
assign_state(ct, istate, add_labels=True, label_pkas=False, state_gaps=None, verbose=False)
update_atom_indices(ct, new_indices)
get_heavies()
get_state_sites(ct, istate)
get_view_atoms()
get_penalty(istate)
change_pka(pka, propka_pH)
HOH_angle = 109.5
OH_length = 1.0
add_current_to_states(ct)
assign_state_gap(atom, state_gaps, report_gaps=True)

Write the Gap in energy between the lowest energy state and the state with different protonation states or heavy atom positions to the output ct :param atom: The atom that should have properties written to it :type atom:structure.StructureAtom :param state_gaps: The energy gaps between states for a given

changeable position.

Parameters

report_gaps (Boolean) – Whether to report the gaps to the log file as well

get_adjustable_atoms()
get_atom_name(ct, iatom)
get_close_interactors(ct, dcell)

Return acceptors, donors and clashers that are close to this changeable heavy atoms.

Parameters

  • ct (Structure) – Structure with annotated atoms signfying interaction class

  • dcell (DistanceCell) – Distance cell to query for neighboring atoms

Returns

List of acceptors, donor pairs, and clashers atom indices

Return type

tuple[list[int], list[tuple[int, int]], list[int]]

get_dihedral_atoms(ct, h)
get_new_index(ct, atom_index, new_indices)
get_residue_name(ct, iatom)
hbond_heavy_max_angle = 140.0
hbond_heavy_min_angle = 80.0
hbond_min_angle = 150.0
max_hbond_distance = 3.5
pre_treat(ct)
swap_atoms(ct, atom1, atom2)
class water_changeable(ct, iatom)

Bases: schrodinger.protein.assignment.ProtAssign.changeable

asl = '(water) AND (atom.ele O)'
redundancy_tolerance = 0.5
__init__(ct, iatom)

Initialize self. See help(type(self)) for accurate signature.

find_dihedrals(ct, atom1, atom2, atom3, acceptors, donors)
enumerate_states(ct, acceptors, donors, pH, do_flips=True, include_initial=False)
add_current_to_states(ct)
assign_state(ct, istate, add_labels=True, label_pkas=False, state_gaps=None, verbose=False)
update_atom_indices(ct, new_indices)
get_heavies()
get_state_sites(ct, istate)
get_view_atoms()
get_penalty(istate)
get_adjustable_atoms()
HOH_angle = 109.5
OH_length = 1.0
assign_state_gap(atom, state_gaps, report_gaps=True)

Write the Gap in energy between the lowest energy state and the state with different protonation states or heavy atom positions to the output ct :param atom: The atom that should have properties written to it :type atom:structure.StructureAtom :param state_gaps: The energy gaps between states for a given

changeable position.

Parameters

report_gaps (Boolean) – Whether to report the gaps to the log file as well

change_pka(pka, propka_pH)
get_atom_name(ct, iatom)
get_close_interactors(ct, dcell)

Return acceptors, donors and clashers that are close to this changeable heavy atoms.

Parameters

  • ct (Structure) – Structure with annotated atoms signfying interaction class

  • dcell (DistanceCell) – Distance cell to query for neighboring atoms

Returns

List of acceptors, donor pairs, and clashers atom indices

Return type

tuple[list[int], list[tuple[int, int]], list[int]]

get_dihedral_atoms(ct, h)
get_new_index(ct, atom_index, new_indices)
get_residue_name(ct, iatom)
hbond_heavy_max_angle = 140.0
hbond_heavy_min_angle = 80.0
hbond_min_angle = 150.0
lock_protonation()
max_hbond_distance = 3.5
pre_treat(ct)
pre_treat_1(ct)
pre_treat_2(ct)
swap_atoms(ct, atom1, atom2)
class hbond_cluster

Bases: object

get_residue_name(ct, iatom)
get_atom_name(ct, iatom)
__init__()

Initialize self. See help(type(self)) for accurate signature.

setup_xtal(ct, interact, clustering_distance)
optimize(ct, interact, static_donors, static_acceptors, static_clashers, max_comb, num_sequential_cycles, use_propka, propka_pH=7.0, xtal_ct=None)
score_combination(ct, interact, states)
single_point(ct, interact, static_donors, static_acceptors, static_clashers, xtal_ct=None)
setup_local_static_alt(ct, static_acceptors, static_donors, static_clashers)
setup_local_static(ct, static_acceptors, static_donors, static_clashers)
initialize_score_storage()
pre_score_self(ct)
pre_score_pairs(ct, interact)
score_pair(ct, iacceptors, idonors, iclashers, icharge, jacceptors, jdonors, jclashers, jcharge, use_xtal=False)
score_donor_acceptor(ct, donor_heavy, donor_hydrogen, acceptor_heavy, use_xtal=False)
score_donor_donor(ct, donor1_heavy, donor1_hydrogen, donor2_heavy, donor2_hydrogen, use_xtal=False)
score_exhaustively(ct, interact, find_all_solutions=True, tolerate_clashes=False)
score_sequentially(ct, interact, num_sequential_cycles)

This routine uses an algorithm similar to Prime’s iteration to convergence. Starting from a random configuration, each species is optimized in turn, keeping the others fixed in their current state. This continues until the system reaches convergence (no more changes in the most optimal state for all residues).

Parameters

  • ct (schrodigner.Structure) – input/output structure, will be modified

  • interact –

    ??

  • num_sequential_cycles (int) – Number of cycles of randomization and optimization to conduct

expand_solutions(ct, interact)

This takes an existing set of good solutions and generates more by deconverging them and then iterating them back to convergence. Generates at least 10 new solutions.

recombine_solutions(ct, interact)

This is similar to score_sequentially, but begins with some pre-existing good solutions in self.combinations, and then creates hybrids to try to improve on them.

deconverge(ct, interact, comb, problem_cutoff=50.0)

This starts with what is assumed to be a good solution, and then randomizes the states, but not to anything that produces a problem.

iterate_to_convergence(ct, interact, comb, problem_cutoff=50.0)

This iterates the combination ‘comb’ to convergence. Maximum of 10 cycles.

create_hybrid(local_combinations, interact, random_scaffold=False)

This takes the lowest energy solution, and for each problematic region it searches other solutions (in random order) for any which may have had better luck for just that part of the overall cluster. It then splices those solutions into the lowest energy one. If random_scaffold, then it selects a random solution as the basis in stead of the lowest energy one.

trim_redundant_combinations()
assign_combination(ct, icombination, add_labels, label_pkas, verbose=False)

Assign a given combination to this cluster :param ct: The structure to operate on :type ct:schrodinger.Structure :param icombination: The index of the combination to assign

or if this number is larger then the stored combinations, just keep the current state

:param add_labels:Whether to add labels to atoms to be

seen in maestro with the current protonation state

:type add_labels:Boolean :param label_pka:Whether to add labels for the pKa of each

residue

:type label_pka:Boolean :param verbose:Whether to report additional information

to the log file about the combination chosen

:type verbose:Boolean

determine_gap(icombination, ichangeable)

Create a dictionary with the energy gaps to each of the various states. States that differ by only a hydrogen rotation are not considered unique :type icombination: integer :param icombination: the combination to use as the zero

point. In most situations this will be the lowest energy combination ( 0 when sorted)

Parameters

ichangeable (integer) – The residue number ( or position number) within the cluster which will be analyzed

Rparam

dictionary where the key is the name of the state or “Default” when the state is one of the staggers

Return type

dictionary with a key of string and value of a float

__init__(ct, interactive=False, do_flips=True, asl='', noprot_asl='', atoms=[], use_xtal=False, torsion_penalty=False, sample_waters=True, sample_acids=True, freeze_existing=False, include_initial=False, max_comb=10000, num_sequential_cycles=30, max_cluster_size=None, logging_level=1, quiet_flag=False, debug_flag=False, add_labels=True, label_pkas=False, pH='neutral', use_propka=True, propka_pH=7.0, user_states=[], minimize=False)

Initialize self. See help(type(self)) for accurate signature.

fix_elements(ct)
freeze_existing_hydrogens(ct)
setup(ct)
remove_zero_order_bonds(ct)
extend_targeted_to_hyds(ct)
delete_atoms(ct, atoms)
run_propka(changeables, ct, use_xtal=False)
generate_mates(ct)
apply_pkas(changeables, changes, propka_pH)
find_protonation_state_changes(ct, clusters='all')
identify_species(ct)
identify_all_hbonders(ct)
enumerate_changeable_states(ct)
lock_protonation_states(ct)
remove_changeables_from_hbonders()
cluster(ct)

Cluster changeables based on their heavies.

set_user_states(ct)
assign_state_of_changeable(ct, ichangeable, istate)
increment_state_of_changeable(ct, ichangeable)
decrement_state_of_changeable(ct, ichangeable)
record_current_indices(ct)
assign_best_combinations(ct, last_time=False)

Assign the best combinations to the ct and report output :param ct:The structure to operate on :type ct: schrodinger.Structure :param last_time: Whether or not this is the last time through

when we should be extra verbose

assign_cluster_combination(ct, icluster, icombination)
single_point_cluster(ct, icluster)
optimize_cluster(ct, icluster, assign=True)
optimize(ct)
minimize_hydrogens(ct)
restore_zobs(ct)
cleanup(ct)
summarize_pkas()