"""
Functions to infer structural data such as missing atom coordinates, bond connectivity, or atom labels.
"""
import re
from typing import Union
import pandas as pd
import networkx as nx
from collections import defaultdict
import warnings
import numpy as np
from scipy.spatial.distance import cdist
from Bio.PDB import NeighborSearch
import periodictable as pt
import buildamol.utils.ic as _ic
import buildamol.utils.defaults as defaults
import buildamol.resources as resources
import buildamol.structural.base as base
import buildamol.structural.neighbors as neighbors
import buildamol.structural.geometry as geometry
import buildamol.utils.auxiliary as aux
# might cause circular imports!
import buildamol.base_classes as base_classes
element_connectivity = {
"C": 4,
"H": 1,
"O": 2,
"N": 3,
"S": 2,
"P": 5,
"F": 1,
"Cl": 1,
"Br": 1,
"I": 1,
"B": 3,
"Si": 4,
"Se": 2,
"Zn": 2,
"Ca": 2,
"Mg": 2,
"Fe": 2,
"Cu": 1,
"Mn": 2,
}
element_to_hydrogen_bond_lengths = {
"C": 1.09,
"N": 1.01,
"O": 0.96,
"S": 1.04,
"P": 1.10,
"F": 0.92,
"Cl": 0.99,
"Br": 1.14,
"I": 1.33,
"B": 1.19,
"Si": 1.17,
"Se": 1.17,
"Zn": 1.31,
"Ca": 1.74,
"Mg": 1.36,
"Fe": 1.24,
"Cu": 1.28,
"Mn": 1.20,
}
single_bond_lengths = {
"C": {
"C": 1.54,
"N": 1.47,
"O": 1.43,
"S": 1.81,
"P": 1.87,
"F": 1.35,
"Cl": 1.77,
"Br": 1.94,
"I": 2.14,
"H": 1.09,
},
"N": {
"C": 1.47,
"N": 1.45,
"O": 1.43,
"S": 1.81,
"P": 1.87,
"F": 1.35,
"Cl": 1.77,
"Br": 1.94,
"I": 2.14,
"H": 1.01,
},
"O": {
"C": 1.43,
"N": 1.43,
"O": 1.34,
"S": 1.81,
"P": 1.87,
"F": 1.35,
"Cl": 1.77,
"Br": 1.94,
"I": 2.14,
"H": 0.96,
},
"S": {
"C": 1.81,
"N": 1.81,
"O": 1.81,
"S": 2.05,
"P": 2.05,
"F": 1.81,
"Cl": 2.05,
"Br": 2.05,
"I": 2.05,
"H": 1.04,
},
"P": {
"C": 1.87,
"N": 1.87,
"O": 1.87,
"S": 2.05,
"P": 2.05,
"F": 1.87,
"Cl": 2.05,
"Br": 2.05,
"I": 2.05,
"H": 1.10,
},
"F": {
"C": 1.35,
"N": 1.35,
"O": 1.35,
"S": 1.81,
"P": 1.87,
"F": 1.35,
"Cl": 1.77,
"Br": 1.94,
"I": 2.14,
"H": 0.92,
},
"Cl": {
"C": 1.77,
"N": 1.77,
"O": 1.77,
"S": 2.05,
"P": 2.05,
"F": 1.77,
"Cl": 2.05,
"Br": 2.05,
"I": 2.05,
"H": 0.99,
},
"Br": {
"C": 1.94,
"N": 1.94,
"O": 1.94,
"S": 2.05,
"P": 2.05,
"F": 1.94,
"Cl": 2.05,
"Br": 2.05,
"I": 2.05,
"H": 1.14,
},
"I": {
"C": 2.14,
"N": 2.14,
"O": 2.14,
"S": 2.05,
"P": 2.05,
"F": 2.14,
"Cl": 2.05,
"Br": 2.05,
"I": 2.05,
"H": 1.33,
},
"H": {
"C": 1.09,
"N": 1.01,
"O": 0.96,
"S": 1.04,
"P": 1.10,
"F": 0.92,
"Cl": 0.99,
"Br": 1.14,
"I": 1.33,
},
}
double_bond_lengths = {
"C": {
"C": 1.34,
"N": 1.30,
"O": 1.21,
"S": 2.05,
"P": 2.05,
"F": 1.34,
"Cl": 2.05,
"Br": 2.05,
"I": 2.05,
},
"N": {
"C": 1.30,
"N": 1.28,
"O": 1.21,
"S": 2.05,
"P": 2.05,
"F": 1.30,
"Cl": 2.05,
"Br": 2.05,
"I": 2.05,
},
"O": {
"C": 1.21,
"N": 1.21,
"O": 1.20,
"S": 2.05,
"P": 2.05,
"F": 1.21,
"Cl": 2.05,
"Br": 2.05,
"I": 2.05,
},
"S": {
"C": 2.05,
"N": 2.05,
"O": 2.05,
"S": 2.28,
"P": 2.28,
"F": 2.05,
"Cl": 2.28,
"Br": 2.28,
"I": 2.28,
},
"P": {
"C": 2.05,
"N": 2.05,
"O": 2.05,
"S": 2.28,
"P": 2.28,
"F": 2.05,
"Cl": 2.28,
"Br": 2.28,
"I": 2.28,
},
"F": {
"C": 1.34,
"N": 1.30,
"O": 1.21,
"S": 2.05,
"P": 2.05,
"F": 1.34,
"Cl": 2.05,
"Br": 2.05,
"I": 2.05,
},
"Cl": {
"C": 2.05,
"N": 2.05,
"O": 2.05,
"S": 2.28,
"P": 2.28,
"F": 2.05,
"Cl": 2.28,
"Br": 2.28,
"I": 2.28,
},
"Br": {
"C": 2.05,
"N": 2.05,
"O": 2.05,
"S": 2.28,
"P": 2.28,
"F": 2.05,
"Cl": 2.28,
"Br": 2.28,
"I": 2.28,
},
"I": {
"C": 2.05,
"N": 2.05,
"O": 2.05,
"S": 2.28,
"P": 2.28,
"F": 2.05,
"Cl": 2.28,
"Br": 2.28,
"I": 2.28,
},
}
triple_bond_lengths = {
"C": {
"C": 1.20,
"N": 1.16,
"O": 1.13,
"S": 2.05,
"P": 2.05,
"F": 1.20,
"Cl": 2.05,
"Br": 2.05,
"I": 2.05,
},
"N": {
"C": 1.16,
"N": 1.14,
"O": 1.13,
"S": 2.05,
"P": 2.05,
"F": 1.16,
"Cl": 2.05,
"Br": 2.05,
"I": 2.05,
},
"O": {
"C": 1.13,
"N": 1.13,
"O": 1.12,
"S": 2.05,
"P": 2.05,
"F": 1.13,
"Cl": 2.05,
"Br": 2.05,
"I": 2.05,
},
"S": {
"C": 2.05,
"N": 2.05,
"O": 2.05,
"S": 2.51,
"P": 2.51,
"F": 2.05,
"Cl": 2.51,
"Br": 2.51,
"I": 2.51,
},
"P": {
"C": 2.05,
"N": 2.05,
"O": 2.05,
"S": 2.51,
"P": 2.51,
"F": 2.05,
"Cl": 2.51,
"Br": 2.51,
"I": 2.51,
},
"F": {
"C": 1.20,
"N": 1.16,
"O": 1.13,
"S": 2.05,
"P": 2.05,
"F": 1.20,
"Cl": 2.05,
"Br": 2.05,
"I": 2.05,
},
}
bond_length_by_order = {
1: single_bond_lengths,
2: double_bond_lengths,
3: triple_bond_lengths,
}
acceptable_surplus_charge = 5
"""
The maximum allowed positive charge that can be left on an atom
if no hydrogens can be further removed to balance the charge.
This is used in `change_element` to prevent the creation of
unrealistically charged atoms and thereby unlikely structures.
"""
[docs]
def atomic_number(element: str):
"""
Get the atomic number of an element.
Parameters
----------
element : str
The element symbol.
Returns
-------
int
The atomic number of the element.
"""
return pt.elements.symbol(element.title()).number
[docs]
class AutoLabel:
"""
A automatic atom labeller
Parameters
----------
atom_graph : nx.Graph
The molecule's atom graph
"""
def __init__(self, atom_graph):
self.graph = atom_graph
self._bond_orders = nx.get_edge_attributes(self.graph, "bond_order")
self._cycles = nx.cycle_basis(self.graph)
self._df_all = self._make_df()
self._df = None
self._element_counter = defaultdict(int)
@property
def carbons(self):
"""
All carbon atoms in the molecule.
"""
return [n for n in self.graph.nodes if n.element == "C"]
[docs]
def autolabel(self):
"""
Generate labels for the atoms in the molecule
Returns
-------
pd.DataFrame
A dataframe with the atom objects and their new labels.
"""
for res_df in self._df_all.groupby("residue"):
self._df = res_df[1]
self._parse_carbon_labels()
self._parse_hetero_labels()
self._parse_hydrogen_labels()
self._df["label"] = self._df["element"] + self._df["label"]
self._final_vet()
self._df_all.loc[self._df.index, "label"] = self._df["label"]
return self._df_all[["atom", "label"]]
[docs]
@staticmethod
def hydrogen_neighbors(atom):
"""
Generate automated labels for an atom's possible hydrogen neighbors.
Parameters
----------
atom : Atom
The atom
Returns
-------
list
A list of possible hydrogen labels
Examples
--------
>>> from buildamol import Atom
>>> a = Atom(id="C1")
>>> AutoLabel.hydrogen_neighbors(a)
['H1', 'H11', 'H12', 'H13', 'H14']
>>> a = Atom(id="OXT")
>>> AutoLabel.hydrogen_neighbors(a)
['HOXT', 'HOXT1', 'HOXT2']
"""
connectivity = element_connectivity.get(atom.element, 0)
if atom.element == "C":
return [
f"H{atom.id[1:]}",
*(f"H{atom.id[1:]}{i+1}" for i in range(connectivity)),
]
return [f"H{atom.id}", *(f"H{atom.id}{i+1}" for i in range(connectivity))]
def _neighbors(self, atoms):
"""
Get the neighbors of a list of atoms.
"""
neighbors = []
neighbor_element_sum = []
for atom in atoms:
ndx = 0
edx = 0
for neighbor in self.graph.neighbors(atom):
ndx += 1
n_num = pt.elements.symbol(neighbor.element.title()).number
if n_num != 1 and n_num != 6:
n_num *= 10
n_num *= self._bond_orders.get((atom, neighbor), 1)
edx += n_num
neighbors.append(ndx)
neighbor_element_sum.append(edx)
return neighbors, neighbor_element_sum
def _in_cycle(self, atom):
"""
Check if a list of atoms is in a cycle.
"""
for cycle in self._cycles:
if set(atom).issubset(cycle):
return True
return False
def _make_df(self):
"""
Make a dataframe of the molecule connectivity.
"""
neighbors, neighbor_element_sum = self._neighbors(self.graph.nodes)
in_cycle = [self._in_cycle([a]) for a in self.graph.nodes]
self._df = pd.DataFrame(
{
"atom": list(self.graph.nodes),
"element": [a.element.title() for a in self.graph.nodes],
"neighbors": neighbors,
"neighbor_element_sum": neighbor_element_sum,
"in_cycle": in_cycle,
"residue": [a.get_parent().id[1] for a in self.graph.nodes],
}
)
self._df["total"] = (
self._df.neighbors
* self._df.neighbor_element_sum
* (10 * self._df.in_cycle + 1)
)
self._df["label"] = "none"
return self._df
def _parse_c1(self, carbons=None):
if carbons is not None:
carbons = self._df[self._df.atom.isin(carbons)]
else:
carbons = self._df[self._df.element == "C"]
carbons = carbons[carbons.label == "none"]
carbons = carbons.sort_values("total", ascending=False)
# carbons = carbons.sort_values(
# ["neighbors", "neighbor_element_sum"], ascending=False
# )
carbons = carbons.reset_index(drop=True)
return carbons.atom[0]
def _parse_c_next(self, c_current):
neighbors = self.graph.neighbors(c_current)
neighbors = self._df[self._df.atom.isin(neighbors)]
neighbors = neighbors[neighbors.element == "C"]
neighbors = neighbors[neighbors.label == "none"]
neighbors = neighbors.sort_values("total", ascending=False)
# neighbors = neighbors.sort_values(
# ["neighbors", "neighbor_element_sum"], ascending=False
# )
neighbors = neighbors.reset_index(drop=True)
if len(neighbors) == 0:
return None
return neighbors.atom[0]
def _parse_carbon_labels(self):
c1 = self._parse_c1()
self._df.loc[self._df.atom == c1, "label"] = "1"
self._c1_row = self._df[self._df.atom == c1]
idx = 2
c_current = c1
carbons = self._df[self._df.element == "C"]
while (carbons.label == "none").any():
c_next = self._parse_c_next(c_current)
if c_next is None:
c_next = self._parse_c1(carbons=carbons[carbons.label == "none"].atom)
self._df.loc[self._df.atom == c_next, "label"] = f"{idx}"
idx += 1
c_current = c_next
carbons = self._df[self._df.element == "C"]
def _parse_hetero_labels(self):
_neighbor_connect_dict = {}
heteros = self._df[(self._df.element != "C") * (self._df.element != "H")]
while (heteros.label == "none").any():
for hetero in heteros.atom:
neighbors = self.graph.neighbors(hetero)
neighbors = self._df[self._df.atom.isin(neighbors)]
# remove c1 row
if (
len(neighbors[(neighbors.element != "H")]) > 1
and len(neighbors[neighbors.element == "C"]) > 1
):
neighbors = neighbors[neighbors.atom != self._c1_row.atom.iloc[0]]
neighbors = neighbors[neighbors.label != "none"]
if len(neighbors[neighbors.element == "C"]) > 0:
neighbors = neighbors[neighbors.element == "C"]
use_blank_label = True
else:
use_blank_label = False
# used to by: sort by "label", and ascending=False
neighbors = neighbors.sort_values("total", ascending=True)
neighbors = neighbors.reset_index(drop=True)
if len(neighbors) == 0:
continue
neighbor = neighbors.atom.iloc[-1]
label = neighbors.label.iloc[-1]
if neighbor.element not in _neighbor_connect_dict:
_neighbor_connect_dict[neighbor] = {hetero.element: [hetero]}
else:
_neighbor_connect_dict[neighbor][hetero.element].append(hetero)
if not use_blank_label:
self._element_counter[hetero.element] += 1
if not label[-1].isdigit():
label = label[:-1]
label += chr(self._element_counter[hetero.element] + 64)
self._df.loc[self._df.atom == hetero, "label"] = label
heteros = self._df[(self._df.element != "C") * (self._df.element != "H")]
for _heteros in _neighbor_connect_dict.values():
if len(_heteros) > 1:
# idx = 1
for h in _heteros.values():
for idx, atom in enumerate(h):
self._df.loc[self._df.atom == h, "label"] += str(idx + 1)
# idx += 1
def _parse_hydrogen_labels(self):
_neighbor_connect_dict = {}
_hydrogen_unique_label_dict = {}
hydrogens = self._df[self._df.element == "H"]
for hydrogen in hydrogens.atom:
neighbors = self.graph.neighbors(hydrogen)
neighbors = self._df[self._df.atom.isin(neighbors)]
neighbors = neighbors[neighbors.label != "none"]
neighbors = neighbors.sort_values("label", ascending=False)
# neighbors = neighbors.sort_values(
# ["neighbors", "neighbor_element_sum"], ascending=False
# )
neighbors = neighbors.reset_index(drop=True)
if len(neighbors) == 0:
continue
neighbor = neighbors.atom.iloc[-1]
if neighbor not in _neighbor_connect_dict:
_neighbor_connect_dict[neighbor] = [hydrogen]
else:
_neighbor_connect_dict[neighbor].append(hydrogen)
element = neighbors.element.iloc[-1]
if element == "C":
element = ""
label = element + neighbors.label.iloc[-1]
mask = self._df.atom == hydrogen
self._df.loc[mask, "label"] = label
for neighbor, _hydrogens in _neighbor_connect_dict.items():
if len(_hydrogens) == 1:
continue
idx = 1
for h in _hydrogens:
mask = self._df.atom == h
if len(self._df.loc[mask, "label"].values[0]) >= 2:
ref = str(self._df.loc[mask, "label"].str[:2].values[0])
_hydrogen_unique_label_dict[ref] = (
_hydrogen_unique_label_dict.get(ref, 0) + 1
)
self._df.loc[mask, "label"] = ref + chr(
64 + _hydrogen_unique_label_dict[ref]
)
else:
self._df.loc[mask, "label"] += str(idx)
# new = self._df.loc[mask, "label"] + str(idx)
# self._df.loc[mask, "label"] += str(idx)
# self._df.loc[mask, "label"] = self._df.loc[mask, "label"].str[
# :2
# ] + chr(64 + idx)
idx += 1
def _final_vet(self):
_label_counts = self._df.label.value_counts()
_label_counts = _label_counts[_label_counts > 1]
_label_counts = _label_counts.sort_index()
_label_counts = _label_counts.reset_index()
_label_counts.columns = ["label", "count"]
_label_counts = _label_counts.sort_values("count", ascending=False)
_label_counts = _label_counts.reset_index(drop=True)
for idx in range(len(_label_counts)):
label = _label_counts.label.iloc[idx]
count = _label_counts["count"].iloc[idx]
atoms = self._df[self._df.label == label].atom
for j, atom in enumerate(atoms):
self._df.loc[self._df.atom == atom, "label"] += str(j + 1)
[docs]
def autolabel(molecule):
"""
Automatically relabel atoms in a structure to match the CHARMM naming scheme.
Note, this function is not guaranteed to produce the correct labels in all cases,
validation of the labels is recommended.
Parameters
----------
molecule : buildamol.core.Molecule
The molecule that holds the atoms to be relabeled.
This molecule needs to have bonds assigned or computed.
"""
labeler = AutoLabel(molecule._AtomGraph)
df = labeler.autolabel()
# df.loc[:, "residue"] = df.atom.apply(lambda x: x.get_parent())
# _ = df.residue.apply(lambda x: x.child_dict.clear())
for idx in range(len(df)):
atom = df.atom.iloc[idx]
label = df.label.iloc[idx]
# p = df.residue.iloc[idx]
# p.child_dict[label] = atom
atom.id = label
atom.name = label
return molecule
[docs]
def autolabel_atoms(bonds, to_label):
"""
Automatically relabel a list of atoms to match the CHARMM naming scheme.
Note, this function is not guaranteed to produce the correct labels in all cases,
validation of the labels is recommended.
Parameters
----------
bonds : list
A list of Bond objects that define the connectivity of atoms relevant for the labelling.
to_label : list
A list of Atom objects to relabel. This must be a subset of the atoms present in the bonds.
Returns
-------
dict
A dictionary mapping the original Atom objects to their new labels.
"""
from buildamol.graphs import AtomGraph
edges = [bond.to_tuple() for bond in bonds]
g = AtomGraph("autolabel_temp_graph", bonds=bonds)
labeler = AutoLabel(g)
df = labeler.autolabel()
label_dict = {}
for idx in range(len(df)):
atom = df.atom.iloc[idx]
label = df.label.iloc[idx]
if atom in to_label:
label_dict[atom] = label
return label_dict
[docs]
class Hydrogenator:
"""
A class to automatically add hydrogen atoms to organic molecules.
Note
----
This is designed specifically to infer hydrogens for organic molecules.
So it can infer hydrogen coordinates for CHNOPS atoms, but may not work reliably for non organic molecules.
"""
tetrahedral = geometry.Tetrahedral()
trigonal_planar = geometry.TrigonalPlanar()
linear = geometry.Linear()
__geometries__ = {
(1, 4): tetrahedral,
(1, 3): tetrahedral,
(1, 2): trigonal_planar,
(2, 3): trigonal_planar,
(2, 4): trigonal_planar,
(3, 4): linear,
(2, 5): tetrahedral, # an organic phosphate
}
# some default bond length for hydrogen atoms
_bond_length = 1.05
[docs]
def infer_hydrogens(
self, molecule: "Molecule", bond_length: float = 1
) -> "Molecule":
"""
Add hydrogen atoms to a molecule.
Parameters
----------
molecule : buildamol.core.Molecule
The molecule to add hydrogen atoms to.
bond_length : float
The bond length to use for the hydrogen atoms.
Returns
-------
Molecule
The molecule with hydrogen atoms added.
"""
self._molecule = molecule
self._bond_length = bond_length
for atom in self._molecule._atoms:
if atom.element == "H":
continue
connectivity = element_connectivity.get(atom.element, 0)
if connectivity == 0:
continue
bonds = self._molecule.get_bonds(atom)
free_slots = (
connectivity - sum(b.order for b in bonds) - (atom.pqr_charge or 0)
)
if free_slots > 0:
neighbors = set(j for i in bonds for j in i if j != atom)
self._add_hydrogens(
atom=atom,
neighbors=neighbors,
free_slots=free_slots,
bond_order=max(i.order for i in bonds),
connectivity=connectivity,
)
return self._molecule
[docs]
def add_hydrogens(self, atom, _molecule=None):
"""
Add hydrogens to one particular atom.
"""
self._molecule = _molecule or self._molecule
connectivity = element_connectivity.get(atom.element, 0)
if connectivity == 0:
return
bonds = self._molecule.get_bonds(atom)
free_slots = connectivity - sum(b.order for b in bonds) - (atom.pqr_charge or 0)
if free_slots > 0:
neighbors = set(j for i in bonds for j in i if j != atom)
self._add_hydrogens(
atom=atom,
neighbors=neighbors,
free_slots=free_slots,
bond_order=max(i.order for i in bonds),
connectivity=connectivity,
)
def _add_hydrogens(self, atom, neighbors, free_slots, bond_order, connectivity):
"""
Add hydrogen atoms to a molecule.
Parameters
----------
atom : Atom
The atom to add hydrogen atoms to.
neighbors : set
The eighbors the atom has.
free_slots : int
The number of free slots the atom has.
bond_order : int
The highest bond order of all bonds that connects the atom to a neighbor.
connectivity: int
The theoretically possible number of bonds the atom can form.
Returns
-------
list
A list of hydrogen atoms.
list
A list of bonds to the atom for each hydrogen.
"""
geometry = Hydrogenator.__geometries__.get((bond_order, connectivity), None)
if geometry is None:
return
_neighbors = list(neighbors)[: geometry.max_points - 1]
out = geometry.make_coords(atom, *_neighbors, length=self._bond_length)[
len(_neighbors) :
]
labels = AutoLabel.hydrogen_neighbors(atom)
if free_slots > 1:
labels.pop(0)
# technically this is convenient because
# it ensures that we don't have multiple Hs
# with the same id present
# labels = list(set(labels) - set(i.id for i in neighbors))
# now figure out which of the coordinates already belong to a neighbor
# and filter for the free locations
if len(out) > 1:
neighbor_coords = np.array([i.coord for i in neighbors])
d = cdist(out, neighbor_coords)
out = [out[i] for i in range(len(out)) if not np.any(d[i] < 0.95)]
if len(out) < free_slots:
raise ValueError(
f"Could not add the correct number of hydrogen atoms to {atom}! Expected {free_slots}, got {len(out)}."
)
Hs = [
base_classes.Atom(labels[i], out[i], element="H") for i in range(free_slots)
]
bonds = [base_classes.Bond(atom, H, 1) for H in Hs]
# now adjust the bond lengths to match the elements
length = element_to_hydrogen_bond_lengths.get(atom.element, self._bond_length)
for b in bonds:
base.adjust_bond_length(b, length)
self._molecule.add_atoms(*Hs, residue=atom.parent)
self._molecule.add_bonds(*bonds)
[docs]
def adjust_protonation(molecule, atom, new_charge):
"""
Adjust the protonation state of an atom in a molecule.
Parameters
----------
molecule : Molecule
The molecule to adjust the protonation state in.
atom : Atom
The atom to adjust the protonation state of.
new_charge : int
The new charge of the atom.
"""
if new_charge == atom.pqr_charge:
return
connectivity = element_connectivity.get(atom.element, 0)
if connectivity == 0:
raise ValueError(
f"Cannot adjust protonation state of {atom}. No connectivity information available for element {atom.element}."
)
if new_charge >= 0:
H = Hydrogenator()
if new_charge == 0:
# remove all hydrogens
hydrogens = molecule.get_hydrogens(atom)
molecule.remove_atoms(*hydrogens)
atom.pqr_charge = new_charge
H.add_hydrogens(atom, molecule)
else:
# little hack here
element_connectivity[atom.element] += new_charge
H.add_hydrogens(atom, molecule)
atom.pqr_charge = new_charge
element_connectivity[atom.element] = connectivity
else:
hydrogens = tuple(molecule.get_hydrogens(atom))
if len(hydrogens) < abs(new_charge):
raise ValueError(
f"Cannot adjust protonation state of {atom} to {new_charge}. Not enough hydrogens present."
)
molecule.remove_atoms(*hydrogens[: abs(new_charge)])
atom.pqr_charge = new_charge
return molecule
[docs]
def adjust_to_ph(
molecule, ph: Union[float, int, tuple], inplace: bool = True, **kwargs
):
"""
Adjust the protonation state of a molecule to suit a specific pH range
Note
----
This requires that `rdkit` and `molscrub` packages are installed!
Parameters
----------
molecule : Molecule
The molecule to adjust the protonation state in.
ph : Union(float, int, tuple)
The pH value or range of pH values to adjust the protonation state to.
If a single value is provided, the molecule will be adjusted to that pH.
If a tuple is provided, the molecule will be adjusted to the pH range (low, high)
inplace : bool
Whether to adjust the molecule inplace or return a new molecule.
**kwargs
Any keyword arguments to pass to the `molscrub.Scrub` class.
Returns
-------
Molecule
The molecule with the adjusted protonation state
"""
if not (
aux.has_package("scrubber") or aux.has_package("molscrub")
) or not aux.has_package("rdkit"):
raise ImportError(
"The `molscrub` and `rdkit` packages are required for this function."
)
if not inplace:
molecule = molecule.copy()
mol = molecule.remove_hydrogens().to_rdkit()
if isinstance(ph, (float, int)):
pH_low = ph
pH_high = None
elif isinstance(ph, (tuple, list, np.ndarray)):
pH_low, pH_high = ph
else:
raise ValueError(
f"Invalid pH value or range provided. Expected float, int, or tuple, got {type(pH)}."
)
if aux.has_package("scrubber"):
from scrubber import Scrub
elif aux.has_package("molscrub"):
from molscrub import Scrub
else:
raise ImportError("The `molscrub` package not found in the environment.")
skip_tautomers = kwargs.pop("skip_tautomers", True)
scrub = Scrub(
ph_high=pH_high, ph_low=pH_low, skip_tautomers=skip_tautomers, **kwargs
)
out = scrub(mol)
if len(out) == 0:
raise ValueError(
"Could not adjust the protonation state of the molecule. Try a different pH value or range or manually run the molecule through `molscrub` to investigate potential error sources."
)
if len(out) > 1:
_out = []
for i in out:
_out.append(molecule.__class__.from_rdkit(i))
out = _out
for i in out:
i.id = molecule.id
else:
out = molecule.__class__.from_rdkit(out[0])
molecule._base_struct = out._base_struct
molecule._model = out._model
molecule._bonds = out._bonds
molecule._AtomGraph = out._AtomGraph
out = molecule
return out
[docs]
def relabel_hydrogens(molecule):
"""
Relabel hydrogen atoms in a structure to match the CHARMM naming scheme.
Parameters
----------
molecule : buildamol.structural.base.Molecule
The molecule that holds the atoms to be relabeled.
This molecule needs to have bonds assigned or computed.
"""
_neighbors_H_dict = {}
for atom in molecule.get_atoms():
if not atom.element == "H":
continue
_neighbors = molecule.get_neighbors(atom)
if len(_neighbors) != 1:
Warning(
f"Atom {atom} (full_id: {atom.full_id}) has {len(_neighbors)} neighbors, but should have 1!"
)
continue
_neighbor = _neighbors.pop()
_neighbors_H_dict.setdefault(_neighbor, []).append(atom)
# ------------------------- IMPORTANT -------------------------
# The code below assumes that we are only dealing with default
# organic molecules whose atoms have single letter element symbols.
# ------------------------- IMPORTANT -------------------------
for _neighbor, hydrogens in _neighbors_H_dict.items():
if len(hydrogens) == 1:
if _neighbor.element == "C":
_n = _neighbor.id[1:]
else:
_n = _neighbor.id
hydrogens[0].id = f"H{_n}"
else:
for i, hydrogen in enumerate(hydrogens):
if _neighbor.element == "C":
_n = _neighbor.id[1:]
else:
_n = _neighbor.id
hydrogen.id = f"H{_n}{i+1}"
return molecule
[docs]
def change_bond_order(molecule, atom1, atom2, order):
"""
Change the bond order between two atoms. This will also adjust the protonation state and add or remove hydrogens if necessary.
This function will not, however, adjust the overall geometry of the molecule. It can currently only adjust the local geometry of the atoms involved and their hydrogen partners.
Parameters
----------
molecule : Molecule
The molecule to change the bond order in.
atom1 : Atom
The first atom of the bond.
atom2 : Atom
The second atom of the bond.
order : int
The new bond order. This can be either 1, 2, or 3.
"""
# check if the bond order is valid
if order not in (1, 2, 3):
raise ValueError(f"Invalid bond order {order}.")
bond = molecule.get_bond(atom1, atom2)
if bond is None:
raise ValueError(f"No bond found between {atom1} and {atom2}.")
# check if the bond order is the same
if bond.order == order:
return
# now remove all hydrogens from the atoms
hydrogens = []
for atom in (atom1, atom2):
for hydrogen in molecule.get_neighbors(atom):
if hydrogen.element == "H":
hydrogens.append(hydrogen)
molecule.remove_atoms(*hydrogens)
# set the new bond order
bond.order = order
# adjust the bond length
length = bond_length_by_order[order][atom1.element][atom2.element]
base.adjust_bond_length(bond, length)
# now add the hydrogens back
H = Hydrogenator()
H.add_hydrogens(atom1, molecule)
H.add_hydrogens(atom2, molecule)
return molecule
[docs]
def find_equatorial_substituents(molecule):
"""
Find all atoms in a molecule that are equatorial to some ring within the molecule.
Parameters
----------
molecule : Molecule
The molecule to search in
Returns
-------
list
A list of atoms that are equatorial to some ring.
"""
rings = molecule._AtomGraph.find_cycles()
equatorial_atoms = []
for ring in rings:
ring_mean = np.mean([atom.get_coord() for atom in ring], axis=0)
ring_mean = np.array(ring_mean)
for atom in ring:
neighbors = molecule.get_neighbors(atom)
if len(neighbors) < 3:
continue
neighbors = list(neighbors)
vec = atom.get_coord() - ring_mean
for neighbor in neighbors:
if neighbor in ring:
continue
neighbor_vec = neighbor.get_coord() - atom.get_coord()
angle = np.arccos(
np.dot(vec, neighbor_vec)
/ (np.linalg.norm(vec) * np.linalg.norm(neighbor_vec))
)
angle = np.degrees(angle)
if angle < 45:
equatorial_atoms.append(neighbor)
break
return equatorial_atoms
[docs]
def find_axial_substituents(molecule):
"""
Find all atoms in a molecule that are axial to some ring within the molecule.
Parameters
----------
molecule : Molecule
The molecule to search in
Returns
-------
list
A list of atoms that are axial to some ring.
"""
rings = molecule._AtomGraph.find_cycles()
axial_atoms = []
for ring in rings:
ring_mean = np.mean([atom.get_coord() for atom in ring], axis=0)
ring_mean = np.array(ring_mean)
for atom in ring:
neighbors = molecule.get_neighbors(atom)
if len(neighbors) < 3:
continue
neighbors = list(neighbors)
vec = atom.get_coord() - ring_mean
for neighbor in neighbors:
if neighbor in ring:
continue
neighbor_vec = neighbor.get_coord() - atom.get_coord()
angle = np.arccos(
np.dot(vec, neighbor_vec)
/ (np.linalg.norm(vec) * np.linalg.norm(neighbor_vec))
)
angle = np.degrees(angle)
if angle > 55:
axial_atoms.append(neighbor)
break
return axial_atoms
[docs]
def find_equatorial_hydrogens(molecule):
"""
Find the equatorial hydrogen atoms in a molecule.
Parameters
----------
molecule : Molecule
The molecule to search in
Returns
-------
list
The equatorial hydrogen atoms.
"""
rings = molecule._AtomGraph.find_cycles()
equatorial_Hs = []
# v = molecule.draw()
for ring in rings:
ring_mean = np.mean([atom.get_coord() for atom in ring], axis=0)
ring_mean = np.array(ring_mean)
for atom in ring:
neighbors = molecule.get_neighbors(atom)
if len(neighbors) < 3:
continue
neighbors = list(neighbors)
vec = atom.get_coord() - ring_mean
Hs = [i for i in neighbors if i.element == "H"]
if len(Hs) < 1:
continue
for H in Hs:
H_vec = H.get_coord() - atom.get_coord()
angle = np.arccos(
np.dot(vec, H_vec) / (np.linalg.norm(vec) * np.linalg.norm(H_vec))
)
angle = np.degrees(angle)
if angle < 45:
equatorial_Hs.append(H)
break
# v.draw_atoms(*equatorial_Hs, colors="red")
# v.show()
return equatorial_Hs
[docs]
def find_axial_hydrogens(molecule):
"""
Find the axial hydrogen atoms in a molecule.
Parameters
----------
molecule : Molecule
The molecule to search in
Returns
-------
list
The axial hydrogen atoms.
"""
rings = molecule._AtomGraph.find_cycles()
axial_Hs = []
# v = molecule.draw()
for ring in rings:
ring_mean = np.mean([atom.get_coord() for atom in ring], axis=0)
ring_mean = np.array(ring_mean)
for atom in ring:
neighbors = molecule.get_neighbors(atom)
if len(neighbors) < 3:
continue
neighbors = list(neighbors)
vec = atom.get_coord() - ring_mean
Hs = [i for i in neighbors if i.element == "H"]
if len(Hs) < 1:
continue
for H in Hs:
H_vec = H.get_coord() - atom.get_coord()
angle = np.arccos(
np.dot(vec, H_vec) / (np.linalg.norm(vec) * np.linalg.norm(H_vec))
)
angle = np.degrees(angle)
if angle > 55:
axial_Hs.append(H)
break
# v.draw_atoms(*axial_Hs, colors="red")
# v.show()
return axial_Hs
[docs]
def get_equatorial_hydrogen_neighbor(molecule, atom):
"""
Get the equatorial hydrogen atom of a given atom.
Parameters
----------
molecule : Molecule
The molecule to search in
atom : Atom
The atom to search for
Returns
-------
Atom
The equatorial hydrogen atom (if present, or None if not present)
"""
ring = next((i for i in molecule._AtomGraph.find_cycles() if atom in i), None)
if ring is None:
return None
ring_mean = np.mean([atom.get_coord() for atom in ring], axis=0)
ring_mean = np.array(ring_mean)
neighbors = molecule.get_neighbors(atom)
if len(neighbors) < 3:
return None
neighbors = list(neighbors)
vec = atom.get_coord() - ring_mean
Hs = [i for i in neighbors if i.element == "H"]
if len(Hs) < 1:
return None
for H in Hs:
H_vec = H.get_coord() - atom.get_coord()
angle = np.arccos(
np.dot(vec, H_vec) / (np.linalg.norm(vec) * np.linalg.norm(H_vec))
)
angle = np.degrees(angle)
if angle < 45:
return H
return None
[docs]
def get_axial_hydrogen_neighbor(molecule, atom):
"""
Get the axial hydrogen atom of a given atom.
Parameters
----------
molecule : Molecule
The molecule to search in
atom : Atom
The atom to search for
Returns
-------
Atom
The axial hydrogen atom (if present, or None if not present)
"""
ring = next((i for i in molecule._AtomGraph.find_cycles() if atom in i), None)
if ring is None:
return None
ring_mean = np.mean([atom.get_coord() for atom in ring], axis=0)
ring_mean = np.array(ring_mean)
neighbors = molecule.get_neighbors(atom)
if len(neighbors) < 3:
return None
neighbors = list(neighbors)
vec = atom.get_coord() - ring_mean
Hs = [i for i in neighbors if i.element == "H"]
if len(Hs) < 1:
return None
for H in Hs:
H_vec = H.get_coord() - atom.get_coord()
angle = np.arccos(
np.dot(vec, H_vec) / (np.linalg.norm(vec) * np.linalg.norm(H_vec))
)
angle = np.degrees(angle)
if angle > 55:
return H
return None
[docs]
def get_equatorial_neighbor(molecule, atom):
"""
Get the equatorial atom of a given atom.
Parameters
----------
molecule : Molecule
The molecule to search in
atom : Atom
The atom to search for
Returns
-------
Atom
The equatorial atom (if present, or None if not present)
"""
ring = next((i for i in molecule._AtomGraph.find_cycles() if atom in i), None)
if ring is None:
return None
ring_mean = np.mean([atom.get_coord() for atom in ring], axis=0)
ring_mean = np.array(ring_mean)
neighbors = molecule.get_neighbors(atom)
if len(neighbors) < 3:
return None
neighbors = list(neighbors)
vec = atom.get_coord() - ring_mean
for neighbor in neighbors:
if neighbor in ring:
continue
neighbor_vec = neighbor.get_coord() - atom.get_coord()
angle = np.arccos(
np.dot(vec, neighbor_vec)
/ (np.linalg.norm(vec) * np.linalg.norm(neighbor_vec))
)
angle = np.degrees(angle)
if angle < 45:
return neighbor
return None
[docs]
def get_axial_neighbor(molecule, atom):
"""
Get the axial atom of a given atom.
Parameters
----------
molecule : Molecule
The molecule to search in
atom : Atom
The atom to search for
Returns
-------
Atom
The axial atom (if present, or None if not present)
"""
ring = next((i for i in molecule._AtomGraph.find_cycles() if atom in i), None)
if ring is None:
return None
ring_mean = np.mean([atom.get_coord() for atom in ring], axis=0)
ring_mean = np.array(ring_mean)
neighbors = molecule.get_neighbors(atom)
if len(neighbors) < 3:
return None
neighbors = list(neighbors)
vec = atom.get_coord() - ring_mean
for neighbor in neighbors:
if neighbor in ring:
continue
neighbor_vec = neighbor.get_coord() - atom.get_coord()
angle = np.arccos(
np.dot(vec, neighbor_vec)
/ (np.linalg.norm(vec) * np.linalg.norm(neighbor_vec))
)
angle = np.degrees(angle)
if angle > 55:
return neighbor
return None
[docs]
def get_left_hydrogen_neighbor(molecule, atom):
"""
Get the "left-protruding" hydrogen neighbor of an atom
that has two hydrogen neighbors.
Parameters
----------
molecule : Molecule
The molecule to search in
atom : Atom
The atom to search for
Returns
-------
Atom
The left hydrogen atom.
If the nomenclature does not apply to the atom (e.g. because it is completely symmetrical on both sides) any of the two hydrogen atoms is returned.
If the atom does not have two hydrogen neighbors, None may be returned if the only hydrogen neighbor is not in the correct orientation, otherwise the hydrogen neighbor is returned.
Example
-------
In a molecule:
```
H_B
|
CH3 -- C -- CH2 -- OH
|
H_A
```
We want to get the left and right hydrogens of the central C atom (labeled only C).
Using part of the logic behind R/S nomenclature for chiral centers, we prioritize the non-H neighbors
and then rotate the molecule such that the highest order non-H neighbor points toward the user and the other
non-H neighbor points away. The left and right hydrogens are then determined based on their orientation in this view.
In this case, the left hydrogen is H_A and the right hydrogen is H_B.
"""
Hs, vec, H_vecs = _core_left_right_hydrogens(molecule, atom)
# get the cross product of the two vectors
cross = np.cross(vec, H_vecs[0])
# if the cross product is pointing in the same direction as the second hydrogen, return the first hydrogen
if np.dot(cross, H_vecs[1]) > 0:
return Hs[0]
return Hs[1]
[docs]
def split_into_contiguous_residues(molecule, target_residues: list = None):
"""
In case a molecule contains residues that include multiple contiguous atom groups,
split these into multiple residues. Note that the residues that are split will be removed from the molecule!
Parameters
----------
molecule : Molecule
The molecule to split into contiguous residues.
target_residues : list
A list of residues to split. If None, all residues will be split.
"""
if not molecule.count_bonds():
raise ValueError(
"The molecule has no bonds. Cannot split into contiguous residues due to missing connectivity information. First add bonds, for example by running `molecule.infer_bonds()`."
)
atom_graph = molecule.get_atom_graph()
if target_residues is not None:
target_residues = molecule.get_residues(target_residues)
other_residues = [
res for res in molecule.get_residues() if res not in target_residues
]
atom_nodes_to_drop = set()
for res in other_residues:
atom_nodes_to_drop.update(res.child_list)
atom_graph.remove_nodes_from(atom_nodes_to_drop)
contiguous_subgraphs = nx.connected_components(atom_graph)
old_residues_to_remove = set()
for i, subgraph in enumerate(contiguous_subgraphs):
new_residue = base_classes.Residue(resname=f"UNL_{i+1}")
molecule.add_residues(new_residue)
for atom in subgraph:
current_residue = atom.parent
current_residue.detach_child(atom.get_id())
new_residue.add(atom)
old_residues_to_remove.add(current_residue)
molecule.remove_residues(old_residues_to_remove)
return molecule
[docs]
def get_right_hydrogen_neighbor(molecule, atom):
"""
Get the "right-protruding" hydrogen neighbor of an atom
that has two hydrogen neighbors.
Parameters
----------
molecule : Molecule
The molecule to search in
atom : Atom
The atom to search for
Returns
-------
Atom
The right hydrogen atom.
If the nomenclature does not apply to the atom (e.g. because it is completely symmetrical on both sides) any of the two hydrogen atoms is returned.
If the atom does not have two hydrogen neighbors, None may be returned if the only hydrogen neighbor is not in the correct orientation, otherwise the hydrogen neighbor is returned.
Example
-------
In a molecule:
```
H_B
|
CH3 -- C -- CH2 -- OH
|
H_A
```
We want to get the left and right hydrogens of the central C atom (labeled only C).
Using part of the logic behind R/S nomenclature for chiral centers, we prioritize the non-H neighbors
and then rotate the molecule such that the highest order non-H neighbor points toward the user and the other
non-H neighbor points away. The left and right hydrogens are then determined based on their orientation in this view.
In this case, the left hydrogen is H_A and the right hydrogen is H_B.
"""
Hs, vec, H_vecs = _core_left_right_hydrogens(molecule, atom)
# get the cross product of the two vectors
cross = np.cross(vec, H_vecs[0])
# if the cross product is pointing in the same direction as the second hydrogen, return the second hydrogen
if np.dot(cross, H_vecs[1]) > 0:
return Hs[1]
return Hs[0]
def _core_left_right_hydrogens(molecule, atom):
"""The base function for finding left/right hydrogens"""
neighbors = molecule.get_neighbors(atom)
Hs = [i for i in neighbors if i.element == "H"]
if len(Hs) != 2:
return None
non_Hs = [i for i in neighbors if i.element != "H"]
if len(non_Hs) != 2:
Hs = (Hs[0], None)
# sort the non-H neighbors
a_num_A = atomic_number(non_Hs[0].element)
a_num_B = atomic_number(non_Hs[1].element)
if a_num_A > a_num_B:
non_Hs = (non_Hs[0], non_Hs[1])
elif a_num_A < a_num_B:
non_Hs = (non_Hs[1], non_Hs[0])
else:
non_Hs = sorted(non_Hs, key=lambda x: _neighbor_sort_key(molecule, x))
# get the vector between the two non-H neighbors
vec = non_Hs[0].get_coord() - non_Hs[1].get_coord()
# get the vector between the central atom and the two hydrogens
H_vecs = [i.get_coord() - atom.get_coord() for i in Hs]
return Hs, vec, H_vecs
def _neighbor_sort_key(molecule, atom):
neighbors = molecule.get_neighbors(atom)
key = sum(
atomic_number(i.element) * molecule.get_bond(atom, i).order ** 2
for i in neighbors
)
return key
[docs]
def vet_structure(
molecule, clash_range: tuple = (0.6, 2.7), angle_range: tuple = (90, 180)
) -> bool:
"""
Check for basic structure integrity.
This will return False if there are clashes within the structure,
or invalid angles.
Parameters
----------
molecule : Molecule
A BuildAMol Molecule
clash_range : tuple
The minimal and maximal allowed distances between bonded atoms (in Angstrom).
The lower limit is also used for non-bonded atoms.
angle_range : tuple
The minimal and maximal allowed angle between a triplet of adjacent bonded atoms (in degrees).
Returns
-------
bool
True if the structure is free from any obstacles,
False otherwise.
"""
for a, b in molecule.get_bonds():
d = base.compute_distance(a, b)
if not clash_range[0] <= d <= clash_range[1]:
return False
for angle in molecule.compute_angles().values():
if not angle_range[0] <= angle <= angle_range[1]:
return False
for a in molecule.get_atoms():
for b in molecule.get_atoms():
if a is b:
continue
dist = base.compute_distance(a, b)
if dist <= clash_range[0]:
return False
return True
[docs]
def find_clashes(molecule, min_dist: float = 1.0, ignore_hydrogens: bool = False):
"""
Find all clashing atoms in a molecule.
Parameters
----------
molecule : Molecule
The molecule to check for clashes.
min_dist : float
The minimal allowed distance between atoms (in Angstrom).
ignore_hydrogens : bool
If set to True, hydrogen atoms are ignored.
Yields
------
tuple
A tuple of clashing atoms.
"""
warnings.deprecation.warn(
"find_clashes is deprecated and will be removed in a future version. Use find_clashes_between instead.",
DeprecationWarning,
)
yield from find_clashes_between(
molecule, molecule, min_dist, ignore_hydrogens, False
)
[docs]
def find_clashes_between(
mol_a,
mol_b,
min_dist: float = 1.0,
ignore_hydrogens: bool = False,
coarse_precheck: bool = True,
):
"""
Find all clashing atoms between two sets of atoms.
Parameters
----------
mol_a, mol_b : Molecule
Two molecules to check for clashes.
min_dist : float
The minimal allowed distance between atoms (in Angstrom).
ignore_hydrogens : bool
If set to True, hydrogen atoms are ignored.
coarse_precheck : bool
If set to True, a coarse-grain precheck is performed on residue-level before checking for clashes on atom-level.
This will speed up the process for large molecules but may miss clashes if individual residues are particularly large (e.g. lipids with long tails).
Yields
------
tuple
A tuple of clashing atoms.
"""
# first make a rough distance matrix on residue-level
residues_a = list(mol_a.get_residues())
residues_b = list(mol_b.get_residues())
r_a = np.empty((len(residues_a)), dtype=object)
r_b = np.empty((len(residues_b)), dtype=object)
r_a[:] = residues_a
r_b[:] = residues_b
residues_a = r_a
residues_b = r_b
if coarse_precheck and len(residues_a) > 1 and len(residues_b) > 1:
residue_coords_a = np.array([r.center_of_mass() for r in residues_a])
residue_coords_b = np.array([r.center_of_mass() for r in residues_b])
residue_dists = cdist(residue_coords_a, residue_coords_b)
np.fill_diagonal(residue_dists, np.inf)
residue_edge_mask = np.zeros(residue_dists.shape, dtype=bool)
for i in range(len(residues_a)):
for j in range(len(residues_b)):
if residue_dists[i, j] < 12:
residue_edge_mask[i, j] = True
else:
residue_edge_mask = np.ones((len(residues_a), len(residues_b)), dtype=bool)
for i in range(len(residues_a)):
residue_a = residues_a[i]
close_by_residues = residues_b[residue_edge_mask[i]]
if ignore_hydrogens:
atoms_a = [a for a in residue_a.get_atoms() if a.element != "H"]
atoms_b = []
for residue_b in close_by_residues:
atoms_b.extend([a for a in residue_b.get_atoms() if a.element != "H"])
else:
atoms_a = list(residue_a.get_atoms())
atoms_b = []
for residue_b in close_by_residues:
atoms_b.extend(residue_b.get_atoms())
atoms_a = np.array(atoms_a, dtype=object)
atoms_b = np.array(atoms_b, dtype=object)
coords_a = np.array([a.get_coord() for a in atoms_a])
coords_b = np.array([a.get_coord() for a in atoms_b])
dists = cdist(coords_a, coords_b)
np.fill_diagonal(dists, np.inf)
xs, ys = np.where((0 < dists) * (dists < min_dist))
for x, y in zip(xs, ys):
yield atoms_a[x], atoms_b[y]
[docs]
def sample_atoms_around_reference(
reference_coord: np.ndarray,
candidates: np.ndarray,
num_samples: int,
max_radius: float = 10.0,
):
"""
Sample atoms around a reference coordinate. Such that they are spacially evenly distributed around the central reference coordinates.
Parameters
----------
reference_coord : np.ndarray
The reference coordinate to sample around.
candidates : np.ndarray
The atoms to sample from. This must be an array of Atom objects.
num_samples : int
The number of samples to generate.
max_radius : float
The maximum radius to sample for.
Returns
-------
samples : np.ndarray
The sampled atoms.
"""
# Get the coordinates of the atoms
coordinates = np.array([i.coord for i in candidates])
# Generate azimuth and elevation angles evenly spaced in a sphere
phi = np.linspace(0, 2 * np.pi, num_samples)
theta = np.linspace(0, np.pi, num_samples)
# Create a grid of angles
phi_grid, theta_grid = np.meshgrid(phi, theta)
# Convert spherical coordinates to Cartesian coordinates
x = max_radius * np.sin(theta_grid) * np.cos(phi_grid) + reference_coord[0]
y = max_radius * np.sin(theta_grid) * np.sin(phi_grid) + reference_coord[1]
z = max_radius * np.cos(theta_grid) + reference_coord[2]
# Combine the x, y, z coordinates to get the sampled points
sampled_coordinates = np.column_stack((x.ravel(), y.ravel(), z.ravel()))
# Find the closest coordinates from the possible_coordinates array
closest_indices = np.argmin(
np.linalg.norm(sampled_coordinates[:, None] - coordinates, axis=2),
axis=1,
)
samples = candidates[closest_indices]
return samples
[docs]
def compute_residue_radius(residue):
"""
Compute the radius of a residue by computing the distance between its center of mass
and the furthest atom.
Parameters
----------
residue : Bio.PDB.Residue.Residue
The residue to compute the radius for.
Returns
-------
radius : float
The radius of the residue.
"""
atoms = list(residue.get_atoms())
atom_coords = np.array([atom.get_coord() for atom in atoms])
center = residue.center_of_mass()
distances = np.linalg.norm(atom_coords - center, axis=1)
radius = np.max(distances)
return radius
[docs]
def compute_outlier_atoms(residue, f: float = 1.5):
"""
Compute which atoms of a residue are especially far away from the residues center of mass.
This function compute the distances between the center of mass of the residue and its atoms
and returns all atoms are further than `f * p75` away from the center of mass, where `p75`
is the 75th percentile of the distances.
Parameters
----------
residue : Bio.PDB.Residue.Residue
The residue to compute the outlier atoms for.
f : float
The factor to multiply the 75th percentile with.
Returns
-------
outlier_atoms : list
A list of atoms that are considered outliers.
"""
atoms = list(residue.get_atoms())
atom_coords = np.array([atom.get_coord() for atom in atoms])
center = residue.center_of_mass()
distances = np.linalg.norm(atom_coords - center, axis=1)
p75 = np.percentile(distances, 75)
f = f * p75
outlier_atoms = [atom for atom, distance in zip(atoms, distances) if distance > f]
return outlier_atoms
[docs]
def infer_surface_residues(
structure,
cutoff: int = 75,
fraction: float = None,
):
"""
Infer residues that are likely to be on the surface of the structure
using the Solvent accessible surface area (SASA) of the structure.
Parameters
----------
structure : Bio.PDB.Structure.Structure
The structure to infer the surface residues from.
n_points : int
The number of points to sample on the surface of the structure.
cutoff : int
The cutoff to use for classifying residues as surface residues.
fraction : float
The fraction of residues to classify as surface residues. In this case,
the cutoff is adjusted to match the fraction of residues.
Returns
-------
surface_residues : list
A list of residues that are likely to be on the surface of the structure.
"""
sasa = defaults.get_default_instance("bioSASA")
sasa.compute(structure, level="R")
sasa_values = np.array([residue.sasa for residue in structure.get_residues()])
sasa_values = sasa_values / sasa_values.max() * 100
if fraction is not None:
cutoff = np.percentile(sasa_values, 100 - fraction * 100)
surface_residues = [
residue
for residue, sasa in zip(structure.get_residues(), sasa_values)
if sasa > cutoff
]
return surface_residues
[docs]
def infer_residue_connections(
structure,
bond_length: float = None,
triplet: bool = False,
):
"""
Infer the connectivity graph of residues from the distances between atoms of residue pairs.
This will establish only bonds between close-by atoms from non-identical residues.
Parameters
----------
structure : Bio.PDB.Structure.Structure
The structure to infer the bonds from. This can be any of the following objects which host at least two Residues:
- `Bio.PDB.Structure`
- `Bio.PDB.Model`
- `Bio.PDB.Chain`
bond_length : float
The maximum distance between two atoms to be considered a bond.
triplet : bool
If True, bonds between atoms of the same residue are also added, if one
of the atoms is considered bonded to another residue. Like this residue connections
are described not by a single bond with a pair of atoms, but two bonds with a triplet of atoms.
Returns
-------
bonds : list
A list of tuples of Atoms from different Residues that are bonded.
"""
if not triplet:
if bond_length is None:
bond_length = defaults.DEFAULT_BOND_LENGTH / 2, defaults.DEFAULT_BOND_LENGTH
elif isinstance(bond_length, (int, float)):
bond_length = defaults.DEFAULT_BOND_LENGTH / 2, bond_length
min_length, max_length = bond_length
bonds = []
_seen_residues = set()
for residue1 in structure.get_residues():
for residue2 in structure.get_residues():
if residue1 == residue2:
continue
elif residue2 in _seen_residues:
continue
atoms = list(i for i in residue1.get_atoms() if i.element != "H")
atoms.extend(i for i in residue2.get_atoms() if i.element != "H")
_neighbors = NeighborSearch(atoms)
_neighbors = _neighbors.search_all(radius=max_length)
_neighbors = (
i
for i in _neighbors
if (i[0].element != "H" and i[1].element != "H")
and i[0].get_parent() != i[1].get_parent()
and np.linalg.norm(i[0].coord - i[1].coord) > min_length
)
bonds.extend(_neighbors)
_seen_residues.add(residue1)
else:
connections = infer_residue_connections(
structure, bond_length=bond_length, triplet=False
)
base_bonds = infer_bonds(
structure, bond_length=bond_length, restrict_residues=True
)
_additional_bonds = []
for atom1, atom2 in connections:
_new = (bond for bond in base_bonds if atom1 in bond)
_additional_bonds.extend(_new)
bonds = connections + _additional_bonds
return bonds
[docs]
def infer_bonds(structure, bond_length: float = None, restrict_residues: bool = True):
"""
Generate a connectivity graph by inferring bonds from the distance between atoms.
Parameters
----------
structure : Bio.PDB.Structure.Structure
The structure to infer the bonds from. This can be any of the following objects which host Residues:
- `Bio.PDB.Structure`
- `Bio.PDB.Model`
- `Bio.PDB.Chain`
- `Bio.PDB.Residue`
bond_length : float or tuple
The maximum distance between two atoms to be considered a bond.
If a tuple is provided, it specifies the minimal and maximal distances between atoms.
restrict_residues : bool
If set to `True`, only bonds between atoms of the same residue will be considered.
Returns
-------
bonds : list
The connectivity graph of the molecule, storing tuples of `Bio.PDB.Atom` objects.
"""
if bond_length is None:
bond_length = (defaults.DEFAULT_BOND_LENGTH / 2, defaults.DEFAULT_BOND_LENGTH)
elif isinstance(bond_length, (int, float)):
bond_length = (defaults.DEFAULT_BOND_LENGTH / 2, bond_length)
min_length, max_length = bond_length
if restrict_residues:
bonds = []
for residue in structure.get_residues():
atoms = list(residue.get_atoms())
_neighbors = NeighborSearch(atoms)
bonds.extend(
_neighbors.search_all(radius=max_length),
)
else:
atoms = list(structure.get_atoms())
_neighbors = NeighborSearch(atoms)
bonds = _neighbors.search_all(radius=max_length)
bonds = [
i
for i in bonds
if not (i[0].element == "H" and i[1].element == "H")
and np.linalg.norm(i[0].coord - i[1].coord) > min_length
]
bonds = _prune_H_triplets(bonds)
return bonds
[docs]
def infer_bond_orders(molecule):
"""
Infer the bond orders using the registered higher order functional groups (i.e. functional groups with bonds of order > 1).
Parameters
----------
molecule : Molecule
The molecule to infer the bond orders for.
"""
import buildamol.structural.groups as groups
group_matches = {}
_assigned_atoms = set()
groups_to_apply = sorted(
groups.higher_order_groups, key=lambda x: x.rank, reverse=True
)
for atom in molecule.get_atoms():
neighbors = molecule.get_neighbors(atom)
atoms = (atom, *neighbors)
for group in groups_to_apply:
if atoms in group_matches:
continue
if all(i in _assigned_atoms for i in atoms):
continue
if group.matches(molecule, atoms):
if any(
i in _assigned_atoms
for i in group._assignment_cache[molecule][-1].values()
):
continue
group_matches[atoms] = (
group,
group._assignment_cache[molecule][-1],
)
_assigned_atoms.update(group._assignment_cache[molecule][-1].values())
for atoms, (group, assignment) in group_matches.items():
group._assignment = assignment
group.apply_connectivity(molecule, atoms)
def _atom_from_residue(id, residue):
return next((atom for atom in residue.get_atoms() if atom.id == id), None)
[docs]
def has_free_valence(atom, bonds, needed: int = 1):
"""
Check if an atom has free valence.
Parameters
----------
atom : Atom
The atom to check for free valence.
bonds : list
A list of Bond objects that connect the atom to other atoms.
needed : int
The number of free valences needed.
Returns
-------
bool
True if the atom has free valence, False otherwise.
"""
degree = sum(bond.order for bond in bonds)
return degree <= element_connectivity.get(atom.element, 0) - needed
[docs]
def change_element(atom, new_element: str, _molecule):
"""
Change the element of an atom and update its connectivity accordingly.
This will remove hydrogen atoms if the new element has a lower connectivity,
or add them.
"""
old_element = atom.element
atom.set_element(new_element, adjust_id=False)
atom.set_charge(0)
new_connectivity = element_connectivity.get(new_element, 0)
# reference_connectivity = element_connectivity.get(old_element, 0)
if _molecule.get_degree(atom) > new_connectivity:
neighbors = _molecule.get_neighbors(atom)
to_remove = []
loops = 0
while _molecule.get_degree(atom) > new_connectivity:
for neighbor in neighbors:
if neighbor.element == "H":
to_remove.append(neighbor)
neighbors.remove(neighbor)
new_connectivity += 1
break
loops += 1
if loops > 100:
leftover_charge = _molecule.get_degree(atom) - new_connectivity
if leftover_charge > acceptable_surplus_charge:
raise ValueError(
f"Could not change element of atom {atom} to {new_element}. Not enough hydrogen atoms available to remove, and without hydrogens the atom would have a charge of {leftover_charge}! Maybe check your input or manually use `atom.set_element` to override the element."
)
else:
atom.set_charge(leftover_charge)
break
_molecule.remove_atoms(*to_remove)
elif _molecule.get_degree(atom) < new_connectivity:
hydrogenator = Hydrogenator()
hydrogenator.add_hydrogens(atom, _molecule)
# I haven't come up with an example where this is needed, actually
# but it's here just in case
if _molecule.get_degree(atom) < new_connectivity:
leftover_charge = new_connectivity - _molecule.get_degree(atom)
if abs(leftover_charge) > acceptable_surplus_charge:
raise ValueError(
f"Could not change element of atom {atom} to {new_element}. Not enough hydrogen atoms available to add, and without hydrogens the atom would have a charge of {leftover_charge}! Maybe check your input or manually use `atom.set_element` to override the element."
)
else:
atom.set_charge(leftover_charge)
# def aromatic_to_double(bonds: list) -> list:
# """
# Set bonds between aromatic atoms to single and double bonds
# This is used to convert aromatic bonds from RDKit which have a bond order of 1.5 to a double bond.
# Parameters
# ----------
# bonds : list
# A list of Bond objects.
# Yields
# -------
# int
# The bond order of the bond.
# """
# connectivity = defaultdict(int)
# for bond in bonds:
# atom1, atom2 = bond
# connectivity[atom1] += bond.order
# connectivity[atom2] += bond.order
# for bond in bonds:
# atom1, atom2 = bond
# n_bonds_1 = connectivity[atom1]
# n_bonds_2 = connectivity[atom2]
# # aromatic carbons can have 3 or 4 bonds
# # with 3 bonds they still have room left for one more bond
# # with 4 bonds they are fully saturated
# if atom1.element == "C" and atom2.element == "C":
# if bond.order == int(bond.order):
# yield int(bond.order)
# continue
# if n_bonds_1 == 3 or n_bonds_2 == 3:
# connectivity[atom1] += 1
# connectivity[atom2] += 1
# yield 2 # double bond
# continue
# elif n_bonds_1 == 4 or n_bonds_2 == 4:
# connectivity[atom1] -= 1
# connectivity[atom2] -= 1
# yield 1
# continue
# # aromatic bonds from RDKit have 1.5 bond order
# elif bond.order == 1.5:
# yield 1 # single bond
# continue
# # yield any other bond orders as they are
# if bond.order != int(bond.order):
# yield bond.order
# else:
# yield int(bond.order)
[docs]
def apply_reference_bonds(structure, _compounds=None):
"""
Apply bonds according to loaded reference compounds. This will compute a list of tuples with bonded
atoms from the same residue. It will not infer residue-residue connections! It is possible to provide a single
atom as input structure, in which case all bonds that involve said atom are returned.
Parameters
----------
structure
The structure to apply the bonds to. This can be any of the following objects which hosts Atoms:
- `buildamol.Structure`
- `buildamol.Model`
- `buildamol.Chain`
- `buildamol.Residue`
_compounds : PDBECompounds
The reference compounds to use for bond inference. If not provided, the default compounds are used.
Returns
-------
bonds : list
A list of tuples of Atoms that are bonded.
"""
if _compounds is None:
_compounds = resources.get_default_compounds()
if structure.level == "R":
residue = structure
if not _compounds.has_residue(residue.resname):
warnings.warn(
f"[ignoring] No reference residue found in Compounds for {residue.resname}!"
)
return []
ref = _compounds.get(residue.resname)
bonds = (
(
_atom_from_residue(bond.atom1.id, residue),
_atom_from_residue(bond.atom2.id, residue),
bond.order,
)
for bond in ref.get_bonds()
)
bonds = [
bond for bond in bonds if bond[1] is not None and bond[0] is not None
] # make sure to have no None entries...
return bonds
elif structure.level == "A":
residue = structure.get_parent()
bonds = apply_reference_bonds(residue, _compounds)
bonds = [
bond
for bond in bonds
if bond[0].id == structure.id or bond[1].id == structure.id
]
return bonds
else:
bonds = []
for residue in structure.get_residues():
bonds.extend(apply_reference_bonds(residue, _compounds))
return bonds
[docs]
def atoms_in_area(structure, center, radius):
"""
Get all atoms in a given area around a center point.
Parameters
----------
structure : Structure
The structure to search for atoms.
center : np.ndarray
The center point of the area to search.
radius : float
The radius of the area to search.
Yields
------
Atom
The atoms in the area.
"""
for atom in structure.get_atoms():
if np.linalg.norm(atom.coord - center) < radius:
yield atom
[docs]
def compute_internal_coordinates(bonds: list):
"""
Compute internal coordinates for a structure.
Parameters
----------
bonds : list
A list of tuples of atoms that are bonded.
The atoms must be `Bio.PDB.Atom` objects with coordinates.
Returns
-------
list
A list of InternalCoordinates
"""
quartets = neighbors.compute_quartets(bonds)
ics = []
for quartet in quartets:
angle_123 = base.compute_angle(quartet[0], quartet[1], quartet[2])
angle_234 = base.compute_angle(quartet[1], quartet[2], quartet[3])
dihedral = base.compute_dihedral(quartet[0], quartet[1], quartet[2], quartet[3])
l_12 = base.compute_distance(quartet[0], quartet[1])
l_13 = base.compute_distance(quartet[0], quartet[2])
l_34 = base.compute_distance(quartet[2], quartet[3])
ic = _ic.InternalCoordinates(
quartet[0].id,
quartet[1].id,
quartet[2].id,
quartet[3].id,
l_12,
l_34,
angle_123,
angle_234,
dihedral,
l_13 if quartet.improper else None,
improper=quartet.improper,
)
ics.append(ic)
return ics
[docs]
def compute_atom1_from_others(coords2, coords3, coords4, ic):
"""
Compute the coordinates of the first atom from internal coordinates and the coordinates of the other three.
Parameters
----------
*coords: array-like
The coordinates of the other three atoms
ic : InternalCoordinates
The internal coordinates
Returns
-------
coords1 : array-like
The coordinates of the first atom
"""
if ic.is_proper:
return base._IC_to_xyz(
coords4,
coords3,
coords2,
anchor=coords2,
r=-ic.bond_length_12,
theta=-np.radians(ic.bond_angle_123),
dihedral=np.radians(ic.dihedral),
)
else:
_vec = base._IC_to_xyz(
coords4,
coords3,
coords2,
anchor=np.full(3, 0),
r=1,
theta=np.radians(ic.bond_angle_234),
dihedral=np.radians(ic.dihedral),
)
if ic.bond_length_13:
_vec *= ic.bond_length_13
else:
BC = np.linalg.norm(coords2 - coords3)
AC = ic.bond_length_12
AB = np.sqrt(
BC**2 + AC**2 - 2 * BC * AC * np.cos(np.radians(ic.bond_angle_123))
)
_vec *= AB
final = coords3 + _vec
return final
[docs]
def compute_atom4_from_others(coords1, coords2, coords3, ic):
"""
Compute the coordinates of the fourth atom from internal coordinates and the coordinates of the other three.
Parameters
----------
*coords: array-like
The coordinates of the other three atoms
ic : InternalCoordinates
The internal coordinates
Returns
-------
coords4 : array-like
The coordinates of the fourth atom
"""
if ic.is_proper:
return base._IC_to_xyz(
coords1,
coords2,
coords3,
anchor=coords3,
r=-ic.bond_length_34,
theta=-np.radians(ic.bond_angle_234),
dihedral=np.radians(ic.dihedral),
)
else:
return base._IC_to_xyz(
coords1,
coords2,
coords3,
anchor=coords3,
r=-ic.bond_length_34,
theta=-np.radians(ic.bond_angle_234),
dihedral=np.radians(ic.dihedral),
)
def _prune_H_triplets(bonds):
"""
Remove and erroneous bonds that connect hydrogens to multiple other atoms.
Parameters
----------
bonds : list of tuples
The bonds to prune.
Returns
-------
bonds : list of tuples
The pruned bonds.
"""
bonds_with_H = [
bond for bond in bonds if bond[0].element == "H" or bond[1].element == "H"
]
triplets = neighbors.generate_triplets(bonds_with_H)
bond_mappings = defaultdict(int)
for a, b in bonds_with_H:
bond_mappings[a] += 1
bond_mappings[b] += 1
for triplet in triplets:
if triplet[1].element != "H":
continue
non_H1, H, non_H2 = triplet
e_non_H1 = non_H1.element.title()
e_non_H2 = non_H2.element.title()
if bond_mappings[non_H1] > element_connectivity[e_non_H1]:
if triplet[:2] in bonds:
bonds.remove(triplet[:2])
bond_mappings[non_H1] -= 1
elif bond_mappings[non_H2] > element_connectivity[e_non_H2]:
if triplet[1:] in bonds:
bonds.remove(triplet[1:])
bond_mappings[non_H2] -= 1
elif _H_id_match(H, non_H1):
if triplet[:2] in bonds:
bonds.remove(triplet[:2])
bond_mappings[non_H1] -= 1
elif _H_id_match(H, non_H2):
if triplet[1:] in bonds:
bonds.remove(triplet[1:])
bond_mappings[non_H2] -= 1
elif _H_dist_match(H, non_H1):
if triplet[:2] in bonds:
bonds.remove(triplet[:2])
bond_mappings[non_H1] -= 1
elif _H_dist_match(H, non_H2):
if triplet[1:] in bonds:
bonds.remove(triplet[1:])
bond_mappings[non_H2] -= 1
else:
warnings.warn(f"Could not prune H triplet! ({triplet=})", RuntimeWarning)
return bonds
def _H_dist_match(H, non_H):
"""
Check if the distance between a hydrogen and a non-hydrogen atom may suggest
they are bonded.
Parameters
----------
H : Bio.PDB.Atom
The hydrogen atom.
non_H : Bio.PDB.Atom
The non-hydrogen atom.
Returns
-------
bool
True if the hydrogen may be bonded to the non-hydrogen atom.
"""
d = np.linalg.norm(H.coord - non_H.coord)
if non_H.element == "C":
return 0.94 < d < 1.1
elif non_H.element == "S":
return 1.15 < d < 1.42
elif non_H.element in ("O", "N"):
return 0.94 < d < 1.07
else:
return 0.7 < d < 1.4
def _H_id_match(H, non_H):
"""
Check if the id of a hydrogen may suggest it belongs to a particular non-H atom.
Parameters
----------
H : Bio.PDB.Atom
The hydrogen atom.
non_H : Bio.PDB.Atom
The non-hydrogen atom.
Returns
-------
bool
True if the hydrogen may belong to the non-hydrogen atom.
"""
if (
non_H.element == "C"
and re.match("C\d.*", non_H.id.upper()) is not None
and re.match("H\d.*", H.id.upper()) is None
):
return False
elif non_H.element != "C" and re.match("H\d.*", H.id.upper()) is not None:
return False
return re.search(non_H.id[1:].upper(), H.id[1:].upper()) is not None
if __name__ == "__main__":
import buildamol as bam
bam.load_sugars()
mol = bam.Molecule.from_compound("GLC")
mol.bonds = []
bonds = apply_reference_bonds(mol.structure)
mol._add_bonds(*bonds)
mol.show()
x = find_clashes(mol)
# mol = bam.Molecule.from_pubchem("GlcNAc")
autolabel(mol)
mol.show()
