def five_element_pharmacophore():
radius = puw.quantity(1.0, "angstroms")
ring_1 = PharmacophoricPoint(feat_type="aromatic ring",
center=puw.quantity([1, 0, 0], "angstroms"),
radius=radius,
direction=[0, 0, 1],
atom_indices=None)
ring_2 = PharmacophoricPoint(feat_type="aromatic ring",
center=puw.quantity([0, 1, 2], "angstroms"),
radius=puw.quantity(1.0, "angstroms"))
acceptor = PharmacophoricPoint(feat_type="hb acceptor",
center=puw.quantity([1, 2, 2], "angstroms"),
radius=radius,
direction=[0, 1, 1])
hb_donor = PharmacophoricPoint(feat_type="hb donor",
center=puw.quantity([1, 2, 2], "angstroms"),
radius=radius,
direction=[0, 1, 1])
hydrophobicity = PharmacophoricPoint(
feat_type="hydrophobicity",
center=puw.quantity([-1, 2, 2], "angstroms"),
radius=radius,
)
return StructuredBasedPharmacophore(pharmacophoric_points=[
acceptor, hb_donor, hydrophobicity, ring_1, ring_2
],
is_sorted=True)
def two_element_pharmacophore():
"""Returns a pharmacophore with an aromatic ring and an hb acceptor"""
radius = puw.quantity(1.0, "angstroms")
ring = PharmacophoricPoint(feat_type="aromatic ring",
center=puw.quantity([1, 0, 0], "angstroms"),
radius=radius,
direction=[0, 0, 1],
atom_indices=None)
acceptor = PharmacophoricPoint(feat_type="hb acceptor",
center=puw.quantity([1, 2, 2], "angstroms"),
direction=[0, 1, 1],
radius=radius)
return StructuredBasedPharmacophore(pharmacophoric_points=[ring, acceptor])
def two_point_pharmacophore() -> Pharmacophore:
"""Returns a pharmacophore with two pharmacophoric points."""
hb_donor = PharmacophoricPoint(
feat_type="hb donor",
center=puw.quantity([1,0,1], "angstroms"),
radius=puw.quantity(1.0, "angstroms")
)
hydrophobicity = PharmacophoricPoint(
feat_type="hydrophobicity",
center=puw.quantity([-1, 0, 3], "angstroms"),
radius=puw.quantity(1.0, "angstroms")
)
return Pharmacophore(pharmacophoric_points=[hb_donor, hydrophobicity])
def test_add_point(three_point_pharmacophore):
hydrophobic = PharmacophoricPoint(
feat_type="hydrophobicity",
center=puw.quantity([-1, 0, 2], "angstroms"),
radius=puw.quantity(1.0, "angstroms")
)
positive = PharmacophoricPoint(
feat_type="positive charge",
center=puw.quantity([3, -1, 4], "angstroms"),
radius=puw.quantity(1.0, "angstroms")
)
pharmacophore = copy.deepcopy(three_point_pharmacophore)
pharmacophore.add_point(hydrophobic)
assert pharmacophore.n_pharmacophoric_points == len(pharmacophore)
assert pharmacophore.n_pharmacophoric_points == 4
# Element should be sorted
assert pharmacophore[1].feature_name == "hydrophobicity"
pharmacophore.add_point(positive)
assert pharmacophore.n_pharmacophoric_points == len(pharmacophore)
assert pharmacophore.n_pharmacophoric_points == 5
assert pharmacophore[2].feature_name == "positive charge"
# Test adding a repetead feature type
hb_acceptor = PharmacophoricPoint(
feat_type="hb acceptor",
center=puw.quantity([-1,0,-1], "angstroms"),
radius=puw.quantity(1.0, "angstroms")
)
pharmacophore.add_point(hb_acceptor)
assert pharmacophore.n_pharmacophoric_points == len(pharmacophore)
assert pharmacophore.n_pharmacophoric_points == 6
assert pharmacophore[0].feature_name == "hb acceptor"
assert pharmacophore[1].feature_name == "hb acceptor"
ring = PharmacophoricPoint(
feat_type="aromatic ring",
center=puw.quantity([-5, -1, -3], "angstroms"),
radius=puw.quantity(1.0, "angstroms")
)
pharmacophore.add_point(ring)
assert pharmacophore.n_pharmacophoric_points == len(pharmacophore)
assert pharmacophore.n_pharmacophoric_points == 7
assert pharmacophore[4].feature_name == "aromatic ring"
assert pharmacophore[5].feature_name == "aromatic ring"
assert pharmacophore[6].feature_name == "aromatic ring"
def five_point_pharmacophore(three_point_pharmacophore) -> Pharmacophore:
hydrophobicity = PharmacophoricPoint(
feat_type="hydrophobicity",
center=puw.quantity([-1, 0, 3], "angstroms"),
radius=puw.quantity(1.0, "angstroms")
)
positive = PharmacophoricPoint(
feat_type="positive charge",
center=puw.quantity([3, -1, 4], "angstroms"),
radius=puw.quantity(1.0, "angstroms")
)
pharmacophore = copy.deepcopy(three_point_pharmacophore)
pharmacophore.add_point(hydrophobicity)
pharmacophore.add_point(positive)
return pharmacophore
def three_element_pharmacophore():
radius = puw.quantity(1.0, "angstroms")
ring = PharmacophoricPoint(feat_type="aromatic ring",
center=puw.quantity([1, 0, 0], "angstroms"),
radius=radius,
direction=[0, 0, 1],
atom_indices=None)
acceptor = PharmacophoricPoint(feat_type="hb acceptor",
center=puw.quantity([1, 2, 2], "angstroms"),
radius=radius,
direction=[0, 1, 1])
excluded = PharmacophoricPoint(feat_type="excluded volume",
center=puw.quantity([2, 1, 2], "angstroms"),
radius=radius)
return StructuredBasedPharmacophore(
pharmacophoric_points=[ring, acceptor, excluded])
def get_pharmacophoric_point(ligand: Chem.Mol, feat_name: str,
atom_indices: Sequence, conformer_index: int,
radius: float,
directionality: bool) -> PharmacophoricPoint:
""" Obtain the coordinates and if specified the direction vector and return a pharmacophoric point.
Parameters
----------
ligand : rdkit.Chem.Mol
A ligand
conformer_index : int
The conformer whose coordinates will be used to obtain the pharmacophoric
points.
radius : float
Lenght of the radius in angstroms of the parmacohporic point.
directionality : bool
Whether to compute the direction vectgor of that point.
Returns
-------
openpharmacophore.PharmacophoricPoint
A pharmacophoric point.
"""
if len(atom_indices) > 1:
# Find the centroid
# Aromatic, hydrophobic, positive or negative feature
coords = PharmacophoricPointExtractor._feature_centroid(
ligand, atom_indices, conformer_index)
# Find direction vector
if directionality:
direction = PharmacophoricPointExtractor._aromatic_direction_vector(
ligand, atom_indices, conformer_index)
else:
direction = None
else:
# Find the centroid
# Donor or acceptor feature
position = ligand.GetConformer(conformer_index).GetAtomPosition(
atom_indices[0])
coords = np.zeros((3, ))
coords[0] = position.x
coords[1] = position.y
coords[2] = position.z
# Find direction vector
if directionality:
direction = PharmacophoricPointExtractor._donor_acceptor_direction_vector(
ligand, atom_indices[0], coords, conformer_index)
else:
direction = None
return PharmacophoricPoint(feat_type=feat_name,
center=puw.quantity(coords, "angstroms"),
radius=puw.quantity(radius, "angstroms"),
direction=direction,
atom_indices=atom_indices)
def pharmacophoric_points():
""" Returns a tuple with lists of 20 pharmacophoric points of the same kind."""
radius = puw.quantity(1.0, "angstroms")
donor_1 = []
for ii in range(20):
center = np.array([1.0, 0.0, 3.0]) + ii / 10
donor_1.append(
PharmacophoricPoint(feat_type="hb donor",
center=puw.quantity(center, "angstroms"),
radius=radius,
atom_indices=(1, )))
donor_2 = []
for ii in range(20):
center = np.array([-5.0, 1.5, -2.4]) + ii / 10
donor_2.append(
PharmacophoricPoint(feat_type="hb donor",
center=puw.quantity(center, "angstroms"),
radius=radius,
atom_indices=(8, )))
aromatic = []
for ii in range(20):
center = np.array([-5.0, 1.5, -2.4]) + ii / 10
aromatic.append(
PharmacophoricPoint(feat_type="aromatic ring",
center=puw.quantity(center, "angstroms"),
radius=radius,
atom_indices=(2, 3, 4, 5, 6, 7)))
acceptor = []
for ii in range(20):
center = np.array([-0.5, 8.5, 2.4]) + ii / 10
acceptor.append(
PharmacophoricPoint(feat_type="hb acceptor",
center=puw.quantity(center, "angstroms"),
radius=radius,
atom_indices=(10, )))
hydrophobic = []
for ii in range(20):
center = np.array([-0.5, 8.5, 2.4]) + ii / 10
hydrophobic.append(
PharmacophoricPoint(feat_type="hydrophobicity",
center=puw.quantity(center, "angstroms"),
radius=radius,
atom_indices=(12, )))
return (donor_1, donor_2, aromatic, acceptor, hydrophobic)
def test_distance_between_pharmacophoric_points():
radius = puw.quantity(1.0, "angstroms")
point_1 = PharmacophoricPoint("aromatic ring",
puw.quantity([3, 4, 0], "angstroms"), radius)
point_2 = PharmacophoricPoint("hb acceptor",
puw.quantity([0, 0, 0], "angstroms"), radius)
assert distance_bewteen_pharmacophoric_points(point_1, point_2) == 5
point_1 = PharmacophoricPoint("aromatic ring",
puw.quantity([1, 1, 1], "angstroms"), radius)
point_2 = PharmacophoricPoint("hb acceptor",
puw.quantity([1, 1, 1], "angstroms"), radius)
assert distance_bewteen_pharmacophoric_points(point_1, point_2) == 0
def three_point_pharmacophore() -> Pharmacophore:
"""Returns as pharmacophore with three pharmacophoric_points"""
hb_acceptor = PharmacophoricPoint(
feat_type="hb acceptor",
center=puw.quantity([1,0,0], "angstroms"),
radius=puw.quantity(1.0, "angstroms")
)
ring_1 = PharmacophoricPoint(
feat_type="aromatic ring",
center=puw.quantity([2, 1, 4], "angstroms"),
radius=puw.quantity(1.0, "angstroms")
)
ring_2 = PharmacophoricPoint(
feat_type="aromatic ring",
center=puw.quantity([0, 1, 2], "angstroms"),
radius=puw.quantity(1.0, "angstroms")
)
return Pharmacophore(pharmacophoric_points=[ring_1, hb_acceptor, ring_2])
def test_inmutable(three_point_pharmacophore):
# Test that we cannot modify the pharmacophoric point list
hydrophobicity = PharmacophoricPoint(
feat_type="hydrophobicity",
center=puw.quantity([-1, 0, 3], "angstroms"),
radius=puw.quantity(1.0, "angstroms")
)
with pytest.raises(TypeError):
three_point_pharmacophore[2] = hydrophobicity
def read_pharmagist(file_name: str) -> List[LigandBasedPharmacophore]:
""" Loads pharmacophores from a pharmagist mol2 file.
Parameters
----------
file_name : str
Name of the file containing the pharmacophore.
pharmacophore_index : int, optional
If given, returns the pharmacophore which index is provided.
Else, all the pharmcophores from the file will be returned.
Returns
-------
pharmacophores : list of openpharmacophore.LigandBasedPharmacophores
A list of ligand based pharmacophores.
"""
# dictionary to map pharmagist feature names to openpharmacophore pharmacophoric_points
pharmagist_element_name = {
"AR": "aromatic ring",
"HYD": "hydrophobicity",
"ACC": "hb acceptor",
"DON": "hb donor",
"CAT": "positive charge",
"ANI": "negative charge",
}
pharmacophores = []
pattern = r"[A-Z]{2,3} "
with open(file_name, "r") as f:
for line in f.readlines():
match = re.search(pattern, line)
if "@<TRIPOS>ATOM" in line:
points = []
if match:
point_line = [p for p in line.split(" ") if p != ""]
feat_type = pharmagist_element_name[point_line[1]]
center = [float(coord) for coord in point_line[2:5]
] # convert coordinates to float
center = puw.quantity(center, "angstroms")
element = PharmacophoricPoint(feat_type=feat_type,
center=center,
radius=puw.quantity(
1.0, "angstroms"))
insort_right(points, element, key=lambda p: p.short_name)
if "@<TRIPOS>BOND" in line:
pharmacophores.append(points)
pharmacophores = [ph for ph in pharmacophores
if len(ph) > 0] # filter empty lists
pharmacophores = [LigandBasedPharmacophore(ph) for ph in pharmacophores]
return pharmacophores
def four_element_pharmacophore():
pharmacophoric_points = [
PharmacophoricPoint(feat_type="hb acceptor",
center=puw.quantity([3.877, 7.014, 1.448],
"angstroms"),
radius=puw.quantity(1.0, "angstroms")),
PharmacophoricPoint(feat_type="hb acceptor",
center=puw.quantity([7.22, 11.077, 5.625],
"angstroms"),
radius=puw.quantity(1.0, "angstroms")),
PharmacophoricPoint(feat_type="hb donor",
center=puw.quantity([4.778, 8.432, 7.805],
"angstroms"),
radius=puw.quantity(1.0, "angstroms")),
PharmacophoricPoint(
feat_type="aromatic ring",
center=puw.quantity([1.56433333333334, 7.06399999999999, 3.135],
"angstroms"),
radius=puw.quantity(1.0, "angstroms"))
]
return Pharmacophore(pharmacophoric_points)
def test_pharmacophoric_point_extractor():
# Known points of acetic acid
acceptor = PharmacophoricPoint(
feat_type="hb acceptor",
center=puw.quantity(
[0.07903459193908467, 0.1487388014682705, 0.002355596284157232],
"nanometer"),
radius=puw.quantity(1.0, "angstroms"))
negative = PharmacophoricPoint(
feat_type="negative charge",
center=puw.quantity(
[0.08966065176585349, 0.03784658233931392, -0.01482808230401158],
"nanometer"),
radius=puw.quantity(1.0, "angstroms"))
acetic_acid = Chem.MolFromSmiles("CC(=O)O")
acetic_acid = utils.conformers.generate_conformers(acetic_acid,
1,
random_seed=1,
alignment=False)
extractor = PharmacophoricPointExtractor()
points = extractor(acetic_acid, 0)
assert len(points) == 3
assert acceptor.feature_name == points[0].feature_name
assert np.all(acceptor.center == points[0].center)
assert acceptor.radius == points[0].radius
rdkit_extractor = PharmacophoricPointExtractor(
featdef=rdkit_featuredefinition())
points = rdkit_extractor(acetic_acid, 0)
assert len(points) == 5
assert acceptor.feature_name == points[0].feature_name
assert np.all(acceptor.center == points[0].center)
assert acceptor.radius == points[0].radius
assert negative.feature_name == points[-1].feature_name
assert np.all(negative.center == points[-1].center)
assert negative.radius == points[-1].radius
def test_distance_matrix():
# Test pharmacophore with zero elements
pharmacophore = Pharmacophore()
matrix = pharmacophore.distance_matrix()
assert matrix.shape == (0, 0)
radius = puw.quantity(1.0, "angstroms")
points = [
PharmacophoricPoint(feat_type="hb acceptor",
center=puw.quantity([1, 0, -5], "angstroms"),
radius=radius),
PharmacophoricPoint(feat_type="hb donor",
center=puw.quantity([2, 1, 0], "angstroms"),
radius=radius),
PharmacophoricPoint(feat_type="aromatic ring",
center=puw.quantity([-3, 2, -1], "angstroms"),
radius=radius),
]
pharmacophore = Pharmacophore(pharmacophoric_points=points)
distance_matrix = pharmacophore.distance_matrix()
assert distance_matrix.shape == (3, 3)
assert np.allclose(distance_matrix,
np.array([[0, np.sqrt(27), 6],
[np.sqrt(27), 0, np.sqrt(27)],
[6, np.sqrt(27), 0]])
)
points = [
PharmacophoricPoint(feat_type="hb acceptor",
center=puw.quantity([1, 2, 3], "angstroms"),
radius=radius),
PharmacophoricPoint(feat_type="negative charge",
center=puw.quantity([0, 0, 0], "angstroms"),
radius=radius),
PharmacophoricPoint(feat_type="positive charge",
center=puw.quantity([-1, 0, -1], "angstroms"),
radius=radius),
PharmacophoricPoint(feat_type="aromatic ring",
center=puw.quantity([2, -1, 1], "angstroms"),
radius=radius),
]
sq = np.sqrt
pharmacophore = Pharmacophore(pharmacophoric_points=points)
distance_matrix = pharmacophore.distance_matrix()
assert distance_matrix.shape == (4, 4)
assert np.allclose(distance_matrix,
np.array([[0, sq(14), sq(24), sq(14)],
[sq(14), 0, sq(2), sq(6)],
[sq(24), sq(2), 0, sq(14)],
[sq(14), sq(6), sq(14), 0]]))
def remove_feature(self, feat_type: str) -> None:
""" Remove an especific feature type from the pharmacophore pharmacophoric_points list
Parameters
----------
feat_type : str
Name or type of the feature to be removed.
"""
feats = PharmacophoricPoint.get_valid_features()
if feat_type not in feats:
raise InvalidFeatureError(f"Cannot remove feature. \"{feat_type}\" is not a valid feature type")
temp_pharmacophoric_points = [element for element in self._pharmacophoric_points if element.feature_name != feat_type]
self._pharmacophoric_points = temp_pharmacophoric_points
self.n_pharmacophoric_points = len(self._pharmacophoric_points)
def _plip_hydrophobics(hydrophobics: List[PharmacophoricPoint],
radius: float) -> List[PharmacophoricPoint]:
""" Groups plip hydrophobic points that are to close into a single point.
Parameters
----------
hydrophobics : list of openpharmacophore.PharmacophoricPoint
List with the hydrophobic points.
Returns
-------
grouped_points : list of openpharmacophore.PharmacophoricPoint
List with the grouped points.
"""
grouped_points = []
skip = []
for inx, hyd1 in enumerate(hydrophobics):
if hyd1 in skip:
continue
centroid = hyd1.center
indices = hyd1.atom_indices
count = 0
hyd1_center = puw.get_value(hyd1.center, "angstroms")
for hyd2 in hydrophobics[inx + 1:]:
if hyd1 == hyd2:
skip.append(hyd2)
continue
hyd2_center = puw.get_value(hyd2.center, "angstroms")
distance = np.linalg.norm(hyd1_center - hyd2_center)
if distance <= 2.5:
centroid += hyd2.center
indices.union(hyd2.atom_indices)
count += 1
skip.append(hyd2)
if count > 0:
centroid /= (count + 1)
grouped_points.append(
PharmacophoricPoint(feat_type="hydrophobicity",
center=centroid,
radius=radius,
direction=None,
atom_indices=indices))
return grouped_points
def rdkit_to_point(
feat_name: str,
coords: np.ndarray,
radius: float,
direction: Optional[Sequence] = None,
atom_indices: Optional[Sequence] = None) -> PharmacophoricPoint:
""" Transform an rdkit feature point to an openpharmacophore pharmacophoric point.
Parameters
----------
feat_name : str
rdkit name of the feature point.
coords : numpy.ndarray; shape: (3, )
3D coordinates of the centroid of the feature.
radius : float
Lenght of the radius of the parmacohporic points.
direction : list, tuple, numpy.ndarray; shape:(3,)
Unit vector.
Returns
-------
openpharmacophore.PharmacophoricPoint
The pharmacophoric point.
"""
points = {
"Acceptor": "hb acceptor",
"Donor": "hb donor",
"Aromatic": "aromatic ring",
"Hydrophobe": "hydrophobicity",
"PosIonizable": "positive charge",
"NegIonizable": "negative charge",
}
return PharmacophoricPoint(feat_type=points[feat_name],
center=puw.quantity(coords, "angstroms"),
radius=puw.quantity(radius, "angstroms"),
direction=direction,
atom_indices=atom_indices)
def test_smarts_hydrophobics():
ligand = Chem.MolFromSmiles(
"CC1=CC(=CC(=C1OCCCC2=CC(=NO2)C)C)C3=NOC(=N3)C(F)(F)F")
ligand = generate_conformers(ligand, 1, random_seed=1)
hydrophobics = SBP()._smarts_hydrophobics(ligand, 1.0)
assert len(hydrophobics) == 3
hyd_1 = hydrophobics[0]
hyd_2 = hydrophobics[2]
hyd_2_center = puw.get_value(hyd_2.center, "angstroms")
hyd_2_radius = puw.get_value(hyd_2.radius, "angstroms")
assert hyd_1 == PharmacophoricPoint(feat_type="hydrophobicity",
center=puw.quantity(
(1.4268, -1.9841, -1.4186),
"angstroms"),
radius=puw.quantity(1.0, "angstroms"))
assert np.allclose(np.around(hyd_2_center, 3), (-2.130, -0.542, -0.479),
rtol=0,
atol=1e-04)
assert np.allclose(hyd_2_radius, hyd_2_radius, rtol=0, atol=1e-03)
def from_ligandscout(file_name: str) -> List[PharmacophoricPoint]:
""" Loads a pharmacophore from a ligandscout pml file.
Parameters
----------
file_name : str
Name of the file containing the pharmacophore.
Returns
-------
points : list of openpharmacophore.PharmacophoricPoints
A list of pharmacophoric pharmacophoric_points.
"""
tree = ET.parse(file_name)
pharmacophore = tree.getroot()
ligandscout_to_oph = { # dictionary to map ligandscout features to openpharmacophore pharmacophoric_points
"PI": "positive charge",
"NI": "negative charge",
"HBD": "hb donor",
"HBA": "hb acceptor",
"H": "hydrophobicity",
"AR": "aromatic ring",
"exclusion": "excluded volume"
}
points = []
for element in pharmacophore:
if element.tag == "point":
feat_name = element.attrib["name"]
for position in element:
coords = position.attrib
x = float(coords["x3"])
y = float(coords["y3"])
z = float(coords["z3"])
radius = float(coords["tolerance"])
point = PharmacophoricPoint(
feat_type=ligandscout_to_oph[feat_name],
center=puw.quantity([x, y, z], "angstroms"),
radius=puw.quantity(radius, "angstroms"))
insort_right(points, point, key=lambda p: p.short_name)
elif element.tag == "vector":
feat_name = element.attrib["name"]
for position in element:
if position.tag == "origin":
coords_1 = position.attrib
x_1 = float(coords_1["x3"])
y_1 = float(coords_1["y3"])
z_1 = float(coords_1["z3"])
radius_1 = float(coords_1["tolerance"])
elif position.tag == "target":
coords_2 = position.attrib
x_2 = float(coords_2["x3"])
y_2 = float(coords_2["y3"])
z_2 = float(coords_2["z3"])
radius_2 = float(coords_2["tolerance"])
point = PharmacophoricPoint(
feat_type=ligandscout_to_oph[feat_name],
center=puw.quantity([x_1, y_1, z_1], "angstroms"),
radius=puw.quantity(radius_1, "angstroms"),
direction=[x_2, y_2, z_2])
insort_right(points, point, key=lambda p: p.short_name)
elif element.tag == "plane":
feat_name = element.attrib["name"]
for position in element:
if position.tag == "position":
coords_1 = position.attrib
x_1 = float(coords_1["x3"])
y_1 = float(coords_1["y3"])
z_1 = float(coords_1["z3"])
radius_1 = float(coords_1["tolerance"])
center = np.array([x_1, y_1, z_1])
elif position.tag == "normal":
coords_2 = position.attrib
x_2 = float(coords_2["x3"])
y_2 = float(coords_2["y3"])
z_2 = float(coords_2["z3"])
radius_2 = float(coords_2["tolerance"])
point = PharmacophoricPoint(
feat_type=ligandscout_to_oph[feat_name],
center=puw.quantity(center, "angstroms"),
radius=puw.quantity(radius_1, "angstroms"),
direction=[x_2, y_2, z_2])
insort_right(points, point, key=lambda p: p.short_name)
elif element.tag == "volume":
feat_name = element.attrib["type"]
for position in element:
coords = position.attrib
x = float(coords["x3"])
y = float(coords["y3"])
z = float(coords["z3"])
radius = float(coords["tolerance"])
point = PharmacophoricPoint(
feat_type=ligandscout_to_oph[feat_name],
center=puw.quantity([x, y, z], "angstroms"),
radius=puw.quantity(radius, "angstroms"))
insort_right(points, point, key=lambda p: p.short_name)
return points
def from_moe(file_name: str) -> List[PharmacophoricPoint]:
""" Loads a pharmacophore from a MOE ph4 file.
Parameters
----------
file_name : str
Name of the file containing the pharmacophore.
Returns
-------
points : list of openpharmacophore.PharmacophoricPoint
A list of pharmacophoric points.
"""
moe_to_oph = {
"Cat": "positive charge",
"Ani": "negative charge",
"Don": "hb donor",
"Acc": "hb acceptor",
"Hyd": "hydrophobicity",
"Aro": "aromatic ring",
}
points = []
with open(file_name, "r") as f:
moe_ph4_string = f.read()
# pieces = re.split("\s", moe_ph4_string)
pieces = moe_ph4_string.split()
pattern = r"Don|Acc|Aro|Cat|Ani|Hyd"
# Index where the excluded volumes spheres coordinates, if any, start
exclusion_inx = None
for i, piece in enumerate(pieces):
if re.match(pattern, piece):
if len(piece) == 7:
# Double features have seven characters i.e Acc|Aro
feat_name_1 = piece[0: 3]
feat_name_2 = piece[4:]
# Coordinates are always two items after the feature name
x = float(pieces[i + 2])
y = float(pieces[i + 3])
z = float(pieces[i + 4])
radius = float(pieces[i + 5])
point_1 = PharmacophoricPoint(
feat_type=moe_to_oph[feat_name_1],
center=puw.quantity([x, y, z], "angstroms"),
radius=puw.quantity(radius, "angstroms")
)
point_2 = PharmacophoricPoint(
feat_type=moe_to_oph[feat_name_2],
center=puw.quantity([x, y, z], "angstroms"),
radius=puw.quantity(radius, "angstroms")
)
insort_right(points, point_1, key=lambda p: p.short_name)
insort_right(points, point_2, key=lambda p: p.short_name)
else:
# Regular features and
# features with weird names i.e Cat$mDon, Acc2
feat_name = piece[0:3]
# Coordinates are always two items after the feature name
x = float(pieces[i + 2])
y = float(pieces[i + 3])
z = float(pieces[i + 4])
radius = float(pieces[i + 5])
point = PharmacophoricPoint(
feat_type=moe_to_oph[feat_name],
center=puw.quantity([x, y, z], "angstroms"),
radius=puw.quantity(radius, "angstroms")
)
insort_right(points, point, key=lambda p: p.short_name)
if piece == "#volumesphere":
# Excluded volume spheres are 10 items after #volumesphere
exclusion_inx = i + 10
break
if exclusion_inx:
count = 1
for p in pieces[exclusion_inx :]:
if p == "#volume":
break
if count == 1:
x = float(p)
count += 1
elif count == 2:
y = float(p)
count += 1
elif count == 3:
z = float(p)
count += 1
elif count == 4:
radius = float(p)
excluded_sphere = PharmacophoricPoint(
feat_type="excluded volume",
center=puw.quantity([x, y, z], "angstroms"),
radius=puw.quantity(radius, "angstroms")
)
insort_right(points, excluded_sphere, key=lambda p: p.short_name)
count = 1
return points
def test_from_pdb(file_name, ligand_id, hydrophobics):
pdbs_path = "./openpharmacophore/data/pdb/"
file_path = os.path.join(pdbs_path, file_name + ".pdb")
pharmacophore = SBP().from_pdb(file_path,
radius=1.0,
ligand_id=ligand_id,
hydrophobics=hydrophobics)
if file_name == "1ncr":
assert len(pharmacophore) == 5
assert pharmacophore.molecular_system is not None
hyd_1 = PharmacophoricPoint(feat_type="hydrophobicity",
center=puw.quantity(
(42.4462, -1.1092, 122.6226),
"angstroms"),
radius=puw.quantity(1.0, "angstroms"))
assert hyd_1 == pharmacophore[0]
hyd_2 = PharmacophoricPoint(feat_type="hydrophobicity",
center=puw.quantity(
(37.699, 4.393, 122.609), "angstroms"),
radius=puw.quantity(1.0, "angstroms"))
assert hyd_2 == pharmacophore[1]
hyd_3 = PharmacophoricPoint(feat_type="hydrophobicity",
center=puw.quantity(
(35.827, 5.861, 123.815), "angstroms"),
radius=puw.quantity(1.0, "angstroms"))
assert hyd_3 == pharmacophore[2]
hyd_4 = PharmacophoricPoint(feat_type="hydrophobicity",
center=puw.quantity(
(45.46, 2.006, 123.421), "angstroms"),
radius=puw.quantity(1.0, "angstroms"))
assert hyd_4 == pharmacophore[3]
ring = PharmacophoricPoint(
feat_type="aromatic ring",
center=puw.quantity((38.0292, 4.3594, 123.7382), "angstroms"),
radius=puw.quantity(1.0, "angstroms"),
direction=np.array([-0.6702, -0.0512, -0.7404]))
assert ring == pharmacophore[4]
elif file_name == "2hz1":
assert len(pharmacophore) == 10
assert pharmacophore.molecular_system is not None
assert pharmacophore.ligand is None
# Acceptor
hb_acceptor = PharmacophoricPoint(
feat_type="hb acceptor",
center=puw.quantity((2.327, 3.574, 2.628), "angstroms"),
radius=puw.quantity(1.0, "angstroms"),
direction=np.array([-0.8834, 0.2719, 0.3816]))
# Hydrophobics
assert hb_acceptor == pharmacophore[0]
hyd = PharmacophoricPoint(feat_type="hydrophobicity",
center=puw.quantity(
(5.134, 11.9745, 11.8155), "angstroms"),
radius=puw.quantity(1.0, "angstroms"))
assert hyd == pharmacophore[1]
hyd = PharmacophoricPoint(feat_type="hydrophobicity",
center=puw.quantity((0.396, 6.793, 7.373),
"angstroms"),
radius=puw.quantity(1.0, "angstroms"))
assert hyd == pharmacophore[2]
hyd = PharmacophoricPoint(feat_type="hydrophobicity",
center=puw.quantity((11.724, 5.702, 7.226),
"angstroms"),
radius=puw.quantity(1.0, "angstroms"))
assert hyd == pharmacophore[3]
hyd = PharmacophoricPoint(feat_type="hydrophobicity",
center=puw.quantity((12.502, 7.731, 9.51),
"angstroms"),
radius=puw.quantity(1.0, "angstroms"))
assert hyd == pharmacophore[4]
hyd = PharmacophoricPoint(feat_type="hydrophobicity",
center=puw.quantity((7.62, 3.602, 4.389),
"angstroms"),
radius=puw.quantity(1.0, "angstroms"))
assert hyd == pharmacophore[5]
hyd = PharmacophoricPoint(feat_type="hydrophobicity",
center=puw.quantity((8.728, 11.736, 11.502),
"angstroms"),
radius=puw.quantity(1.0, "angstroms"))
assert hyd == pharmacophore[6]
# Negative charges
neg_sphere = PharmacophoricPoint(feat_type="negative charge",
center=puw.quantity(
(2.279, 2.6625, 3.2525),
"angstroms"),
radius=puw.quantity(1.0, "angstroms"))
assert neg_sphere == pharmacophore[8]
neg_sphere = PharmacophoricPoint(feat_type="negative charge",
center=puw.quantity(
(1.074, 4.8205, 7.3245),
"angstroms"),
radius=puw.quantity(1.0, "angstroms"))
assert neg_sphere == pharmacophore[9]
elif file_name == "2hzi":
assert len(pharmacophore) == 5
assert pharmacophore.molecular_system is not None
assert pharmacophore.ligand is None
acceptor = PharmacophoricPoint(
feat_type="hb acceptor",
center=puw.quantity((16.163, 12.126, 2.521), "angstroms"),
radius=puw.quantity(1.0, "angstroms"),
direction=np.array([-0.0991, 0.9107, 0.4011]))
assert acceptor == pharmacophore[0]
donor = PharmacophoricPoint(
feat_type="hb donor",
center=puw.quantity((13.988, 12.055, 2.867), "angstroms"),
radius=puw.quantity(1.0, "angstroms"),
direction=np.array([-0.1195, -0.9419, -0.3139]))
assert donor == pharmacophore[1]
hyd = PharmacophoricPoint(feat_type="hydrophobicity",
center=puw.quantity(
(10.418, 11.8007, 2.3763), "angstroms"),
radius=puw.quantity(1.0, "angstroms"))
assert hyd == pharmacophore[2]
hyd = PharmacophoricPoint(feat_type="hydrophobicity",
center=puw.quantity((21.7962, 17.734, 4.249),
"angstroms"),
radius=puw.quantity(1.0, "angstroms"))
assert hyd == pharmacophore[3]
hyd = PharmacophoricPoint(feat_type="hydrophobicity",
center=puw.quantity((17.506, 13.853, 3.414),
"angstroms"),
radius=puw.quantity(1.0, "angstroms"))
assert hyd == pharmacophore[4]
elif file_name == "1qku":
assert len(pharmacophore) == 6
assert pharmacophore.molecular_system is not None
assert pharmacophore.ligand is not None
# Acceptors
acceptor = PharmacophoricPoint(
feat_type="hb acceptor",
center=puw.quantity((100.598, 17.99, 25.704), "angstroms"),
radius=puw.quantity(1.0, "angstroms"),
direction=np.array([0.7872, -0.4533, 0.4182]))
assert acceptor == pharmacophore[0]
acceptor = PharmacophoricPoint(
feat_type="hb acceptor",
center=puw.quantity((109.61, 12.027, 22.746), "angstroms"),
radius=puw.quantity(1.0, "angstroms"),
direction=np.array([-0.5805, 0.431, 0.6908]))
assert acceptor == pharmacophore[1]
# Hydrophobics
hyd = PharmacophoricPoint(feat_type="hydrophobicity",
center=puw.quantity(
(107.379, 12.449, 24.419), "angstroms"),
radius=puw.quantity(1.0, "angstroms"))
assert hyd == pharmacophore[3]
hyd = PharmacophoricPoint(feat_type="hydrophobicity",
center=puw.quantity(
(107.2112, 12.5732, 22.1112),
"angstroms"),
radius=puw.quantity(1.0, "angstroms"))
assert hyd == pharmacophore[4]
# Rings
ring = PharmacophoricPoint(
feat_type="aromatic ring",
center=puw.quantity((102.8133, 16.7163, 24.5195), "angstroms"),
radius=puw.quantity(1.0, "angstroms"),
direction=np.array([0.0937, 0.4983, -0.8619]))
assert ring == pharmacophore[5]
def _sb_pharmacophore_points(
interactions,
radius: float,
ligand: Chem.Mol,
hydrophobics: str = "smarts") -> List[PharmacophoricPoint]:
"""Static method to obtain a list of pharmacophoric points for the protein-ligand complex.
Parameters
----------
interacions : plip.structure.preparation.PLInteraction
object containing all interacion data for a single ligand and a protein.
radius : float
Radius of the spheres of the pharmacophoric points.
ligand : rdkit.Chem.Mol
The ligand in from the protein-ligand complex.
hydrophobics : {"plip", "smarts"}
Can be "plip" or "smarts". If the former is chosen the hydrophobic points will
be retrieved from the interactions plip calculates. Else smarts patterns will be used.
Returns
-------
list of openpharmacophore.pharmacophoric_point.PharmacophoricPoint
A list of pharmacophoric points.
"""
radius = puw.quantity(radius, "angstroms")
# List with all interactions
interactions = interactions.all_itypes
# list of pharmacophoric_pharmacophoric_points
points = []
# list oh hydrophobic points
hydrophobic_points = []
for interaction in interactions:
interaction_name = type(interaction).__name__
if interaction_name == "pistack":
ligand_center = np.array(interaction.ligandring.center)
protein_center = np.array(interaction.proteinring.center)
direction = protein_center - ligand_center
atom_indices = {
atom.idx
for atom in interaction.ligandring.atoms
}
aromatic = PharmacophoricPoint(feat_type="aromatic ring",
center=puw.quantity(
ligand_center, "angstroms"),
radius=radius,
direction=direction,
atom_indices=atom_indices)
points.append(aromatic)
elif interaction_name == "hydroph_interaction":
if hydrophobics != "plip":
continue
center = puw.quantity(interaction.ligatom.coords, "angstroms")
atom_inx = {interaction.ligatom.idx}
hydrophobic = PharmacophoricPoint(feat_type="hydrophobicity",
center=center,
radius=radius,
direction=None,
atom_indices=atom_inx)
hydrophobic_points.append(hydrophobic)
elif interaction_name == "saltbridge":
if interaction.protispos:
# The ligand has a negative charge
center = puw.quantity(interaction.negative.center,
"angstroms")
atom_indices = {
atom.idx
for atom in interaction.negative.atoms
}
charge_sphere = PharmacophoricPoint(
feat_type="negative charge",
center=center,
radius=radius,
atom_indices=atom_indices)
else:
# The ligand has a positive charge
center = puw.quantity(interaction.positive.center,
"angstroms")
atom_indices = {
atom.idx
for atom in interaction.positive.atoms
}
charge_sphere = PharmacophoricPoint(
feat_type="positive charge",
center=center,
radius=radius,
atom_indices=atom_indices)
points.append(charge_sphere)
elif interaction_name == "hbond":
if interaction.protisdon:
# The ligand has an acceptor atom
ligand_acceptor_center = np.array(interaction.a.coords)
ligand_acceptor_inx = {interaction.a.idx}
protein_donor_center = np.array(interaction.d.coords)
direction = ligand_acceptor_center - protein_donor_center
acceptor = PharmacophoricPoint(
feat_type="hb acceptor",
center=puw.quantity(ligand_acceptor_center,
"angstroms"),
radius=radius,
direction=direction,
atom_indices=ligand_acceptor_inx)
points.append(acceptor)
else:
# The ligand has a donor atom
ligand_donor_center = np.array(interaction.d.coords)
ligand_donor_inx = {interaction.d.idx}
protein_acceptor_center = np.array(interaction.a.coords)
direction = protein_acceptor_center - ligand_donor_center
donor = PharmacophoricPoint(feat_type="hb donor",
center=puw.quantity(
ligand_donor_center,
"angstroms"),
radius=radius,
direction=direction,
atom_indices=ligand_donor_inx)
points.append(donor)
else:
# TODO: Incorporate other features such as halogenbonds, waterbridges and metal complexes
continue
# Remove duplicate points
points_filtered = []
for p in points:
if p not in points_filtered:
points_filtered.append(p)
# Group hydrophobic interactions within a distance of 2.5 angstroms
if len(hydrophobic_points) > 1:
hydrophobic_points = StructuredBasedPharmacophore._plip_hydrophobics(
hydrophobic_points, radius)
if hydrophobics == "smarts":
radius = puw.get_value(radius, "angstroms")
hydrophobic_points = StructuredBasedPharmacophore._smarts_hydrophobics(
ligand, radius)
return points_filtered + hydrophobic_points
def test_PharmacophoricPoint():
# First we test that it raises the correct exceptions when the input arguments
# are not valid
radius = puw.quantity(1.0, "angstroms")
center = puw.quantity([1.0, 1.0, 1.0], "angstroms")
# Test that center is validated correctly
with pytest.raises(exc.IsNotQuantityError,
match="center is not a quantity"):
PharmacophoricPoint(feat_type="hb donor",
center=[1, 2, 3],
radius=radius)
with pytest.raises(exc.WrongDimensionalityError,
match="center has dimensionality"):
PharmacophoricPoint(feat_type="hb donor",
center=puw.quantity([1.0, 1.0, 1.0], "seconds"),
radius=radius)
with pytest.raises(exc.BadShapeError, match="center has shape"):
PharmacophoricPoint(feat_type="hb donor",
center=puw.quantity([1.0, 1.0], "angstroms"),
radius=radius)
# Test for radius
with pytest.raises(exc.IsNotQuantityError,
match="radius is not a quantity"):
PharmacophoricPoint(feat_type="hb donor", center=center, radius=1.0)
with pytest.raises(exc.NegativeRadiusError,
match="radius must be a positive"):
PharmacophoricPoint(feat_type="hb donor",
center=center,
radius=puw.quantity(-1.0, "angstroms"))
with pytest.raises(exc.WrongDimensionalityError,
match="radius has dimensionality"):
PharmacophoricPoint(feat_type="hb donor",
center=center,
radius=puw.quantity(1.0, "seconds"))
# Test feature type
with pytest.raises(exc.InvalidFeatureType,
match="is not a valid feature type"):
PharmacophoricPoint(feat_type="rubber duck",
center=center,
radius=radius)
with pytest.raises(exc.OpenPharmacophoreTypeError,
match="atom_indices must be"):
PharmacophoricPoint(feat_type="hb donor",
center=center,
radius=radius,
atom_indices=1)
feat_name = "hb donor"
atom_inxs = (3, 4, 5, 6)
donor_1 = PharmacophoricPoint(feat_name, center, radius, None, atom_inxs)
donor_2 = PharmacophoricPoint(feat_name,
center,
radius,
direction=np.array([1.0, 1.0, 1.0]),
atom_indices=atom_inxs)
assert donor_1.has_direction == False
assert np.allclose(puw.get_value(donor_1.center, "angstroms"),
np.array([1.0, 1.0, 1.0]))
assert np.allclose(puw.get_value(donor_1.radius, "angstroms"), 1.0)
assert atom_inxs == (3, 4, 5, 6)
feat_name = "aromatic ring"
center = puw.quantity([1.5, -2.0, 3.2], "angstroms")
radius = puw.quantity(1.5, "angstroms")
direction = np.array([1.0, 1.0, 1.0])
atom_inxs = None
ring = PharmacophoricPoint(feat_name, center, radius, direction, atom_inxs)
assert ring.has_direction == True
assert ring.atom_indices is None
assert np.allclose(puw.get_value(ring.center, "angstroms"),
np.array([1.5, -2.0, 3.2]))
assert np.allclose(puw.get_value(ring.radius, "angstroms"), 1.5)
assert np.allclose(
ring.direction,
np.array([[1.0, 1.0, 1.0]]) /
np.linalg.norm(np.array([1.0, 1.0, 1.0])))
assert donor_1 != ring
assert donor_2 != donor_1
def from_pharmer(
pharmacophore_file: str,
load_mol_sys: bool = False
) -> Tuple[List[PharmacophoricPoint], Chem.Mol, Chem.Mol]:
""" Loads a pharmacophore from a pharmer json file
Parameters
----------
pharmacophore_file : str
name of the file containing the pharmacophore
load_mol_sys : bool
If true loads the molecular system associated to the pharmacophore (Default: False).
Returns
-------
points : list of openpharmacophore.PharmacophoricPoint
A list of pharmacophoric points.
molecular_system : rdkit.Chem.Mol
The molecular system associated with the pharmacophore. If there is no molecular system or
if load_mol_sys is set to false, None is returned.
ligand : rdkit.Chem.Mol
The ligand associeted to the pharmacophore in case there is one. If there is no ligand None is returnde.
"""
points = []
molecular_system = None
ligand = None
if pharmacophore_file.endswith('.json'):
with open(pharmacophore_file, "r") as fff:
pharmacophore = json.load(fff)
else:
raise NotImplementedError
for pharmer_element in pharmacophore['points']:
pharmer_feature_name = pharmer_element['name']
if pharmer_feature_name == 'Aromatic':
center, radius, direction = get_pharmer_element_properties(
pharmer_element, direction=True)
element = PharmacophoricPoint("aromatic ring", center, radius,
direction)
elif pharmer_feature_name == 'Hydrophobic':
center, radius = get_pharmer_element_properties(pharmer_element,
direction=False)
element = PharmacophoricPoint("hydrophobicity", center, radius)
elif pharmer_feature_name == 'HydrogenAcceptor':
center, radius, direction = get_pharmer_element_properties(
pharmer_element, direction=True)
element = PharmacophoricPoint("hb acceptor", center, radius,
direction)
elif pharmer_feature_name == "HydrogenDonor":
center, radius, direction = get_pharmer_element_properties(
pharmer_element, direction=True)
element = PharmacophoricPoint("hb donor", center, radius,
direction)
elif pharmer_feature_name == "PositiveIon":
center, radius = get_pharmer_element_properties(pharmer_element,
direction=False)
element = PharmacophoricPoint("positive charge", center, radius)
elif pharmer_feature_name == "NegativeIon":
center, radius = get_pharmer_element_properties(pharmer_element,
direction=False)
element = PharmacophoricPoint("negative charge", center, radius)
elif pharmer_feature_name == "ExclusionSphere":
center, radius = get_pharmer_element_properties(pharmer_element,
direction=False)
element = PharmacophoricPoint("excluded volume", center, radius)
elif pharmer_feature_name == 'InclusionSphere':
center, radius = get_pharmer_element_properties(pharmer_element,
direction=False)
element = PharmacophoricPoint("included volume", center, radius)
insort_right(points, element, key=lambda p: p.short_name)
if load_mol_sys:
has_ligand = "ligand" in pharmacophore and pharmacophore["ligand"] != ""
if has_ligand:
ligand = Chem.rdmolfiles.MolFromPDBBlock(pharmacophore["ligand"])
has_receptor = "receptor" in pharmacophore and pharmacophore[
"receptor"] != ""
if has_receptor:
receptor = Chem.rdmolfiles.MolFromPDBBlock(
pharmacophore["receptor"])
molecular_system = receptor
return points, molecular_system, ligand