def compute_pi_cation(ligand, receptor):
"""
Computes number of pi-cation interactions.
Returns a dictionary whose keys are of form
${MOLTYPE}-CHARGED_${STRUCTURE} where MOLTYPE is either "LIGAND" or
"RECEPTOR" and STRUCTURE is "ALPHA" or "BETA" or "OTHER".
Parameters
----------
ligand: PDB Object
small molecule to dock.
receptor: PDB Object
protein to dock agains.
"""
pi_cation = {
"PI-CATION_LIGAND-CHARGED_ALPHA": 0,
"PI-CATION_LIGAND-CHARGED_BETA": 0,
"PI-CATION_LIGAND-CHARGED_OTHER": 0,
"PI-CATION_RECEPTOR-CHARGED_ALPHA": 0,
"PI-CATION_RECEPTOR-CHARGED_BETA": 0,
"PI-CATION_RECEPTOR-CHARGED_OTHER": 0,
}
for aromatic in receptor.aromatic_rings:
for charged in ligand.charges:
if charged.positive == True: # so only consider positive charges
if charged.coordinates.dist_to(aromatic.center) < CATION_PI_CUTOFF:
# project the charged onto the plane of the aromatic
charge_projected = project_point_onto_plane(charged.coordinates, aromatic.plane_coeff)
if charge_projected.dist_to(aromatic.center) < aromatic.radius + PI_PADDING:
structure = receptor.all_atoms[aromatic.indices[0]].structure
if structure == "":
# since it could be interacting with a cofactor or something
structure = "OTHER"
key = "PI-CATION_LIGAND-CHARGED_" + structure
hashtable_entry_add_one(pi_cation, key)
for aromatic in ligand.aromatic_rings:
# now it's the ligand that has the aromatic group
for charged in receptor.charges:
if charged.positive: # so only consider positive charges
if charged.coordinates.dist_to(aromatic.center) < CATION_PI_CUTOFF:
charge_projected = project_point_onto_plane(charged.coordinates, aromatic.plane_coeff)
if charge_projected.dist_to(aromatic.center) < aromatic.radius + PI_PADDING:
structure = receptor.all_atoms[charged.indices[0]].structure
if structure == "":
# since it could be interacting with a cofactor or something
structure = "OTHER"
key = "PI-CATION_RECEPTOR-CHARGED_" + structure
hashtable_entry_add_one(pi_cation, key)
return pi_cation
def compute_pi_pi_stacking(ligand, receptor):
"""
Computes pi-pi interactions.
Returns a dictionary with keys of form STACKING_${STRUCTURE} where
STRUCTURE is "ALPHA" or "BETA" or "OTHER". Values are counts of the
number of such stacking interactions.
Parameters
----------
ligand: PDB Object.
small molecule to dock.
receptor: PDB Object
protein to dock agains.
"""
pi_stacking = {"STACKING_ALPHA": 0, "STACKING_BETA": 0, "STACKING_OTHER": 0}
for lig_aromatic in ligand.aromatic_rings:
for rec_aromatic in receptor.aromatic_rings:
dist = lig_aromatic.center.dist_to(rec_aromatic.center)
if dist < PI_PI_CUTOFF:
# so there could be some pi-pi interactions. Now, let's
# check for stacking interactions. Are the two pi's roughly
# parallel?
lig_aromatic_norm_vector = Point(
coords=np.array(
[lig_aromatic.plane_coeff[0], lig_aromatic.plane_coeff[1], lig_aromatic.plane_coeff[2]]
)
)
rec_aromatic_norm_vector = Point(
coords=np.array(
[rec_aromatic.plane_coeff[0], rec_aromatic.plane_coeff[1], rec_aromatic.plane_coeff[2]]
)
)
angle_between_planes = (
angle_between_points(lig_aromatic_norm_vector, rec_aromatic_norm_vector) * 180.0 / math.pi
)
if math.fabs(angle_between_planes - 0) < 30.0 or math.fabs(angle_between_planes - 180) < 30.0:
# so they're more or less parallel, it's probably pi-pi
# stacking now, since pi-pi are not usually right on
# top of each other. They're often staggered. So I don't
# want to just look at the centers of the rings and
# compare. Let's look at each of the atoms. do atom of
# the atoms of one ring, when projected onto the plane of
# the other, fall within that other ring?
# start by assuming it's not a pi-pi stacking interaction
pi_pi = False
for ligand_ring_index in lig_aromatic.indices:
# project the ligand atom onto the plane of the receptor ring
pt_on_receptor_plane = project_point_onto_plane(
ligand.all_atoms[ligand_ring_index].coordinates, rec_aromatic.plane_coeff
)
if pt_on_receptor_plane.dist_to(rec_aromatic.center) <= rec_aromatic.radius + PI_PADDING:
pi_pi = True
break
# TODO(rbharath): This if-else is confusing.
if pi_pi == False:
for receptor_ring_index in rec_aromatic.indices:
# project the ligand atom onto the plane of the receptor ring
pt_on_ligand_plane = project_point_onto_plane(
receptor.all_atoms[receptor_ring_index].coordinates, lig_aromatic.plane_coeff
)
if pt_on_ligand_plane.dist_to(lig_aromatic.center) <= lig_aromatic.radius + PI_PADDING:
pi_pi = True
break
if pi_pi == True:
structure = receptor.all_atoms[rec_aromatic.indices[0]].structure
if structure == "":
# since it could be interacting with a cofactor or something
structure = "OTHER"
key = "STACKING_" + structure
hashtable_entry_add_one(pi_stacking, key)
return pi_stacking
def compute_pi_t(ligand, receptor):
"""
Computes T-shaped pi-pi interactions.
Returns a dictionary with keys of form T-SHAPED_${STRUCTURE} where
STRUCTURE is "ALPHA" or "BETA" or "OTHER". Values are counts of the
number of such stacking interactions.
Parameters
----------
ligand: PDB Object.
small molecule to dock.
receptor: PDB Object
protein to dock agains.
"""
pi_t = {"T-SHAPED_ALPHA": 0, "T-SHAPED_BETA": 0, "T-SHAPED_OTHER": 0}
for lig_aromatic in ligand.aromatic_rings:
for rec_aromatic in receptor.aromatic_rings:
lig_aromatic_norm_vector = Point(
coords=np.array([lig_aromatic.plane_coeff[0], lig_aromatic.plane_coeff[1], lig_aromatic.plane_coeff[2]])
)
rec_aromatic_norm_vector = Point(
coords=np.array([rec_aromatic.plane_coeff[0], rec_aromatic.plane_coeff[1], rec_aromatic.plane_coeff[2]])
)
angle_between_planes = (
angle_between_points(lig_aromatic_norm_vector, rec_aromatic_norm_vector) * 180.0 / math.pi
)
if math.fabs(angle_between_planes - 90) < 30.0 or math.fabs(angle_between_planes - 270) < 30.0:
# so they're more or less perpendicular, it's probably a
# pi-edge interaction having looked at many structures, I
# noticed the algorithm was identifying T-pi reactions
# when the two rings were in fact quite distant, often
# with other atoms in between. Eye-balling it, requiring
# that at their closest they be at least 5 A apart seems
# to separate the good T's from the bad
min_dist = 100.0
for ligand_ind in lig_aromatic.indices:
ligand_at = ligand.all_atoms[ligand_ind]
for receptor_ind in rec_aromatic.indices:
receptor_at = receptor.all_atoms[receptor_ind]
dist = ligand_at.coordinates.dist_to(receptor_at.coordinates)
if dist < min_dist:
min_dist = dist
if min_dist <= 5.0:
# so at their closest points, the two rings come within
# 5 A of each other.
# okay, is the ligand pi pointing into the receptor
# pi, or the other way around? first, project the
# center of the ligand pi onto the plane of the
# receptor pi, and vs. versa
# This could be directional somehow, like a hydrogen
# bond.
pt_on_receptor_plane = project_point_onto_plane(lig_aromatic.center, rec_aromatic.plane_coeff)
pt_on_ligand_plane = project_point_onto_plane(rec_aromatic.center, lig_aromatic.plane_coeff)
# now, if it's a true pi-T interaction, this projected
# point should fall within the ring whose plane it's
# been projected into.
if (pt_on_receptor_plane.dist_to(rec_aromatic.center) <= rec_aromatic.radius + PI_PADDING) or (
pt_on_ligand_plane.dist_to(lig_aromatic.center) <= lig_aromatic.radius + PI_PADDING
):
# so it is in the ring on the projected plane.
structure = receptor.all_atoms[rec_aromatic.indices[0]].structure
if structure == "":
# since it could be interacting with a cofactor or something
structure = "OTHER"
key = "T-SHAPED_" + structure
hashtable_entry_add_one(pi_t, key)
return pi_t
def compute_pi_cation(ligand, receptor):
"""
Computes number of pi-cation interactions.
Returns a dictionary whose keys are of form
${MOLTYPE}-CHARGED_${STRUCTURE} where MOLTYPE is either "LIGAND" or
"RECEPTOR" and STRUCTURE is "ALPHA" or "BETA" or "OTHER".
Parameters
----------
ligand: PDB Object
small molecule to dock.
receptor: PDB Object
protein to dock agains.
"""
pi_cation = {
'PI-CATION_LIGAND-CHARGED_ALPHA': 0,
'PI-CATION_LIGAND-CHARGED_BETA': 0,
'PI-CATION_LIGAND-CHARGED_OTHER': 0,
'PI-CATION_RECEPTOR-CHARGED_ALPHA': 0,
'PI-CATION_RECEPTOR-CHARGED_BETA': 0,
'PI-CATION_RECEPTOR-CHARGED_OTHER': 0
}
for aromatic in receptor.aromatic_rings:
for charged in ligand.charges:
if charged.positive == True: # so only consider positive charges
if charged.coordinates.dist_to(
aromatic.center) < CATION_PI_CUTOFF:
# project the charged onto the plane of the aromatic
charge_projected = project_point_onto_plane(
charged.coordinates, aromatic.plane_coeff)
if (charge_projected.dist_to(aromatic.center) <
aromatic.radius + PI_PADDING):
structure = receptor.all_atoms[
aromatic.indices[0]].structure
if structure == "":
# since it could be interacting with a cofactor or something
structure = "OTHER"
key = "PI-CATION_LIGAND-CHARGED_" + structure
hashtable_entry_add_one(pi_cation, key)
for aromatic in ligand.aromatic_rings:
# now it's the ligand that has the aromatic group
for charged in receptor.charges:
if charged.positive: # so only consider positive charges
if charged.coordinates.dist_to(
aromatic.center) < CATION_PI_CUTOFF:
charge_projected = project_point_onto_plane(
charged.coordinates, aromatic.plane_coeff)
if (charge_projected.dist_to(aromatic.center) <
aromatic.radius + PI_PADDING):
structure = receptor.all_atoms[
charged.indices[0]].structure
if structure == "":
# since it could be interacting with a cofactor or something
structure = "OTHER"
key = "PI-CATION_RECEPTOR-CHARGED_" + structure
hashtable_entry_add_one(pi_cation, key)
return pi_cation
def compute_pi_pi_stacking(ligand, receptor):
"""
Computes pi-pi interactions.
Returns a dictionary with keys of form STACKING_${STRUCTURE} where
STRUCTURE is "ALPHA" or "BETA" or "OTHER". Values are counts of the
number of such stacking interactions.
Parameters
----------
ligand: PDB Object.
small molecule to dock.
receptor: PDB Object
protein to dock agains.
"""
pi_stacking = {
'STACKING_ALPHA': 0,
'STACKING_BETA': 0,
'STACKING_OTHER': 0
}
for lig_aromatic in ligand.aromatic_rings:
for rec_aromatic in receptor.aromatic_rings:
dist = lig_aromatic.center.dist_to(rec_aromatic.center)
if dist < PI_PI_CUTOFF:
# so there could be some pi-pi interactions. Now, let's
# check for stacking interactions. Are the two pi's roughly
# parallel?
lig_aromatic_norm_vector = Point(coords=np.array([
lig_aromatic.plane_coeff[0], lig_aromatic.plane_coeff[1],
lig_aromatic.plane_coeff[2]
]))
rec_aromatic_norm_vector = Point(coords=np.array([
rec_aromatic.plane_coeff[0], rec_aromatic.plane_coeff[1],
rec_aromatic.plane_coeff[2]
]))
angle_between_planes = (angle_between_points(
lig_aromatic_norm_vector, rec_aromatic_norm_vector) *
180.0 / math.pi)
if (math.fabs(angle_between_planes - 0) < 30.0
or math.fabs(angle_between_planes - 180) < 30.0):
# so they're more or less parallel, it's probably pi-pi
# stacking now, since pi-pi are not usually right on
# top of each other. They're often staggered. So I don't
# want to just look at the centers of the rings and
# compare. Let's look at each of the atoms. do atom of
# the atoms of one ring, when projected onto the plane of
# the other, fall within that other ring?
# start by assuming it's not a pi-pi stacking interaction
pi_pi = False
for ligand_ring_index in lig_aromatic.indices:
# project the ligand atom onto the plane of the receptor ring
pt_on_receptor_plane = project_point_onto_plane(
ligand.all_atoms[ligand_ring_index].coordinates,
rec_aromatic.plane_coeff)
if (pt_on_receptor_plane.dist_to(rec_aromatic.center)
<= rec_aromatic.radius + PI_PADDING):
pi_pi = True
break
# TODO(rbharath): This if-else is confusing.
if pi_pi == False:
for receptor_ring_index in rec_aromatic.indices:
# project the ligand atom onto the plane of the receptor ring
pt_on_ligand_plane = project_point_onto_plane(
receptor.all_atoms[receptor_ring_index].
coordinates, lig_aromatic.plane_coeff)
if (pt_on_ligand_plane.dist_to(lig_aromatic.center)
<= lig_aromatic.radius + PI_PADDING):
pi_pi = True
break
if pi_pi == True:
structure = receptor.all_atoms[
rec_aromatic.indices[0]].structure
if structure == "":
# since it could be interacting with a cofactor or something
structure = "OTHER"
key = "STACKING_" + structure
hashtable_entry_add_one(pi_stacking, key)
return pi_stacking
def compute_pi_t(ligand, receptor):
"""
Computes T-shaped pi-pi interactions.
Returns a dictionary with keys of form T-SHAPED_${STRUCTURE} where
STRUCTURE is "ALPHA" or "BETA" or "OTHER". Values are counts of the
number of such stacking interactions.
Parameters
----------
ligand: PDB Object.
small molecule to dock.
receptor: PDB Object
protein to dock agains.
"""
pi_t = {'T-SHAPED_ALPHA': 0, 'T-SHAPED_BETA': 0, 'T-SHAPED_OTHER': 0}
for lig_aromatic in ligand.aromatic_rings:
for rec_aromatic in receptor.aromatic_rings:
lig_aromatic_norm_vector = Point(coords=np.array([
lig_aromatic.plane_coeff[0], lig_aromatic.plane_coeff[1],
lig_aromatic.plane_coeff[2]
]))
rec_aromatic_norm_vector = Point(coords=np.array([
rec_aromatic.plane_coeff[0], rec_aromatic.plane_coeff[1],
rec_aromatic.plane_coeff[2]
]))
angle_between_planes = (angle_between_points(
lig_aromatic_norm_vector, rec_aromatic_norm_vector) * 180.0 /
math.pi)
if (math.fabs(angle_between_planes - 90) < 30.0
or math.fabs(angle_between_planes - 270) < 30.0):
# so they're more or less perpendicular, it's probably a
# pi-edge interaction having looked at many structures, I
# noticed the algorithm was identifying T-pi reactions
# when the two rings were in fact quite distant, often
# with other atoms in between. Eye-balling it, requiring
# that at their closest they be at least 5 A apart seems
# to separate the good T's from the bad
min_dist = 100.0
for ligand_ind in lig_aromatic.indices:
ligand_at = ligand.all_atoms[ligand_ind]
for receptor_ind in rec_aromatic.indices:
receptor_at = receptor.all_atoms[receptor_ind]
dist = ligand_at.coordinates.dist_to(
receptor_at.coordinates)
if dist < min_dist:
min_dist = dist
if min_dist <= 5.0:
# so at their closest points, the two rings come within
# 5 A of each other.
# okay, is the ligand pi pointing into the receptor
# pi, or the other way around? first, project the
# center of the ligand pi onto the plane of the
# receptor pi, and vs. versa
# This could be directional somehow, like a hydrogen
# bond.
pt_on_receptor_plane = project_point_onto_plane(
lig_aromatic.center, rec_aromatic.plane_coeff)
pt_on_ligand_plane = project_point_onto_plane(
rec_aromatic.center, lig_aromatic.plane_coeff)
# now, if it's a true pi-T interaction, this projected
# point should fall within the ring whose plane it's
# been projected into.
if ((pt_on_receptor_plane.dist_to(rec_aromatic.center) <=
rec_aromatic.radius + PI_PADDING)
or (pt_on_ligand_plane.dist_to(lig_aromatic.center)
<= lig_aromatic.radius + PI_PADDING)):
# so it is in the ring on the projected plane.
structure = receptor.all_atoms[
rec_aromatic.indices[0]].structure
if structure == "":
# since it could be interacting with a cofactor or something
structure = "OTHER"
key = "T-SHAPED_" + structure
hashtable_entry_add_one(pi_t, key)
return pi_t
