def eval_func(self, candidates, args):
""" :param candidates: Current population being evaluated.
"""
scores_list = []
scores = []
print "Calculating scores... "
for conformation in candidates:
score = 0.0
surf_area = 0.0
phobic_area = 0.0
philic_area = 0.0
e_score = 0.0
# Create PeptideBuilder structure for conformation
geo = Geometry.geometry(self.sequence[0])
geo.phi = conformation[0]
geo.psi_im1 = conformation[1]
if self.sequence[0] != "G" and self.sequence[0] != "P" and self.sequence[0] != "A":
if 0 in self.mod_dict:
geo.inputRotamers(self.mod_dict[0])
structure = PeptideBuilder.initialize_res(geo)
i = 2
j = 1
for aa in self.sequence[1:]:
geo = Geometry.geometry(aa)
geo.phi = conformation[i]
geo.psi_im1 = conformation[i + 1]
if aa != "G" and aa != "P" and aa != "A":
if j in self.mod_dict:
geo.inputRotamers(self.mod_dict[j])
j += 1
structure = PeptideBuilder.add_residue(structure, geo)
i += 2
out = Bio.PDB.PDBIO()
out.set_structure(structure)
out.save(self.path + "/msms/prot" + str(self.id) + ".pdb")
# Add hydrogens with pybel
mol = pybel.readfile("pdb", self.path + "/msms/prot" + str(self.id) + ".pdb").next()
mol.OBMol.AddHydrogens()
pybelmol = pybel.Molecule(mol)
pybelmol.write("pdb", self.path + "/msms/prot" + str(self.id) + ".pdb",
overwrite=True)
# Convert to xyzrn with msms executable
subprocess.call('cd ' + self.path + '/msms; ./pdb_to_xyzrn prot' + str(self.id) +
'.pdb > prot' + str(self.id) + '.xyzrn', shell=True)
# Enforce constraints (atoms can't come closer than van-der-waals radii)
check = []
with open(self.path + "/msms/prot" + str(self.id) + ".xyzrn") as f:
check = f.readlines()
atoms_check = []
unk = False
for atom in check:
entries = atom.split()
name = entries[5]
ent = name.split("_")
resid = ent[2]
atname = ent[0]
res = ent[1]
try:
r = get_radius(atname, res)[0]
except KeyError:
unk = True
score = 1000000
break
atoms_check.append([resid, entries[0], entries[1], entries[2], r, atname, res])
if not unk:
clash = False
for atom in atoms_check:
id1 = int(atom[0])
atname1 = atom[5]
x = float(atom[1])
y = float(atom[2])
z = float(atom[3])
r = float(atom[4])
for atom2 in atoms_check:
id2 = int(atom2[0])
atname2 = atom2[5]
if (id1 != id2) and not (((id2 == (id1 + 1)) or (id2 == (id1 - 1)))
and (((atname1 == "CA") or (atname1 == "C") or (atname1 == "N")) and
((atname2 == "CA") or (atname2 == "C") or (atname2 == "N")))):
x2 = float(atom2[1])
y2 = float(atom2[2])
z2 = float(atom2[3])
r2 = float(atom2[4])
distance = np.sqrt((x2 - x)**2 + (y2 - y)**2 + (z2 - z)**2)
if distance < r + r2:
solved = self.rebuild(id1, id2, self.rot_iter, conformation)
if not solved:
score = 1000000
clash = True
print "CLASH"
print "> " + str(atname1) + " " + str(atname2) + " " + str(distance) + " " + str(id1) + " " \
+ str(id2)
break
else:
print "Solved."
if clash:
break
if not clash:
# Compute ses for all atoms with msms executable
subprocess.call('cd ' + self.path + '/msms; ' +
'./msms.x86_64Linux2.2.6.1 -if prot' + str(self.id) + '.xyzrn -af ses_atoms' +
str(self.id) + ' > /dev/null', shell=True)
with open(self.path + "/msms/ses_atoms" + str(self.id) + ".area") as f:
atoms = f.readlines()
ses_type = []
for i in range(len(atoms)):
if i != 0:
entries = atoms[i].split()
ses = entries[1]
atom_desc = entries[3]
atmname = atom_desc.split("_")
rad_hydro = get_radius(atmname[0].strip(), atmname[1].strip())
res_num = atmname[2].strip()
atm_type = rad_hydro[1]
ses_type.append([ses, atm_type, res_num])
for atom in ses_type:
surf_area += float(atom[0])
if atom[1] == 1:
phobic_area += float(atom[0])
if atom[1] == 2:
philic_area -= float(atom[0])
print "SA: " + str(surf_area/2)
print "SPHOBE: " + str(phobic_area)
print "SPHIL: " + str(philic_area)
# print "ES: " + str(e_score)
# Score the new conformation
score = surf_area/2 + phobic_area + philic_area
scores.append([score, conformation])
# For fitness
scores_list.append(score)
print "Done. \n"
scores = sorted(scores)
# Save lowest to pdb
if scores[0][0] < self.lowest:
conformation = scores[0][1]
geo = Geometry.geometry(self.sequence[0])
geo.phi = conformation[0]
geo.psi_im1 = conformation[1]
if self.sequence[0] != "G" and self.sequence[0] != "P" and self.sequence[0] != "A":
if 0 in self.mod_dict:
geo.inputRotamers(self.mod_dict[0])
structure = PeptideBuilder.initialize_res(geo)
i = 2
j = 1
for aa in self.sequence[1:]:
geo = Geometry.geometry(aa)
geo.phi = conformation[i]
geo.psi_im1 = conformation[i + 1]
if aa != "G" and aa != "P" and aa != "A":
if j in self.mod_dict:
geo.inputRotamers(self.mod_dict[j])
j += 1
structure = PeptideBuilder.add_residue(structure, geo)
i += 2
out = Bio.PDB.PDBIO()
out.set_structure(structure)
out.save("lowest" + str(self.id) + ".pdb")
mol = pybel.readfile("pdb", "lowest" + str(self.id) + ".pdb").next()
mol.OBMol.AddHydrogens()
pybelmol = pybel.Molecule(mol)
pybelmol.write("pdb", "lowest" + str(self.id) + ".pdb", overwrite=True)
pybelmol.write("pdb", "lowest_backup" + str(self.id) + ".pdb", overwrite=True)
if scores[0][0] < self.lowest:
self.lowest = scores[0][0]
print "Lowest score: " + str(self.lowest)
# return novelty_scores
return scores_list
def local_mover(self, n):
""" :param candidates: Current population being evaluated.
"""
conformation = self.conformation
move = 0
score = 0.0
surf_area = 0.0
phobic_area = 0.0
philic_area = 0.0
e_score = 0.0
if self.steps != 0:
rand = random.random()
if rand < 0.33:
move = -self.mover_size
elif rand < 0.66:
move = 0
else:
move = self.mover_size
conformation[n] += move
geo = Geometry.geometry(self.sequence[0])
geo.phi = conformation[0]
geo.psi_im1 = conformation[1]
if self.sequence[0] != "G" and self.sequence[0] != "P" and self.sequence[0] != "A":
if 0 in self.mod_dict:
geo.inputRotamers(self.mod_dict[0])
structure = PeptideBuilder.initialize_res(geo)
i = 2
j = 1
for aa in self.sequence[1:]:
geo = Geometry.geometry(aa)
geo.phi = conformation[i]
geo.psi_im1 = conformation[i + 1]
if aa != "G" and aa != "P" and aa != "A":
if j in self.mod_dict:
geo.inputRotamers(self.mod_dict[j])
j += 1
structure = PeptideBuilder.add_residue(structure, geo)
i += 2
out = Bio.PDB.PDBIO()
out.set_structure(structure)
out.save(self.path + "/msms/prot" + str(self.id) + ".pdb")
mol = pybel.readfile("pdb", self.path + "/msms/prot" + str(self.id) + ".pdb").next()
mol.OBMol.AddHydrogens()
pybelmol = pybel.Molecule(mol)
pybelmol.write("pdb", self.path + "/msms/prot" + str(self.id) + ".pdb",
overwrite=True)
subprocess.call('cd ' + self.path + '/msms; ./pdb_to_xyzrn prot' + str(self.id) +
'.pdb > prot' + str(self.id) + '.xyzrn', shell=True)
check = []
with open(self.path + "/msms/prot" + str(self.id) + ".xyzrn") as f:
check = f.readlines()
atoms_check = []
unk = False
for atom in check:
entries = atom.split()
name = entries[5]
ent = name.split("_")
resid = ent[2]
atname = ent[0]
res = ent[1]
try:
r = get_radius(atname, res)[0]
except KeyError:
unk = True
score = 1000000
break
atoms_check.append([resid, entries[0], entries[1], entries[2], r, atname, res])
if not unk:
clash = False
for atom in atoms_check:
id1 = int(atom[0])
atname1 = atom[5]
x = float(atom[1])
y = float(atom[2])
z = float(atom[3])
r = float(atom[4])
for atom2 in atoms_check:
id2 = int(atom2[0])
atname2 = atom2[5]
if (id1 != id2) and not (((id2 == (id1 + 1)) or (id2 == (id1 - 1)))
and (((atname1 == "CA") or (atname1 == "C") or (atname1 == "N")) and
((atname2 == "CA") or (atname2 == "C") or (atname2 == "N")))):
x2 = float(atom2[1])
y2 = float(atom2[2])
z2 = float(atom2[3])
r2 = float(atom2[4])
distance = np.sqrt((x2 - x)**2 + (y2 - y)**2 + (z2 - z)**2)
if distance < r + r2:
solved = self.rebuild(id1, id2, self.rot_iter, conformation)
if not solved:
score = 1000000
clash = True
print "CLASH"
print "> " + str(atname1) + " " + str(atname2) + " " + str(distance) + " " + str(id1) + " " \
+ str(id2)
break
else:
print "Solved."
if clash:
break
if not clash:
self.threshold = 0
subprocess.call('cd ' + self.path + '/msms; ' +
'./msms.x86_64Linux2.2.6.1 -if prot' + str(self.id) + '.xyzrn -af ses_atoms' +
str(self.id) + ' > /dev/null', shell=True)
with open(self.path + "/msms/ses_atoms" + str(self.id) + ".area") as f:
atoms = f.readlines()
ses_type = []
for i in range(len(atoms)):
if i != 0:
entries = atoms[i].split()
ses = entries[1]
atom_desc = entries[3]
atmname = atom_desc.split("_")
rad_hydro = get_radius(atmname[0].strip(), atmname[1].strip())
res_num = atmname[2].strip()
atm_type = rad_hydro[1]
ses_type.append([ses, atm_type, res_num])
for atom in ses_type:
surf_area += float(atom[0])
if atom[1] == 1:
phobic_area += float(atom[0])
if atom[1] == 2:
philic_area -= float(atom[0])
print "SA: " + str(surf_area)
print "SPHOBE: " + str(phobic_area)
# print "SPHIL: " + str(philic_area)
# print "ES: " + str(e_score)
# Score the new conformation
score = surf_area + phobic_area
if self.steps == 0:
self.current_score = score
self.accepted += 1
else:
if score >= self.current_score:
try:
p_acc = math.exp(-(score - self.current_score)/self.temperature)
print "PACC " + str(p_acc)
except OverflowError:
p_acc = 0
print "OVERFLOW"
rand = random.random()
if p_acc < rand:
self.rejected += 1
pass
else:
self.conformation = conformation
self.current_score = score
self.accepted += 1
else:
self.conformation = conformation
self.current_score = score
self.accepted += 1
if score < self.lowest:
self.lowest = score
pybelmol.write("pdb", "lowest" + str(self.id) + ".pdb", overwrite=True)
pybelmol.write("pdb", "lowest_backup" + str(self.id) + ".pdb", overwrite=True)
# For messing with dynamic parameter adjustment
# if self.threshold % 10 == 0:
# if self.mover_size > 1:
# self.mover_size -= 1
# print "MS: " + str(self.mover_size)
# self.threshold = 0
# if self.steps % 20 == 0:
# if self.lowest - self.score_10 < 10:
# self.mover_size += 1
# self.score_10 = self.lowest
print "Done. \n"
print "################################"
print "Step " + str(self.steps) + " | MC Ratio: " + str(self.rejected/self.accepted) + \
" | Lowest score: " + str(self.lowest)
print "################################"
self.steps += 1
def rebuild(self, id1, id2, it, conformation):
"""Rebuilds clashing residues.
:param id1: First residue id.
:param id2: Second residue id.
:param it: Number of iterations.
:param conformation: Current conformation.
:return: :type boolean: True if successfully rebuilt, False if not.
"""
print "Adjusting rotamers..."
new_rot1 = []
new_rot2 = []
aa1 = self.sequence[id1 - 1]
aa2 = self.sequence[id2 - 1]
solved = False
if (aa1 != "G" and aa1 != "P" and aa1 != "A") or (aa2 != "G" and aa2 != "P" and aa2 != "A"):
for n in range(it):
if solved:
break
if n == 0:
new_rot1 = self.make_rot_list(aa1)
new_rot2 = self.make_rot_list(aa2)
else:
moves1 = []
for j in range(len(new_rot1)):
rand = random.random()
if rand < 0.33:
moves1.append(-self.rot_mover_size)
elif rand < 0.66:
moves1.append(0)
else:
moves1.append(self.rot_mover_size)
new_rot1 = [new_rot1[i] + moves1[i] for i in range(len(new_rot1))]
moves2 = []
for j in range(len(new_rot2)):
rand = random.random()
if rand < 0.33:
moves2.append(-self.rot_mover_size)
elif rand < 0.66:
moves2.append(0)
else:
moves2.append(self.rot_mover_size)
new_rot2 = [new_rot2[i] + moves2[i] for i in range(len(new_rot2))]
geo = Geometry.geometry(self.sequence[0])
geo.phi = conformation[0]
geo.psi_im1 = conformation[1]
if id1 - 1 == 0:
if aa1 != "G" and aa1 != "P" and aa1 != "A":
geo.inputRotamers(new_rot1)
elif id2 - 1 == 0:
if aa2 != "G" and aa2 != "P" and aa2 != "A":
geo.inputRotamers(new_rot2)
elif 0 in self.mod_dict:
if self.sequence[0] != "G" and self.sequence[0] != "P" and self.sequence[0] != "A":
geo.inputRotamers(self.mod_dict[0])
structure = PeptideBuilder.initialize_res(geo)
i = 2
j = 1
for aa in self.sequence[1:]:
geo = Geometry.geometry(aa)
geo.phi = conformation[i]
geo.psi_im1 = conformation[i + 1]
if id1 == j + 1:
if aa1 != "G" and aa1 != "P" and aa1 != "A":
geo.inputRotamers(new_rot1)
elif id2 == j + 1:
if aa2 != "G" and aa2 != "P" and aa2 != "A":
geo.inputRotamers(new_rot2)
elif j in self.mod_dict:
geo.inputRotamers(self.mod_dict[j])
j += 1
structure = PeptideBuilder.add_residue(structure, geo)
i += 2
out = Bio.PDB.PDBIO()
out.set_structure(structure)
out.save(self.path + "/msms/prot" + str(self.id) + ".pdb")
mol = pybel.readfile("pdb", self.path + "/msms/prot" + str(self.id) + ".pdb").next()
mol.OBMol.AddHydrogens()
pybelmol = pybel.Molecule(mol)
pybelmol.write("pdb", self.path + "/msms/prot" + str(self.id) + ".pdb",
overwrite=True)
subprocess.call('cd ' + self.path + '/msms; ./pdb_to_xyzrn prot' + str(self.id) +
'.pdb > prot' + str(self.id) + '.xyzrn', shell=True)
check = []
with open(self.path + "/msms/prot" + str(self.id) + ".xyzrn") as f:
check = f.readlines()
atoms_check = []
clash = False
unk = False
for atom in check:
entries = atom.split()
name = entries[5]
ent = name.split("_")
resid = ent[2]
atname = ent[0]
res = ent[1]
try:
r = get_radius(atname, res)[0]
except KeyError:
unk = True
break
atoms_check.append([resid, entries[0], entries[1], entries[2], r, atname, res])
if not unk:
for atom in atoms_check:
aid1 = int(atom[0])
atname1 = atom[5]
x = float(atom[1])
y = float(atom[2])
z = float(atom[3])
r = float(atom[4])
for atom2 in atoms_check:
aid2 = int(atom2[0])
atname2 = atom2[5]
if (aid1 != aid2) and not (((aid2 == (aid1 + 1)) or (aid2 == (aid1 - 1)))
and (((atname1 == "CA") or (atname1 == "C") or (atname1 == "N")) and
((atname2 == "CA") or (atname2 == "C") or (atname2 == "N")))):
x2 = float(atom2[1])
y2 = float(atom2[2])
z2 = float(atom2[3])
r2 = float(atom2[4])
distance = np.sqrt((x2 - x)**2 + (y2 - y)**2 + (z2 - z)**2)
if distance < r + r2:
clash = True
break
if clash:
break
if not clash:
solved = True
else:
print str(aa1) + " " + str(aa2)
if solved:
if aa1 != "G" and aa1 != "P" and aa1 != "A":
self.mod_dict[id1 - 1] = new_rot1
if aa2 != "G" and aa2 != "P" and aa2 != "A":
self.mod_dict[id2 - 1] = new_rot2
return True
else:
return False
def rotamer_mover(self, conformation, n):
if n == 0:
self.rot_conf_local = self.rot_conformation
for i in range(len(self.rot_conf_local)):
aa = self.rot_conf_local[i]
moves = []
for j in range(len(aa)):
rand = random.random()
if rand < 0.33:
moves.append(-self.rot_mover_size)
elif rand < 0.66:
moves.append(0)
else:
moves.append(self.rot_mover_size)
aa = [aa[i] + moves[i] for i in range(len(aa))]
self.rot_conf_local[i] = aa
geo = Geometry.geometry(self.sequence[0])
geo.phi = conformation[0]
geo.psi_im1 = conformation[1]
geo.inputRotamers(self.rot_conf_local[0])
structure = PeptideBuilder.initialize_res(geo)
i = 2
j = 1
for aa in self.sequence[1:]:
geo = Geometry.geometry(aa)
geo.phi = conformation[i]
geo.psi_im1 = conformation[i + 1]
if aa != "G" and aa != "P" and aa != "A":
geo.inputRotamers(self.rot_conf_local[j])
j += 1
structure = PeptideBuilder.add_residue(structure, geo)
i += 2
out = Bio.PDB.PDBIO()
out.set_structure(structure)
out.save(self.path + "/msms/prot" + str(self.id) + ".pdb")
mol = pybel.readfile("pdb", self.path + "/msms/prot" + str(self.id) + ".pdb").next()
mol.OBMol.AddHydrogens()
pybelmol = pybel.Molecule(mol)
pybelmol.write("pdb", self.path + "/msms/prot" + str(self.id) + ".pdb",
overwrite=True)
subprocess.call('cd ' + self.path + '/msms; ./pdb_to_xyzrn prot' + str(self.id) +
'.pdb > prot' + str(self.id) + '.xyzrn', shell=True)
check = []
with open(self.path + "/msms/prot" + str(self.id) + ".xyzrn") as f:
check = f.readlines()
atoms_check = []
for atom in check:
entries = atom.split()
name = entries[5]
ent = name.split("_")
resid = ent[2]
atname = ent[0]
res = ent[1]
try:
r = get_radius(atname, res)[0]
except KeyError:
self.threshold += 1
return False
atoms_check.append([resid, entries[0], entries[1], entries[2], r, atname, res])
for atom in atoms_check:
id1 = int(atom[0])
atname1 = atom[5]
x = float(atom[1])
y = float(atom[2])
z = float(atom[3])
r = float(atom[4])
for atom2 in atoms_check:
id2 = int(atom2[0])
atname2 = atom2[5]
if (id1 != id2) and not (((id2 == (id1 + 1)) or (id2 == (id1 - 1)))
and (((atname1 == "CA") or (atname1 == "C") or (atname1 == "N")) and
((atname2 == "CA") or (atname2 == "C") or (atname2 == "N")))):
x2 = float(atom2[1])
y2 = float(atom2[2])
z2 = float(atom2[3])
r2 = float(atom2[4])
distance = np.sqrt((x2 - x)**2 + (y2 - y)**2 + (z2 - z)**2)
if distance < r + r2:
self.threshold += 1
self.rot_conformation = self.rot_conf_local
self.new_conf = True
print "Success."
return True
