def Model_Mutations_old(pdbfile,
mol2files,
mutations,
max_overlap=0.5,
return_score=False):
"""Model a number of mutations in a pdbfile when one or more ligands are present"""
#
# Initialise mutate routines
#
MUT = Mutate(max_bump=max_overlap)
#
# Read PDB file
#
import Protool
P = Protool.structureIO()
P.readpdb(pdbfile)
P.remove_all_hydrogens()
#
# Read mol2 file
#
L = Protool.ligand(P)
for mol2file in mol2files:
print "Added %s with tag 'LIGAND'" % mol2file
L.readmol2(mol2file, tag='LIGAND')
#
# Pass combined pdb file to mutate routines and mutate
#
MUT.new_PDB(P)
import pKa.pKD_tools as pKD_tools
total_bump = 0.0
#
# Model
#
for mutation in mutations:
#
# Get info
#
resid = pKD_tools.get_resid_from_mut(mutation)
newres = pKD_tools.get_newrestyp_from_mut(mutation)
oldres = pKD_tools.get_oldrestyp_from_mut(mutation)
bump_score = MUT.mutate(resid, newres, orgtype=oldres)
if bump_score is None or bump_score is False or bump_score > max_overlap:
print 'Cannot model this set of mutations - too many bumps'
return False, 20.0
print 'Bump score for %s: %5.3f' % (mutation, bump_score)
total_bump = total_bump + bump_score
print 'Total bump score for all mutations: %5.3f' % (bump_score)
if return_score:
return MUT, bump_score
return MUT
def Model_Mutations_old(pdbfile,mol2files,mutations,max_overlap=0.5,return_score=False):
"""Model a number of mutations in a pdbfile when one or more ligands are present"""
#
# Initialise mutate routines
#
MUT=Mutate(max_bump=max_overlap)
#
# Read PDB file
#
import Protool
P=Protool.structureIO()
P.readpdb(pdbfile)
P.remove_all_hydrogens()
#
# Read mol2 file
#
L=Protool.ligand(P)
for mol2file in mol2files:
print "Added %s with tag 'LIGAND'" %mol2file
L.readmol2(mol2file,tag='LIGAND')
#
# Pass combined pdb file to mutate routines and mutate
#
MUT.new_PDB(P)
import pKa.pKD_tools as pKD_tools
total_bump=0.0
#
# Model
#
for mutation in mutations:
#
# Get info
#
resid=pKD_tools.get_resid_from_mut(mutation)
newres=pKD_tools.get_newrestyp_from_mut(mutation)
oldres=pKD_tools.get_oldrestyp_from_mut(mutation)
bump_score=MUT.mutate(resid,newres,orgtype=oldres)
if bump_score is None or bump_score is False or bump_score>max_overlap:
print 'Cannot model this set of mutations - too many bumps'
return False,20.0
print 'Bump score for %s: %5.3f' %(mutation,bump_score)
total_bump=total_bump+bump_score
print 'Total bump score for all mutations: %5.3f' %(bump_score)
if return_score:
return MUT,bump_score
return MUT
def Model_Mutations(pdbfile,
mol2files,
mutations,
max_overlap=0.5,
max_totalbump=1.0,
return_score=False,
store_mutation_operations=False):
"""Model a number of mutations in a pdbfile when one or more ligands are present"""
#
# Check for stupidity
#
if max_overlap > max_totalbump:
max_totalbump = max_overlap
print 'Adjusted total bump cutoff to %5.2f' % max_totalbump
#
# Read PDB file
#
import Protool
P = Protool.structureIO()
P.readpdb(pdbfile)
P.remove_all_hydrogens()
#
# Read mol2 file
#
L = Protool.ligand(P)
for mol2file in mol2files:
print "Added %s with tag 'LIGAND'" % mol2file
L.readmol2(mol2file, tag='LIGAND')
#
# Get the pdb lines
#
pdblines = P.writepdb('junk.pdb', nowrite=True)
#
# Pass the lines to FFF
#
import FFF.FFFcontrol
myFFF = FFF.FFFcontrol.FFF()
myFFF.parse_lines(pdblines)
#myFFF.soup_stat()
Model = FFF.FFFcontrol.model_class(myFFF, Rotamerlib, FFFaadef_dir)
#
# Store the wild type PDB file
#
if store_mutation_operations:
wt_lines = myFFF.make_pdblines('PDB')
#
import pKa.pKD_tools as pKD_tools
total_bump = 0.0
for mutation in mutations:
resid = pKD_tools.get_resid_from_mut(mutation)
chainid = resid.split(':')[0]
resid = resid.split(':')[1]
#
# Get rid of the leading zeros
#
done = False
while not done:
if resid[0] == '0' and len(resid) > 1:
resid = resid[1:]
else:
done = True
#
newres = pKD_tools.get_newrestyp_from_mut(mutation)
oldres = pKD_tools.get_oldrestyp_from_mut(mutation)
opttype = 3 # Rotamer library
energies = Model.Mutate(chainid, resid, newres, opttype, max_overlap)
bump_score = energies[0]
Sum = energies[1]
Coulomb = energies[2]
#
total_bump = total_bump + bump_score
print 'Bump score: %5.2f, total bump: %5.2f' % (bump_score, total_bump)
if bump_score > max_overlap or total_bump > max_totalbump:
print 'Cannot model this set of mutations - too many bumps'
if return_score:
return False, total_bump
else:
return False
print 'Bump score for %s: %5.3f' % (mutation, bump_score)
print 'Total bump score for all mutations: %5.3f' % (total_bump)
class FFF_fix:
def __init__(self, FFF):
self.PI = FFF
return
#
# Create the instance
#
FFF_instance = FFF_fix(myFFF)
#
# Keep track of the changes that were made to the PDB file
#
if store_mutation_operations:
mut_lines = FFF_instance.PI.make_pdblines('PDB')
import Protool
WT = Protool.structureIO()
WT.parsepdb(wt_lines)
wt_atoms = sorted(WT.atoms.keys())
#
MUT = Protool.structureIO()
MUT.parsepdb(mut_lines)
#
mut_atoms = sorted(MUT.atoms.keys())
wt_count = 0
mutcount = 0
def coord_diff(atom1, atom2):
diff = 0.0
for coord in ['X', 'Y', 'Z']:
diff = diff + abs(atom1[coord] - atom2[coord])
return diff
operations = []
for atom in wt_atoms:
if not atom in mut_atoms:
operations.append(['delete', atom, WT.atoms[atom]])
elif coord_diff(WT.atoms[atom], MUT.atoms[atom]) > 0.1:
operations.append(['delete', atom, WT.atoms[atom]])
operations.append(['add', atom, MUT.atoms[atom]])
else:
pass
for atom in mut_atoms:
if not atom in wt_atoms:
operations.append(['add', atom, MUT.atoms[atom]])
#
# Store these in FFF_fix
#
FFF_instance.mutate_operations = operations[:]
#
# Return the info
#
if (return_score):
return FFF_instance, total_bump
return FFF_instance
# Build hydrogens
import Protool.hydrogens
H=Protool.hydrogens.Hydrogens(P)
H.build_all_HNs()
#
# Assign charges
#
import Protool.assign_parameters
PQR=Protool.assign_parameters.assign_parameters(P)
PQR.clear_all_charges_and_radii()
PQR.set_all_radii()
#
# Try loading a ligand
#
import Protool.ligand
L=Protool.ligand(P)
L.readmol2('substrate_natural.mol2') # Charges are already set
PQR.set_all_radii()
tot=0.0
for residue in P.chains['L']:
for atom in P.residues[residue]:
tot=tot+P.atoms[atom]['CHARGE']
print 'Total charge on ligand before any modification; %5.1f' %tot
BEFORE=APBS_calc(P,pdie=2.0)
#
# Now change the charge
#
charge_atom='L:0001:C1'
P.atoms[charge_atom]['CHARGE']=1.0
AFTER=APBS_calc(P,pdie=2.0)
# Build hydrogens
import Protool.hydrogens
H = Protool.hydrogens.Hydrogens(P)
H.build_all_HNs()
#
# Assign charges
#
import Protool.assign_parameters
PQR = Protool.assign_parameters.assign_parameters(P)
PQR.clear_all_charges_and_radii()
PQR.set_all_radii()
#
# Try loading a ligand
#
import Protool.ligand
L = Protool.ligand(P)
L.readmol2('substrate_natural.mol2') # Charges are already set
PQR.set_all_radii()
tot = 0.0
for residue in P.chains['L']:
for atom in P.residues[residue]:
tot = tot + P.atoms[atom]['CHARGE']
print 'Total charge on ligand before any modification; %5.1f' % tot
BEFORE = APBS_calc(P, pdie=2.0)
#
# Now change the charge
#
charge_atom = 'L:0001:C1'
P.atoms[charge_atom]['CHARGE'] = 1.0
AFTER = APBS_calc(P, pdie=2.0)
def Model_Mutations(pdbfile,mol2files,mutations,max_overlap=0.5,max_totalbump=1.0,return_score=False,store_mutation_operations=False):
"""Model a number of mutations in a pdbfile when one or more ligands are present"""
#
# Check for stupidity
#
if max_overlap>max_totalbump:
max_totalbump=max_overlap
print 'Adjusted total bump cutoff to %5.2f' %max_totalbump
#
# Read PDB file
#
import Protool
P=Protool.structureIO()
P.readpdb(pdbfile)
P.remove_all_hydrogens()
#
# Read mol2 file
#
L=Protool.ligand(P)
for mol2file in mol2files:
print "Added %s with tag 'LIGAND'" %mol2file
L.readmol2(mol2file,tag='LIGAND')
#
# Get the pdb lines
#
pdblines=P.writepdb('junk.pdb',nowrite=True)
#
# Pass the lines to FFF
#
import FFF.FFFcontrol
myFFF=FFF.FFFcontrol.FFF()
myFFF.parse_lines(pdblines)
#myFFF.soup_stat()
Model=FFF.FFFcontrol.model_class(myFFF,Rotamerlib,FFFaadef_dir)
#
# Store the wild type PDB file
#
if store_mutation_operations:
wt_lines=myFFF.make_pdblines('PDB')
#
import pKa.pKD_tools as pKD_tools
total_bump=0.0
for mutation in mutations:
resid=pKD_tools.get_resid_from_mut(mutation)
chainid=resid.split(':')[0]
resid=resid.split(':')[1]
#
# Get rid of the leading zeros
#
done=False
while not done:
if resid[0]=='0' and len(resid)>1:
resid=resid[1:]
else:
done=True
#
newres=pKD_tools.get_newrestyp_from_mut(mutation)
oldres=pKD_tools.get_oldrestyp_from_mut(mutation)
opttype=3 # Rotamer library
energies=Model.Mutate(chainid,resid,newres,opttype,max_overlap)
bump_score=energies[0]
Sum=energies[1]
Coulomb=energies[2]
#
total_bump=total_bump+bump_score
print 'Bump score: %5.2f, total bump: %5.2f' %(bump_score,total_bump)
if bump_score>max_overlap or total_bump>max_totalbump:
print 'Cannot model this set of mutations - too many bumps'
if return_score:
return False, total_bump
else:
return False
print 'Bump score for %s: %5.3f' %(mutation,bump_score)
print 'Total bump score for all mutations: %5.3f' %(total_bump)
class FFF_fix:
def __init__(self,FFF):
self.PI=FFF
return
#
# Create the instance
#
FFF_instance=FFF_fix(myFFF)
#
# Keep track of the changes that were made to the PDB file
#
if store_mutation_operations:
mut_lines=FFF_instance.PI.make_pdblines('PDB')
import Protool
WT=Protool.structureIO()
WT.parsepdb(wt_lines)
wt_atoms=sorted(WT.atoms.keys())
#
MUT=Protool.structureIO()
MUT.parsepdb(mut_lines)
#
mut_atoms=sorted(MUT.atoms.keys())
wt_count=0
mutcount=0
def coord_diff(atom1,atom2):
diff=0.0
for coord in ['X','Y','Z']:
diff=diff+abs(atom1[coord]-atom2[coord])
return diff
operations=[]
for atom in wt_atoms:
if not atom in mut_atoms:
operations.append(['delete',atom,WT.atoms[atom]])
elif coord_diff(WT.atoms[atom],MUT.atoms[atom])>0.1:
operations.append(['delete',atom,WT.atoms[atom]])
operations.append(['add',atom,MUT.atoms[atom]])
else:
pass
for atom in mut_atoms:
if not atom in wt_atoms:
operations.append(['add',atom,MUT.atoms[atom]])
#
# Store these in FFF_fix
#
FFF_instance.mutate_operations=operations[:]
#
# Return the info
#
if (return_score):
return FFF_instance,total_bump
return FFF_instance
