def startpKa():
"""
Function for starting pKa script from the command line.
Returns
protein: The protein object as generated by PDB2PQR
routines: The routines object as generated by PDB2PQR
forcefield: The forcefield object as generated by PDB2PQR
"""
print
print 'PDB2PQR pKa calculations'
print
parser = optparse.OptionParser()
##
## set optparse options
##
parser.add_option(
'-v','--verbose',
dest='verbose',
action="store_true",
default=False,
)
parser.add_option(
'--pdie',
dest='pdie',
default=8,
type='int',
help='<protein dielectric constant>',
)
parser.add_option(
'--sdie',
dest='sdie',
default=80,
type='int',
help='<solvent dielectric constant>',
)
parser.add_option(
'--ff',
dest='ff',
type='choice',
default='parse',
choices=("amber","AMBER","charmm","CHARMM","parse","PARSE",),
help='<force field (amber, charmm, parse)>',
)
parser.add_option(
'--resume',
dest='resume',
action="store_true",
default=False,
help='resume run from saved state.',
)
parser.add_option(
'--ligand',
dest='ligand',
type='str',
help='<ligand in MOL2 format>',
)
parser.add_option(
'--maps',
dest='maps',
default=None,
type='int',
help='<1 for using provided 3D maps; 2 for genereting new maps>',
)
parser.add_option(
'--xdiel',
dest='xdiel',
default=None,
type='str',
help='<xdiel maps>',
)
parser.add_option(
'--ydiel',
dest='ydiel',
default=None,
type='str',
help='<ydiel maps>',
)
parser.add_option(
'--zdiel',
dest='zdiel',
default=None,
type='str',
help='<zdiel maps>',
)
parser.add_option(
'--kappa',
dest='kappa',
default=None,
type='str',
help='<ion-accessibility map>',
)
parser.add_option(
'--smooth',
dest='sd',
default=None,
type='float',
help='<st.dev [A] of Gaussian smooting of 3D maps at the boundary, bandthwith=3 st.dev>',
)
#
# Cut off energy for calculating non-charged-charged interaction energies
#
parser.add_option('--pairene',dest='pairene',type='float',default=1.0,
help='Cutoff energy in kT for calculating non charged-charged interaction energies. Default: %default')
#
# Options for doing partial calculations
#
parser.add_option('--res_energy',
dest='desolvation_res',
default=[],
action='append',
type='string',
help='Calculate desolvation energy and interaction energy for this residue in its default protonation state. Protonation states can be specified with the --protonation_state argument')
parser.add_option('--PS_file',dest='PS_file',default='',type='string',action='store',help='Set protonation states according to the pdb2pka protonation state file (option --PS_file)')
(options,args,) = parser.parse_args()
##
## parse optparse options
##
ff = options.ff.lower()
pdie = options.pdie
verbose = options.verbose
sdie = options.sdie
maps = options.maps
xdiel = options.xdiel
ydiel = options.ydiel
zdiel = options.zdiel
kappa = options.kappa
sd = options.sd
#
# Find the PDB file
#
if len(args) != 2:
parser.error("Usage: pka.py [options] <pdbfile> <output directory>\n")
input_path = args[0]
output_path = args[1]
ligand = None
if options.ligand is not None:
try:
ligand = open(options.ligand, 'rU')
except IOError:
print 'Unable to find ligand file %s! Skipping...' % options.ligand
#Set up the protien object
#In the standalone version of pdb2pka this is redundent but needed so we emulate the
#interface needed by pdb2pqr
pdbfile = getPDBFile(input_path)
pdblist, errlist = readPDB(pdbfile)
if len(errlist) != 0 and verbose:
print "Warning: %s is a non-standard PDB file.\n" %input_path
print errlist
#
# Read the definition file
#
myDefinition = Definition()
#
#
# Choose whether to include the ligand or not
#
# Add the ligand to the pdb2pqr arrays
#
if ligand is None:
myProtein = Protein(pdblist, myDefinition)
else:
from pdb2pka.ligandclean import ligff
myProtein, _, _ = ligff.initialize(myDefinition, ligand, pdblist, verbose)
#
# Call the pre_init function
#
return pre_init(protein=myProtein,
output_dir=output_path,
ff=ff,
verbose=verbose,
pdie=pdie,
sdie=sdie,
maps=maps,
xdiel=xdiel,
ydiel=ydiel,
zdiel=zdiel,
kappa=kappa,
sd=sd,
ligand=ligand),options
def startpKa():
"""
Function for starting pKa script from the command line.
Returns
protein: The protein object as generated by PDB2PQR
routines: The routines object as generated by PDB2PQR
forcefield: The forcefield object as generated by PDB2PQR
"""
print
print 'PDB2PQR pKa calculations'
print
parser = optparse.OptionParser()
##
## set optparse options
##
parser.add_option(
'-v',
'--verbose',
dest='verbose',
action="store_true",
default=False,
)
parser.add_option(
'--pdie',
dest='pdie',
default=8,
type='int',
help='<protein dielectric constant>',
)
parser.add_option(
'--sdie',
dest='sdie',
default=80,
type='int',
help='<solvent dielectric constant>',
)
parser.add_option(
'--ff',
dest='ff',
type='choice',
default='parse',
choices=(
"amber",
"AMBER",
"charmm",
"CHARMM",
"parse",
"PARSE",
),
help='<force field (amber, charmm, parse)>',
)
parser.add_option(
'--resume',
dest='resume',
action="store_true",
default=False,
help='resume run from saved state.',
)
parser.add_option(
'--ligand',
dest='ligand',
type='str',
help='<ligand in MOL2 format>',
)
parser.add_option(
'--maps',
dest='maps',
default=None,
type='int',
help='<1 for using provided 3D maps; 2 for genereting new maps>',
)
parser.add_option(
'--xdiel',
dest='xdiel',
default=None,
type='str',
help='<xdiel maps>',
)
parser.add_option(
'--ydiel',
dest='ydiel',
default=None,
type='str',
help='<ydiel maps>',
)
parser.add_option(
'--zdiel',
dest='zdiel',
default=None,
type='str',
help='<zdiel maps>',
)
parser.add_option(
'--kappa',
dest='kappa',
default=None,
type='str',
help='<ion-accessibility map>',
)
parser.add_option(
'--smooth',
dest='sd',
default=None,
type='float',
help=
'<st.dev [A] of Gaussian smooting of 3D maps at the boundary, bandthwith=3 st.dev>',
)
#
# Cut off energy for calculating non-charged-charged interaction energies
#
parser.add_option(
'--pairene',
dest='pairene',
type='float',
default=1.0,
help=
'Cutoff energy in kT for calculating non charged-charged interaction energies. Default: %default'
)
#
# Options for doing partial calculations
#
parser.add_option(
'--res_energy',
dest='desolvation_res',
default=[],
action='append',
type='string',
help=
'Calculate desolvation energy and interaction energy for this residue in its default protonation state. Protonation states can be specified with the --protonation_state argument'
)
parser.add_option(
'--PS_file',
dest='PS_file',
default='',
type='string',
action='store',
help=
'Set protonation states according to the pdb2pka protonation state file (option --PS_file)'
)
(
options,
args,
) = parser.parse_args()
##
## parse optparse options
##
ff = options.ff.lower()
pdie = options.pdie
verbose = options.verbose
sdie = options.sdie
maps = options.maps
xdiel = options.xdiel
ydiel = options.ydiel
zdiel = options.zdiel
kappa = options.kappa
sd = options.sd
#
# Find the PDB file
#
if len(args) != 2:
parser.error("Usage: pka.py [options] <pdbfile> <output directory>\n")
input_path = args[0]
output_path = args[1]
ligand = None
if options.ligand is not None:
try:
ligand = open(options.ligand, 'rU')
except IOError:
print 'Unable to find ligand file %s! Skipping...' % options.ligand
#Set up the protien object
#In the standalone version of pdb2pka this is redundent but needed so we emulate the
#interface needed by pdb2pqr
pdbfile = getPDBFile(input_path)
pdblist, errlist = readPDB(pdbfile)
if len(errlist) != 0 and verbose:
print "Warning: %s is a non-standard PDB file.\n" % input_path
print errlist
#
# Read the definition file
#
myDefinition = Definition()
#
#
# Choose whether to include the ligand or not
#
# Add the ligand to the pdb2pqr arrays
#
if ligand is None:
myProtein = Protein(pdblist, myDefinition)
else:
from pdb2pka.ligandclean import ligff
myProtein, _, _ = ligff.initialize(myDefinition, ligand, pdblist,
verbose)
#
# Call the pre_init function
#
return pre_init(protein=myProtein,
output_dir=output_path,
ff=ff,
verbose=verbose,
pdie=pdie,
sdie=sdie,
maps=maps,
xdiel=xdiel,
ydiel=ydiel,
zdiel=zdiel,
kappa=kappa,
sd=sd,
ligand=ligand), options
def pre_init(original_pdb_list=None,
output_dir=None,
ff=None,
verbose=False,
pdie=8.0,
sdie=80,
maps=None,
xdiel=None,
ydiel=None,
zdiel=None,
kappa=None,
sd=None,
ligand=None):
"""This function cleans the PDB and prepares the APBS input file
Prepares the output folder."""
#prepare the output directory
output_dir = os.path.abspath(output_dir)
try:
os.makedirs(output_dir)
except OSError:
if not os.path.isdir(output_dir):
raise ValueError('Target directory is a file! Aborting.')
workspace_dir = os.path.join(output_dir,'workspace')
try:
os.makedirs(workspace_dir)
except OSError:
if not os.path.isdir(output_dir):
raise ValueError('Target directory is a file! Aborting.')
#
# remove hydrogen atoms
#
working_pdb_filename = os.path.join(workspace_dir,'working.pdb')
pka_help.dump_protein_no_hydrogens(original_pdb_list, working_pdb_filename)
#
# Get the PDBfile
#
pdbfile = getPDBFile(working_pdb_filename)
pdblist, errlist = readPDB(pdbfile)
if verbose:
print "Beginning PDB2PKA...\n"
#
# Read the definition file
#
myDefinition = Definition()
ligand_titratable_groups=None
#
#
# Choose whether to include the ligand or not
#
# Add the ligand to the pdb2pqr arrays
#
Lig=None
if ligand is None:
myProtein = Protein(pdblist, myDefinition)
else:
from pdb2pka.ligandclean import ligff
myProtein, myDefinition, Lig = ligff.initialize(myDefinition, ligand, pdblist, verbose)
#
# =======================================================================
#
# We have identified the structural elements, now contiue with the setup
#
# Print something for some reason?
#
if verbose:
print "Created protein object -"
print "\tNumber of residues in protein: %s" % myProtein.numResidues()
print "\tNumber of atoms in protein : %s" % myProtein.numAtoms()
#
# Set up all other routines
#
myRoutines = Routines(myProtein, verbose) #myDefinition)
myRoutines.updateResidueTypes()
myRoutines.updateSSbridges()
myRoutines.updateBonds()
myRoutines.setTermini()
myRoutines.updateInternalBonds()
myRoutines.applyNameScheme(Forcefield(ff, myDefinition, None))
myRoutines.findMissingHeavy()
myRoutines.addHydrogens()
myRoutines.debumpProtein()
#myRoutines.randomizeWaters()
myProtein.reSerialize()
#
# Inject the information on hydrogen conformations in the HYDROGENS.DAT arrays
# We get this information from ligand_titratable_groups
#
from src.hydrogens import hydrogenRoutines
myRoutines.updateInternalBonds()
myRoutines.calculateDihedralAngles()
myhydRoutines = hydrogenRoutines(myRoutines)
#
# Here we should inject the info!!
#
myhydRoutines.setOptimizeableHydrogens()
myhydRoutines.initializeFullOptimization()
myhydRoutines.optimizeHydrogens()
myhydRoutines.cleanup()
myRoutines.setStates()
#
# Choose the correct forcefield
#
myForcefield = Forcefield(ff, myDefinition, None)
if Lig:
hitlist, misslist = myRoutines.applyForcefield(myForcefield)
#
# Can we get charges for the ligand?
#
templist=[]
ligsuccess=False
for residue in myProtein.getResidues():
if isinstance(residue, LIG):
templist = []
Lig.make_up2date(residue)
net_charge=0.0
print 'Ligand',residue
print 'Atom\tCharge\tRadius'
for atom in residue.getAtoms():
if atom.mol2charge:
atom.ffcharge=atom.mol2charge
else:
atom.ffcharge = Lig.ligand_props[atom.name]["charge"]
#
# Find the net charge
#
net_charge=net_charge+atom.ffcharge
#
# Assign radius
#
atom.radius = Lig.ligand_props[atom.name]["radius"]
print '%s\t%6.4f\t%6.4f' %(atom.name,atom.ffcharge,atom.radius)
if atom in misslist:
misslist.pop(misslist.index(atom))
templist.append(atom)
#
# Store the charge and radius in the atom instance for later use
# This really should be done in a nicer way, but this will do for now
#
atom.secret_radius=atom.radius
atom.secret_charge=atom.ffcharge
#
#
charge = residue.getCharge()
if abs(charge - round(charge)) > 0.01:
# Ligand parameterization failed
myProtein.residues.remove(residue)
raise Exception('Non-integer charge on ligand: %8.5f' %charge)
else:
ligsuccess = 1
# Mark these atoms as hits
hitlist = hitlist + templist
#
# Print the net charge
#
print 'Net charge for ligand %s is: %5.3f' %(residue.name,net_charge)
#
# Temporary fix; if ligand was successful, pull all ligands from misslist
# Not sure if this is needed at all here ...? (Jens wrote this)
#
if ligsuccess:
templist = misslist[:]
for atom in templist:
if isinstance(atom.residue, Amino) or isinstance(atom.residue, Nucleic):
continue
misslist.remove(atom)
if verbose:
print "Created protein object (after processing myRoutines) -"
print "\tNumber of residues in protein: %s" % myProtein.numResidues()
print "\tNumber of atoms in protein : %s" % myProtein.numAtoms()
#
# Create the APBS input file
#
import src.psize
size=src.psize.Psize()
method=""
async=0
split=0
igen = inputgen_pKa.inputGen(working_pdb_filename)
#
# For convenience
#
igen.pdie = pdie
print 'Setting protein dielectric constant to ',igen.pdie
igen.sdie=sdie
igen.maps=maps
if maps==1:
print "Using dielectric and mobile ion-accessibility function maps in PBE"
if xdiel:
igen.xdiel = xdiel
else:
raise PDB2PKAError('X dielectric map is missing')
if ydiel:
igen.ydiel = ydiel
else:
raise PDB2PKAError("Y dielectric map is missing\n")
if zdiel:
igen.zdiel = zdiel
else:
raise PDB2PKAError("Z dielectric map is missing\n")
print 'Setting dielectric function maps: %s, %s, %s'%(igen.xdiel,igen.ydiel,igen.zdiel)
if kappa:
igen.kappa = kappa
else:
raise PDB2PKAError("Mobile ion-accessibility map is missing\n")
print 'Setting mobile ion-accessibility function map to: ',igen.kappa
if sd:
xdiel_smooth, ydiel_smooth, zdiel_smooth = smooth(xdiel,ydiel,zdiel)
igen.xdiel = xdiel_smooth
igen.ydiel = ydiel_smooth
igen.zdiel = zdiel_smooth
#
# Return all we need
#
return output_dir, myProtein, myRoutines, myForcefield,igen, ligand_titratable_groups, maps, sd
def pre_init(original_pdb_list=None,
output_dir=None,
ff=None,
verbose=False,
pdie=8.0,
sdie=80,
maps=None,
xdiel=None,
ydiel=None,
zdiel=None,
kappa=None,
sd=None,
ligand=None):
"""This function cleans the PDB and prepares the APBS input file
Prepares the output folder."""
#prepare the output directory
output_dir = os.path.abspath(output_dir)
try:
os.makedirs(output_dir)
except OSError:
if not os.path.isdir(output_dir):
raise ValueError('Target directory is a file! Aborting.')
workspace_dir = os.path.join(output_dir, 'workspace')
try:
os.makedirs(workspace_dir)
except OSError:
if not os.path.isdir(output_dir):
raise ValueError('Target directory is a file! Aborting.')
#
# remove hydrogen atoms
#
working_pdb_filename = os.path.join(workspace_dir, 'working.pdb')
pka_help.dump_protein_no_hydrogens(original_pdb_list, working_pdb_filename)
#
# Get the PDBfile
#
pdbfile = getPDBFile(working_pdb_filename)
pdblist, errlist = readPDB(pdbfile)
if verbose:
print "Beginning PDB2PKA...\n"
#
# Read the definition file
#
myDefinition = Definition()
ligand_titratable_groups = None
#
#
# Choose whether to include the ligand or not
#
# Add the ligand to the pdb2pqr arrays
#
Lig = None
if ligand is None:
myProtein = Protein(pdblist, myDefinition)
else:
from pdb2pka.ligandclean import ligff
myProtein, myDefinition, Lig = ligff.initialize(
myDefinition, ligand, pdblist, verbose)
#
# =======================================================================
#
# We have identified the structural elements, now contiue with the setup
#
# Print something for some reason?
#
if verbose:
print "Created protein object -"
print "\tNumber of residues in protein: %s" % myProtein.numResidues()
print "\tNumber of atoms in protein : %s" % myProtein.numAtoms()
#
# Set up all other routines
#
myRoutines = Routines(myProtein, verbose) #myDefinition)
myRoutines.updateResidueTypes()
myRoutines.updateSSbridges()
myRoutines.updateBonds()
myRoutines.setTermini()
myRoutines.updateInternalBonds()
myRoutines.applyNameScheme(Forcefield(ff, myDefinition, None))
myRoutines.findMissingHeavy()
myRoutines.addHydrogens()
myRoutines.debumpProtein()
#myRoutines.randomizeWaters()
myProtein.reSerialize()
#
# Inject the information on hydrogen conformations in the HYDROGENS.DAT arrays
# We get this information from ligand_titratable_groups
#
from src.hydrogens import hydrogenRoutines
myRoutines.updateInternalBonds()
myRoutines.calculateDihedralAngles()
myhydRoutines = hydrogenRoutines(myRoutines)
#
# Here we should inject the info!!
#
myhydRoutines.setOptimizeableHydrogens()
myhydRoutines.initializeFullOptimization()
myhydRoutines.optimizeHydrogens()
myhydRoutines.cleanup()
myRoutines.setStates()
#
# Choose the correct forcefield
#
myForcefield = Forcefield(ff, myDefinition, None)
if Lig:
hitlist, misslist = myRoutines.applyForcefield(myForcefield)
#
# Can we get charges for the ligand?
#
templist = []
ligsuccess = False
for residue in myProtein.getResidues():
if isinstance(residue, LIG):
templist = []
Lig.make_up2date(residue)
net_charge = 0.0
print 'Ligand', residue
print 'Atom\tCharge\tRadius'
for atom in residue.getAtoms():
if atom.mol2charge:
atom.ffcharge = atom.mol2charge
else:
atom.ffcharge = Lig.ligand_props[atom.name]["charge"]
#
# Find the net charge
#
net_charge = net_charge + atom.ffcharge
#
# Assign radius
#
atom.radius = Lig.ligand_props[atom.name]["radius"]
print '%s\t%6.4f\t%6.4f' % (atom.name, atom.ffcharge,
atom.radius)
if atom in misslist:
misslist.pop(misslist.index(atom))
templist.append(atom)
#
# Store the charge and radius in the atom instance for later use
# This really should be done in a nicer way, but this will do for now
#
atom.secret_radius = atom.radius
atom.secret_charge = atom.ffcharge
#
#
charge = residue.getCharge()
if abs(charge - round(charge)) > 0.01:
# Ligand parameterization failed
myProtein.residues.remove(residue)
raise Exception('Non-integer charge on ligand: %8.5f' %
charge)
else:
ligsuccess = 1
# Mark these atoms as hits
hitlist = hitlist + templist
#
# Print the net charge
#
print 'Net charge for ligand %s is: %5.3f' % (residue.name,
net_charge)
#
# Temporary fix; if ligand was successful, pull all ligands from misslist
# Not sure if this is needed at all here ...? (Jens wrote this)
#
if ligsuccess:
templist = misslist[:]
for atom in templist:
if isinstance(atom.residue, Amino) or isinstance(
atom.residue, Nucleic):
continue
misslist.remove(atom)
if verbose:
print "Created protein object (after processing myRoutines) -"
print "\tNumber of residues in protein: %s" % myProtein.numResidues()
print "\tNumber of atoms in protein : %s" % myProtein.numAtoms()
#
# Create the APBS input file
#
import src.psize
size = src.psize.Psize()
method = ""
split = 0
igen = inputgen_pKa.inputGen(working_pdb_filename)
#
# For convenience
#
igen.pdie = pdie
print 'Setting protein dielectric constant to ', igen.pdie
igen.sdie = sdie
igen.maps = maps
if maps == 1:
print "Using dielectric and mobile ion-accessibility function maps in PBE"
if xdiel:
igen.xdiel = xdiel
else:
raise PDB2PKAError('X dielectric map is missing')
if ydiel:
igen.ydiel = ydiel
else:
raise PDB2PKAError("Y dielectric map is missing\n")
if zdiel:
igen.zdiel = zdiel
else:
raise PDB2PKAError("Z dielectric map is missing\n")
print 'Setting dielectric function maps: %s, %s, %s' % (
igen.xdiel, igen.ydiel, igen.zdiel)
if kappa:
igen.kappa = kappa
else:
raise PDB2PKAError("Mobile ion-accessibility map is missing\n")
print 'Setting mobile ion-accessibility function map to: ', igen.kappa
if sd:
xdiel_smooth, ydiel_smooth, zdiel_smooth = smooth(
xdiel, ydiel, zdiel)
igen.xdiel = xdiel_smooth
igen.ydiel = ydiel_smooth
igen.zdiel = zdiel_smooth
#
# Return all we need
#
return output_dir, myProtein, myRoutines, myForcefield, igen, ligand_titratable_groups, maps, sd