def local_defaults(pdbfile,target_residues,recalc_intpka):
"""
# Set the parameters that are the same for all mutations
"""
import pKa.Design_pKa as Design_pKa
defaults=Design_pKa.get_defaults()
# PDB file
defaults['pdb'][0]=pdbfile
#
# pKa calculation parameters
#
defaults['pHstart'][0]=0.1
defaults['pHstop'][0]=12.0
defaults['pHstep'][0]=0.25
defaults['pKMCsteps'][0]=200000
#
# Design settings
#
# Target
#
target_residues=target_residues.split(',')
target_text=''
for target in target_residues:
target_text=target_text+target+'=0.0,' # Dummy pKa value
defaults['pKas'][0]=target_text[:-1]
#
# Method
#
defaults['MC'][0]=1
defaults['tabulated'][0]=1
defaults['MCsteps'][0]=0
#
# Be not-so-noisy
#
defaults['verbose'][0]=3
#
# Minimum distance between target and mutation
#
#defaults['min_target_dist'][0]=min_dist
#
# Do not save the solutions
#
defaults['save_solutions'][0]=None
#
#
defaults['recalc_intpka'][0]=recalc_intpka
defaults['recalc_intpka_dist'][0]=10.0
defaults['use_titration_curves'][0]=1
defaults['calc_dpka'][0]=1
defaults['generate_mutations'][0]=False
defaults['ligands'][0]=[]
defaults['allow_unknown_atoms'][0]=1
defaults['unknown_rad'][0]=0.0
return defaults
def local_defaults(pdbfile, target_residues, recalc_intpka):
"""
# Set the parameters that are the same for all mutations
"""
import pKa.Design_pKa as Design_pKa
defaults = Design_pKa.get_defaults()
# PDB file
defaults['pdb'][0] = pdbfile
#
# pKa calculation parameters
#
defaults['pHstart'][0] = 0.1
defaults['pHstop'][0] = 12.0
defaults['pHstep'][0] = 0.25
defaults['pKMCsteps'][0] = 200000
#
# Design settings
#
# Target
#
target_residues = target_residues.split(',')
target_text = ''
for target in target_residues:
target_text = target_text + target + '=0.0,' # Dummy pKa value
defaults['pKas'][0] = target_text[:-1]
#
# Method
#
defaults['MC'][0] = 1
defaults['tabulated'][0] = 1
defaults['MCsteps'][0] = 0
#
# Be not-so-noisy
#
defaults['verbose'][0] = 3
#
# Minimum distance between target and mutation
#
#defaults['min_target_dist'][0]=min_dist
#
# Do not save the solutions
#
defaults['save_solutions'][0] = None
#
#
defaults['recalc_intpka'][0] = recalc_intpka
defaults['recalc_intpka_dist'][0] = 10.0
defaults['use_titration_curves'][0] = 1
defaults['calc_dpka'][0] = 1
defaults['generate_mutations'][0] = False
defaults['ligands'][0] = []
defaults['allow_unknown_atoms'][0] = 1
defaults['unknown_rad'][0] = 0.0
return defaults
def local_defaults(pdbfile,target_residues,recalc_intpka):
"""
# Set the parameters that are the same for all mutations
"""
import pKa.Design_pKa as Design_pKa
defaults=Design_pKa.get_defaults()
# PDB file
defaults['pdb'][0]=pdbfile
#
# pKa calculation parameters
#
#defaults['pHstart'][0]=0.1
#defaults['pHstop'][0]=12.0
defaults['pHstep'][0]=0.01
defaults['pKMCsteps'][0]=200000
#
# Design settings
#
# Target
#
#target_residues=target_residues.split(',')
target_text=''
for target in target_residues:
target_text=target_text+target+'=0.0,' # Dummy pKa value
defaults['pKas'][0]=target_text[:-1]
#
# Method
#
defaults['dpKa_method']=['MC','junk']
defaults['tabulated'][0]=0
defaults['MCsteps'][0]=0
defaults['stability_mode']=[False,'junk']
defaults['PBEsolver']=['DelPhi','junk']
#
# Be not-so-noisy
#
defaults['verbose'][0]=5
#
# Minimum distance between target and mutation
#
#defaults['min_target_dist'][0]=min_dist
#
# Do not save the solutions
#
defaults['save_solutions'][0]=None
#
#
defaults['recalc_intpka'][0]=options.recalc_intpka
defaults['recalc_intpka_dist'][0]=options.recalc_intpka_dist
defaults['use_titration_curves'][0]=1
defaults['calc_dpka'][0]=1
defaults['generate_mutations'][0]=False
defaults['mutation_quality'][0]=0.5
return defaults
def designPKAOptions(self): '''Returns the options for the scan calculation in the format used by Design_pKa.run_opt Exceptions Raises an Exceptions.EnvironmentError if the pKa modules cannot be found''' try: import pKa.Design_pKa as Design_pKa except ImportError: raise Exceptions.ConfigurationError, "Cannot located Design_pKa module. Check correct path specified in configuration" #Get the default options defaults = Design_pKa.get_defaults() #Go through sections and set values for section in Configuration.scanSections: for option in self.configuration.options(section): #print option #print defaults[option] #Do some translating if self.configuration.get(section, option) == 'None': defaults[option][0] = None #print 'None conversion - Changed value of %s to %s' % (option, defaults[option]) elif type(defaults[option][0]) == float: defaults[option][0] = float(self.configuration.get(section, option)) #print 'Float conversion - Changed value of %s to %s' % (option, defaults[option]) elif type(defaults[option][0]) == int: defaults[option][0] = int(self.configuration.get(section, option)) #print 'Int conversion - Chaged value of %s to %s' % (option, defaults[option]) elif type(defaults[option][0]) == bool: confValue = self.configuration.get(section, option) #Accepts 1,0, True and False if confValue == 'True': confValue = True elif confValue == 'False': confValue = False else: confValue = bool(int(confValue)) defaults[option][0] = confValue #print 'Bool - Changed value of ', option, ' to ', defaults[option] else: defaults[option][0] = self.configuration.get(section, option) #print 'No conversion - Changed value of %s to %s' % (option, defaults[option]) return defaults
def main():
"""Load the PDB file, make all Ala mutations and calculate dpKa for the target residues"""
try:
import sys
pdbfile=sys.argv[1]
target_residues=sys.argv[2]
except:
print
print 'Usage: pKa_alascan.py <pdbfile> <target residues>'
print 'Example: pKa_alascan.py 2lzt.pdb :0035:GLU,:0052:ASP'
print 'This command will perform a full Alanine scan and report the effect of each mutation on the pKa values of Glu 35 and Asp 52'
print 'If ALL is supplied instead of a list of target residues, then dpKas will be calculated for all residues'
print
raise Exception,'Incorrect usage'
#
# Start the work
#
import Protool
P=Protool.structureIO()
P.readpdb(pdbfile)
residues=P.residues.keys()
residues.sort()
#
# All titgroups?
#
if target_residues=='ALL':
titgroups=P.get_titratable_groups()
import string
target_residues=string.join(titgroups,',')
#
# Start looping
#
results={}
import pickle, os
for residue in residues:
#
# Define result filename
#
resultfile=os.path.join(os.getcwd(),'alascan_%s.result' %residue)
if os.path.isfile(resultfile):
fd=open(resultfile)
results[residue]=pickle.load(fd)
fd.close()
else:
if P.resname(residue)=='ALA' or P.resname(residue)=='GLY' or not P.isaa(residue):
print 'Skipping',residue,P.resname(residue)
continue
print 'Calculating for residue',residue,P.resname(residue)
recalc_intpka=1
defaults=local_defaults(pdbfile,target_residues,recalc_intpka)
#
# Set the mutations
#
defaults['mutations'][0]='%s:%s:%s' %(residue,P.resname(residue),'ALA')
import pKa.Design_pKa as Design_pKa
#
# Calculate the dpKas
#
solutions,pKd_dict=Design_pKa.run_opt(defaults)
results[residue]=solutions.copy()
#
# Save this result
#
fd=open(resultfile,'w')
pickle.dump(results[residue],fd)
fd.close()
#
# Save all
#
name='%s.alascan.pickle' %pdbfile
fd=open(name,'w')
import pickle
pickle.dump(results,fd)
fd.close()
def main():
"""Load the PDB file, make all Ala mutations and calculate dpKa for the target residues"""
try:
import sys
pdbfile = sys.argv[1]
target_residues = sys.argv[2]
except:
print
print 'Usage: pKa_alascan.py <pdbfile> <target residues>'
print 'Example: pKa_alascan.py 2lzt.pdb :0035:GLU,:0052:ASP'
print 'This command will perform a full Alanine scan and report the effect of each mutation on the pKa values of Glu 35 and Asp 52'
print 'If ALL is supplied instead of a list of target residues, then dpKas will be calculated for all residues'
print
raise Exception, 'Incorrect usage'
#
# Start the work
#
import Protool
P = Protool.structureIO()
P.readpdb(pdbfile)
residues = P.residues.keys()
residues.sort()
#
# All titgroups?
#
if target_residues == 'ALL':
titgroups = P.get_titratable_groups()
import string
target_residues = string.join(titgroups, ',')
#
# Start looping
#
results = {}
import pickle, os
for residue in residues:
#
# Define result filename
#
resultfile = os.path.join(os.getcwd(), 'alascan_%s.result' % residue)
if os.path.isfile(resultfile):
fd = open(resultfile)
results[residue] = pickle.load(fd)
fd.close()
else:
if P.resname(residue) == 'ALA' or P.resname(
residue) == 'GLY' or not P.isaa(residue):
print 'Skipping', residue, P.resname(residue)
continue
print 'Calculating for residue', residue, P.resname(residue)
recalc_intpka = 1
defaults = local_defaults(pdbfile, target_residues, recalc_intpka)
#
# Set the mutations
#
defaults['mutations'][0] = '%s:%s:%s' % (residue,
P.resname(residue), 'ALA')
import pKa.Design_pKa as Design_pKa
#
# Calculate the dpKas
#
solutions, pKd_dict = Design_pKa.run_opt(defaults)
results[residue] = solutions.copy()
#
# Save this result
#
fd = open(resultfile, 'w')
pickle.dump(results[residue], fd)
fd.close()
#
# Save all
#
name = '%s.alascan.pickle' % pdbfile
fd = open(name, 'w')
import pickle
pickle.dump(results, fd)
fd.close()
def main(options,args):
"""Load the PDB file and the list of mutations"""
import sys
pdbfile=args[0]
target_residues=options.target_groups
#
# Load the PDB file
#
import Protool
P=Protool.structureIO()
P.readpdb(pdbfile)
residues=P.residues.keys()
residues.sort()
if not options.allmutations:
#
# Load the mutations
#
mutfile=args[1]
fd=open(mutfile)
mutlines=fd.readlines()
fd.close()
else:
mutlines=[]
aas=P.trueaminoacids.keys()
aas.sort()
count=1
for residue in residues:
for aa in aas:
if aa==P.resname(residue):
continue
mutlines.append('clone%d,%s:%s:%s' %(count,residue,P.resname(residue),aa))
count=count+1
print 'Created %d mutant proteins each containing 1 mutation' %len(mutlines)
#
# Make the resultdir
#
import os
resultdir=os.path.join(os.getcwd(),'pKa_mutscan_results')
if not os.path.isdir(resultdir):
os.mkdir(resultdir)
#
# which target residues
#
if target_residues==[] or target_residues==['ALL']:
target_residues=P.get_titratable_groups()
import string
target_residues=string.join(target_residues,',')
results={}
import pickle, os
for mline in mutlines:
import string
if mline[0]=='#' or mline[:2]=='//':
continue
#
line=string.strip(mline)
sp_line=line.split(',')
variant_name=sp_line[0]
mutation=sp_line[1]
print 'Variant: %s, mutations: %s' %(variant_name,mutation)
if mutation.find('insert')!=-1:
print 'Skipping insertions'
continue
#
# Define result filename
#
resultfile=os.path.join(resultdir,'mutscan_%s.result' %variant_name)
if os.path.isfile(resultfile):
fd=open(resultfile)
results[variant_name]=pickle.load(fd)
fd.close()
#print 'Already did',mutation
else:
recalc_intpka=1
defaults=local_defaults(pdbfile,target_residues,recalc_intpka)
#
# Set the mutations
#
import string
defaults['mutations'][0]=string.strip(mutation)
print 'Calculating for',mutation
import pKa.Design_pKa as Design_pKa
#
# Set other parameters
#
defaults['ion'][0]=options.ion
#
# Calculate the dpKas
#
#try:
solutions=Design_pKa.run_opt(defaults)
#except Exception,inst:
# if str(inst).find('Cannot model mutant')!=-1:
# solutions='Cannot model mutant'
# raise Exception('Cannot model mutant')
# elif str(inst).find('We cannot model insertions')!=-1:
# solutions='Skipping insertions'
# else:
# print inst
# raise Exception(str(inst))
print
print
print 'Results are ',solutions
results[variant_name]=solutions
#
# Save this result
#
print 'Saving',results[variant_name],'in',resultfile
import os
if len(os.path.split(resultfile)[1])>80:
continue
fd=open(resultfile,'w')
pickle.dump(results[variant_name],fd)
print '*********************'
fd.close()
#
# Save all
#
name=os.path.join(os.getcwd(),'%s.mutscan.pickle' %pdbfile)
fd=open(name,'w')
import pickle
pickle.dump(results,fd)
fd.close()
