def make_confspace(cfs_file, data, cfs_dir=DEFAULT_CFS_DIR):
"""make_confspace
Generate conf spaces from input file
Takes as input a cfs_file that contains chain definitions, flexible
residues, and mutable residues.
Returns a dictionary containing forcefield parameters and OSPREY
confspace objects for:
protein
ligand
complex
"""
# Get the pdb code for this design
data["pdb"] = cfs_file[:4]
print("pdb: %s" % data["pdb"])
# Load the design conformation space information
data["cfs"] = os.path.join(cfs_dir, cfs_file)
confspace = imp.load_source('confspace', data["cfs"])
print("CFS File: %s" % data["cfs"])
# Get the sequences if they exist
try:
data["sequences"] = confspace.sequences
except AttributeError:
data["sequences"] = [None]
ffparams = osprey.ForcefieldParams()
mol = osprey.readPdb(confspace.mol)
template_library = osprey.TemplateLibrary(ffparams.forcefld)
# Make sure we don't have 3 strands (some cfs files do)
assert len(confspace.strand_defs) == 2
# Define the protein strand
protein = osprey.Strand(mol,
templateLib=template_library,
residues=confspace.strand_defs["strand0"])
for resi, res_allowed in confspace.strand_flex["strand0"].iteritems():
protein.flexibility[resi]\
.setLibraryRotamers(osprey.WILD_TYPE, *res_allowed)\
.setContinuous()\
.addWildTypeRotamers()
# Define the ligand strand
ligand = osprey.Strand(mol,
templateLib=template_library,
residues=confspace.strand_defs["strand1"])
for resi, res_allowed in confspace.strand_flex["strand1"].iteritems():
ligand.flexibility[resi]\
.setLibraryRotamers(osprey.WILD_TYPE,*res_allowed)\
.setContinuous()\
.addWildTypeRotamers()
# Build spaces
return {
'protein': osprey.ConfSpace(protein),
'ligand': osprey.ConfSpace(ligand),
'complex': osprey.ConfSpace([protein, ligand]),
'ffparams': ffparams
}
import osprey
osprey.start()
# choose a forcefield
ffparams = osprey.ForcefieldParams()
# read a PDB file for molecular info
mol = osprey.readPdb(
'../../test-resources/4npd.A_DomainA_noH_trim_his_clean.min.pdb')
# make sure all strands share the same template library
templateLib = osprey.TemplateLibrary(ffparams.forcefld)
# define the protein strand
protein = osprey.Strand(mol, templateLib=templateLib, residues=['A1', 'A37'])
protein.flexibility['A8'].setLibraryRotamers(
osprey.WILD_TYPE).addWildTypeRotamers().setContinuous()
# define the ligand strand
ligand = osprey.Strand(mol, templateLib=templateLib, residues=['A38', 'A58'])
ligand.flexibility['A41'].setLibraryRotamers(
osprey.WILD_TYPE).addWildTypeRotamers().setContinuous()
ligand.flexibility['A42'].setLibraryRotamers(
osprey.WILD_TYPE, 'THR', 'LYS').addWildTypeRotamers().setContinuous()
ligand.flexibility['A45'].setLibraryRotamers(
osprey.WILD_TYPE).addWildTypeRotamers().setContinuous()
ligand.flexibility['A46'].setLibraryRotamers(
osprey.WILD_TYPE).addWildTypeRotamers().setContinuous()
# make the conf space for the protein+ligand complex
import osprey osprey.start() # default template library contains templates, coords, entropies etc for natual amino acids defaultTemplateLib = osprey.TemplateLibrary() # define our custom templates customTemplates = """ Ignored comment 1 Ignored comment 2 ALANINE ALA INT 1 CORR OMIT DU BEG 0.00000 1 DUMM DU M 0 -1 -2 0.000 0.000 0.000 0.00000 2 DUMM DU M 1 0 -1 1.449 0.000 0.000 0.00000 3 DUMM DU M 2 1 0 1.522 111.100 0.000 0.00000 4 N N M 3 2 1 1.335 116.600 180.000 -0.41570 5 H H E 4 3 2 1.010 119.800 0.000 0.27190 6 CA CT M 4 3 2 1.449 121.900 180.000 0.03370 7 HA H1 E 6 4 3 1.090 109.500 300.000 0.08230 8 CB CT 3 6 4 3 1.525 111.100 60.000 -0.18250 9 HB1 HC E 8 6 4 1.090 109.500 60.000 0.06030 10 HB2 HC E 8 6 4 1.090 109.500 180.000 0.06030 11 HB3 HC E 8 6 4 1.090 109.500 300.000 0.06030 12 C C M 6 4 3 1.522 111.100 180.000 0.59730 13 O O E 12 6 4 1.229 120.500 0.000 -0.56790 IMPROPER -M CA N H
import osprey
osprey.start()
# choose a forcefield
ffparams = osprey.ForcefieldParams()
# read a PDB file for molecular info
mol = osprey.readPdb('2RL0.min.reduce.pdb')
# make sure all strands share the same template library (including wild-type rotamers)
templateLib = osprey.TemplateLibrary(ffparams.forcefld,
moleculesForWildTypeRotamers=[mol])
# define the protein strand
protein = osprey.Strand(mol,
templateLib=templateLib,
residues=['G648', 'G654'])
protein.flexibility['G649'].setLibraryRotamers(osprey.WILD_TYPE, 'TYR', 'ALA', 'VAL', 'ILE', 'LEU') \
.addWildTypeRotamers().setContinuous()
for res in ['G650', 'G651', 'G654']:
protein.flexibility[res].setLibraryRotamers(
osprey.WILD_TYPE).addWildTypeRotamers().setContinuous()
# define the ligand strand
ligand = osprey.Strand(mol, templateLib=templateLib, residues=['A155', 'A194'])
for res in ['A156', 'A172', 'A192', 'A193']:
ligand.flexibility['A156'].setLibraryRotamers(
osprey.WILD_TYPE).addWildTypeRotamers().setContinuous()
# make the conf space for the protein, ligand, and complex
proteinConfSpace = osprey.ConfSpace(protein)
osprey.start()
# what kind of hardware do we have?
parallelism = osprey.Parallelism(cpuCores=2)
# or use GPUs
gpuPrallelism = osprey.Parallelism(cpuCores=2, gpus=1, streamsPerGpu=1)
# choose a forcefield
ffparams = osprey.ForcefieldParams(osprey.Forcefield.AMBER)
ffparams.solvationForcefield = osprey.SolvationForcefield.EEF1 # this is the default
# or turn off solvation energy
#ffparams.solvationForcefield = None
# choose a template library
# (see templateLibrary.py for more detailed examples of custom template libraries)
templateLib = osprey.TemplateLibrary()
# load a molecule
mol = osprey.readPdb('1CC8.ss.pdb')
# define the protein strand
protein = osprey.Strand(mol, residues=['A2', 'A30'])
protein.flexibility['A2'].setLibraryRotamers('ALA', 'GLY')
protein.flexibility['A3'].setLibraryRotamers(osprey.WILD_TYPE, 'VAL',
'ARG').setContinuous(10)
protein.flexibility['A4'].setLibraryRotamers(
osprey.WILD_TYPE).addWildTypeRotamers()
# make the conf space
confSpace = osprey.ConfSpace(protein)
def loadd_confspaces(config,
xtal_rotamers=True,
continuous=False,
force_wt=True):
"""Loads OSPREY ConfSpace objects from a config dictionary.
OPTIONS:
xtal_rotamers: if true, add the rotamers from the input pdb
continuous: if true, set continuous rotamers
force_wt: if true, always add the wild-type amino acid
"""
ffparams = osprey.ForcefieldParams()
mol = osprey.readPdb(join(PDB, config["molecule"]))
template_library = osprey.TemplateLibrary(ffparams.forcefld)
# Make sure we don't have 3 strands (some cfs files do)
if len(config["strand_definitions"]) > 2:
exit()
# Define the protein strand
protein = osprey.Strand(mol,
templateLib=template_library,
residues=config["strand_definitions"]["strand0"])
for resi, res_allowed in config["strand_mutations"]["strand0"].items():
# Add the osprey.WILD_TYPE object to the allowed residues if desired
if force_wt:
res_allowed.append(osprey.WILD_TYPE)
# Set the flexibility
protein.flexibility[resi]\
.setLibraryRotamers(*res_allowed)
if xtal_rotamers:
protein.flexibility[resi].addWildTypeRotamers()
if continuous:
protein.flexibility[resi].setContinuous()
# Define the ligand strand
ligand = osprey.Strand(mol,
templateLib=template_library,
residues=config["strand_definitions"]["strand1"])
for resi, res_allowed in config["strand_mutations"]["strand1"].items():
# Add the osprey.WILD_TYPE object to the allowed residues if desired
if force_wt:
res_allowed.append(osprey.WILD_TYPE)
# Set the flexibility
ligand.flexibility[resi]\
.setLibraryRotamers(*res_allowed)
if xtal_rotamers:
ligand.flexibility[resi].addWildTypeRotamers()
if continuous:
ligand.flexibility[resi].setContinuous()
# Build spaces
return {
'protein': osprey.ConfSpace(protein),
'ligand': osprey.ConfSpace(ligand),
'complex': osprey.ConfSpace([protein, ligand]),
'ffparams': ffparams
}
