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()
# define a strand
strand = osprey.Strand('1CC8.ss.pdb')
strand.flexibility['A2'].setLibraryRotamers('ALA', 'GLY')
strand.flexibility['A3'].setLibraryRotamers(osprey.WILD_TYPE, 'VAL')
strand.flexibility['A4'].setLibraryRotamers(osprey.WILD_TYPE)
# make the conf space
confSpace = osprey.ConfSpace(strand)
# choose a forcefield
ffparams = osprey.ForcefieldParams()
# how should we compute energies of molecules?
ecalc = osprey.EnergyCalculator(confSpace, ffparams)
# how should we define energies of conformations?
confEcalc = osprey.ConfEnergyCalculator(confSpace, ecalc)
# compute the energy matrix
emat = osprey.EnergyMatrix(confEcalc)
# run DEE with just steric pruning
pmat = osprey.DEE(confSpace, emat, showProgress=True)
# or run DEE with Goldstein pruning
#i0 = 10.0 # kcal/mol
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
customizedTemplateLib = osprey.TemplateLibrary(
extraTemplates=[customTemplates],
extraTemplateCoords=[customTemplateCoords],
extraRotamers=[customRotamers])
# or read templates from files
# customizedTemplateLibFromFiles = osprey.TemplateLibrary(
# extraTemplates=['/path/to/templates/file']
# etc...
# )
# or completely replace default templates
# completelyCustomTemplateLib = osprey.TemplateLibrary(
# defaultTemplates=False,
# extraTemplates=['/path/to/all/templates'],
# etc...
# )
# load the molecule and make the strand using our custom template library
protein = osprey.Strand('1CC8.ss.pdb', templateLib=customizedTemplateLib)
# make the conf space
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()
confSpace = osprey.ConfSpace(protein)
# continue design with confSpace
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
templateLib = osprey.TemplateLibrary(ffparams.forcefld)
# 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()
protein.flexibility['G650'].setLibraryRotamers(
osprey.WILD_TYPE).addWildTypeRotamers().setContinuous()
protein.flexibility['G651'].setLibraryRotamers(
osprey.WILD_TYPE).addWildTypeRotamers().setContinuous()
protein.flexibility['G654'].setLibraryRotamers(
osprey.WILD_TYPE).addWildTypeRotamers().setContinuous()
# define the ligand strand
ligand = osprey.Strand(mol, templateLib=templateLib, residues=['A155', 'A194'])
ligand.flexibility['A156'].setLibraryRotamers(
osprey.WILD_TYPE).addWildTypeRotamers().setContinuous()
ligand.flexibility['A172'].setLibraryRotamers(
[
'LEU', 'ILE', 'ALA', 'VAL', 'PHE', 'TYR', 'MET', 'GLU',
'ASP', 'HID', 'ASN', 'GLN', 'GLY'
],
[
'GLU', 'ASP', 'PHE', 'TYR', 'ALA', 'VAL', 'ILE', 'LEU',
'HIE', 'HID', 'ASN', 'GLN', 'GLY'
]]
# make sure all strands share the same template library (including wild-type rotamers)
templateLib = osprey.TemplateLibrary(ffparams.forcefld,
moleculesForWildTypeRotamers=[mol])
# define the protein strand
ligand = osprey.Strand(mol,
templateLib=templateLib,
residues=[startResL, endResL])
for i in range(0, len(resNumsL)):
ligand.flexibility[resNumsL[i]].setLibraryRotamers(
*AATypeOptions[posL[i]]).addWildTypeRotamers().setContinuous()
# define the ligand strand
protein = osprey.Strand(mol,
templateLib=templateLib,
residues=[startResP, endResP])
for i in range(0, len(resNumsP)):
protein.flexibility[resNumsP[i]].setLibraryRotamers(
*AATypeOptions[posP[i]]).addWildTypeRotamers().setContinuous()
# make the conf space for the protein
confSpaceP = osprey.ConfSpace(protein)
osprey.start()
# let's go more faster
parallelism = osprey.Parallelism(cpuCores=2)
# if you have GPUs, designs can go much faster
#parallelism = osprey.Parallelism(cpuCores=2, gpus=1, streamsPerGpu=16)
# choose a forcefield
ffparams = osprey.ForcefieldParams()
# read a PDB file for molecular info
mol = osprey.readPdb('2RL0.min.reduce.pdb')
# define the conformation space
strand = osprey.Strand(mol, residues=['G648', 'G654'])
for resNum in ['G649', 'G650', 'G651']:
strand.flexibility[resNum]\
.setLibraryRotamers(osprey.WILD_TYPE)\
.addWildTypeRotamers()\
.setContinuous()
confSpace = osprey.MultiStateConfSpace([
# yeah, we didn't define any mutations,
# but SOFEA still needs one "mutable" state to define the sequence space
osprey.StateMutable('protein', osprey.ConfSpace(strand))
])
# we only care about the "wild-type" sequence in this case
seq = confSpace.seqSpace.makeWildTypeSequence()
# how should we compute energies of molecules?
# 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)
# how should molecule energies be calculated?
ecalc = osprey.EnergyCalculator(confSpace, ffparams, parallelism=parallelism)
# how could conformation energies be calculated?
confEcalc = osprey.ConfEnergyCalculator(confSpace, ecalc)
import osprey
# initializing osprey
osprey.start()
strand = osprey.Strand('2pt2FH.pdb')
# On strand we will define both the sequence and conformation space
# On every residue for which setLibraryRotamers is not called
# it will be modelled as fixed in space with its position found in the
# pdb file supplied.
# This is where Alanine scanning comes in.
# We can take the top K (tbd) most important residues and
# if they are close enough* to the ligand, i.e. we consider
# it to be on the surface of the protein, we can set it's possible
# mutations to negatively charged polar residues.
# negatively charged residues: ASP, GLUE
# polar uncharged: SER, THR, ASN, GLN, TYR, CYS
# Conversely, "deep" residues should only mutate to hydrophobic
# Fow now here are the residues in the "native pocket"
# For chain X residue number N, the residue is identified by 'XN'
#strand.flexibility['A54'].setLibraryRotamers(osprey.WILD_TYPE, 'ASP', 'GLU') # Wild type means the residue is free to be unchanged
# BUT will still have it's flexibility modelled
strand.flexibility['A145'].setLibraryRotamers(osprey.WILD_TYPE, 'ASP', 'GLU')
# Now the conf space is defined
confSpace = osprey.ConfSpace(strand)
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
}
import osprey
osprey.start()
mol = osprey.readPdb('1CC8.ss.pdb')
# define a strand
strand1 = osprey.Strand(mol, residues=['A2', 'A20'])
strand1.flexibility['A2'].setLibraryRotamers(
osprey.WILD_TYPE).addWildTypeRotamers()
strand1.flexibility['A3'].setLibraryRotamers(
osprey.WILD_TYPE).addWildTypeRotamers()
strand1.flexibility['A4'].setLibraryRotamers(
osprey.WILD_TYPE).addWildTypeRotamers()
# define another strand
strand2 = osprey.Strand(mol, residues=['A21', 'A40'])
strand2.flexibility['A21'].setLibraryRotamers(
osprey.WILD_TYPE).addWildTypeRotamers()
strand2.flexibility['A22'].setLibraryRotamers(
osprey.WILD_TYPE).addWildTypeRotamers()
strand2.flexibility['A23'].setLibraryRotamers(
osprey.WILD_TYPE).addWildTypeRotamers()
# make the conf space
confSpace = osprey.ConfSpace([strand1, strand2])
# choose a forcefield
ffparams = osprey.ForcefieldParams()
# how to compute the energy of a conformation?
osprey.start()
# choose a forcefield
ffparams = osprey.ForcefieldParams()
# read a PDB file for molecular info
mol = osprey.readPdb('2hnv_prepped.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
ligandStrand = osprey.Strand(mol,
templateLib=templateLib,
residues=['A7', 'A87'])
ligandStrand.flexibility['A25'].setLibraryRotamers(
osprey.WILD_TYPE, 'ASN', 'SER').setContinuous().addWildTypeRotamers()
ligandStrand.flexibility['A36'].setLibraryRotamers(
osprey.WILD_TYPE).setContinuous().addWildTypeRotamers()
# define the ligand strand
proteinStrand = osprey.Strand(mol,
templateLib=templateLib,
residues=['B7', 'B87'])
proteinStrand.flexibility['B81'].setLibraryRotamers(
osprey.WILD_TYPE).setContinuous().addWildTypeRotamers()
proteinStrand.flexibility['B72'].setLibraryRotamers(
osprey.WILD_TYPE).setContinuous().addWildTypeRotamers()
