def proteinPrepare(mol_in,
pH=7.0,
verbose=0,
returnDetails=False,
hydrophobicThickness=None,
holdSelection=None):
"""A system preparation wizard for HTMD.
Returns a Molecule object, where residues have been renamed to follow
internal conventions on protonation (below). Coordinates are changed to
optimize the H-bonding network. This should be roughly equivalent to mdweb and Maestro's
preparation wizard.
The following residue names are used in the returned molecule:
=== ===============================
ASH Neutral ASP
CYX SS-bonded CYS
CYM Negative CYS
GLH Neutral GLU
HIP Positive HIS
HID Neutral HIS, proton HD1 present
HIE Neutral HIS, proton HE2 present
LYN Neutral LYS
TYM Negative TYR
AR0 Neutral ARG
=== ===============================
========= ======= =========
Charge +1 Neutral Charge -1
========= ======= =========
- ASH ASP
- CYS CYM
- GLH GLU
HIP HID/HIE -
LYS LYN -
- TYR TYM
ARG AR0 -
========= ======= =========
A detailed table about the residues modified is returned (as a second return value) when
returnDetails is True (see PreparationData object).
If hydrophobicThickness is set to a positive value 2*h, a warning is produced for titratable residues
having -h<z<h and are buried in the protein by less than 75%. Note that the heuristic for the
detection of membrane-exposed residues is very crude; the "buried fraction" computation
(from propKa) is approximate; also, in the presence of cavities,
residues may be solvent-exposed independently from their z location.
Notes
-----
In case of problems, exclude water and other dummy atoms.
Features:
- assign protonation states via propKa
- flip residues to optimize H-bonding network
- debump collisions
- fill-in missing atoms, e.g. hydrogen atoms
Parameters
----------
mol_in : htmd.Molecule
the object to be optimized
pH : float
pH to decide titration
verbose : int
verbosity
returnDetails : bool
whether to return just the prepared Molecule (False, default) or a molecule *and* a ResidueInfo
object including computed properties
hydrophobicThickness : float
the thickness of the membrane in which the protein is embedded, or None if globular protein.
Used to provide a warning about membrane-exposed residues.
holdSelection : str
(Untested) Atom selection to be excluded from optimization.
Only the carbon-alpha atom will be considered for the corresponding residue.
Returns
-------
mol_out : Molecule
the molecule titrated and optimized. The molecule object contains an additional attribute,
resData : PreparationData
a table of residues with the corresponding protonation states, pKas, and other information
Examples
--------
>>> tryp = Molecule('3PTB')
>>> tryp_op, prepData = proteinPrepare(tryp, returnDetails=True)
>>> tryp_op.write('proteinpreparation-test-main-ph-7.pdb')
>>> prepData.data.to_excel("/tmp/tryp-report.xlsx")
>>> prepData # doctest: +NORMALIZE_WHITESPACE
PreparationData object about 290 residues.
Unparametrized residue names: CA, BEN
Please find the full info in the .data property, e.g.:
resname resid insertion chain pKa protonation flipped buried
0 ILE 16 A NaN ILE NaN NaN
1 VAL 17 A NaN VAL NaN NaN
2 GLY 18 A NaN GLY NaN NaN
3 GLY 19 A NaN GLY NaN NaN
4 TYR 20 A 9.590845 TYR NaN 14.642857
. . .
>>> x_HIE91_ND1 = tryp_op.get("coords","resid 91 and name ND1")
>>> x_SER93_H = tryp_op.get("coords","resid 93 and name H")
>>> len(x_SER93_H) == 3
True
>>> np.linalg.norm(x_HIE91_ND1-x_SER93_H) < 3
True
>>> tryp_op = proteinPrepare(tryp, pH=1.0)
>>> tryp_op.write('proteinpreparation-test-main-ph-1.pdb')
>>> tryp_op = proteinPrepare(tryp, pH=14.0)
>>> tryp_op.write('proteinpreparation-test-main-ph-14.pdb')
>>> mol = Molecule("1r1j")
>>> mo, prepData = proteinPrepare(mol, returnDetails=True)
>>> prepData.missedLigands
['NAG', 'ZN', 'OIR']
>>> his = prepData.data.resname == "HIS"
>>> prepData.data[his][["resid","insertion","chain","resname","protonation"]]
resid insertion chain resname protonation
160 214 A HIS HID
163 217 A HIS HID
383 437 A HIS HID
529 583 A HIS HID
533 587 A HIS HIP
583 637 A HIS HID
627 681 A HIS HID
657 711 A HIS HIP
679 733 A HIS HID
>>> mor = Molecule("4dkl")
>>> mor.filter("protein and noh")
>>> mor_opt, mor_data = proteinPrepare(mor, returnDetails=True,
... hydrophobicThickness=32.0)
>>> exposedRes = mor_data.data.membraneExposed
>>> mor_data.data[exposedRes].to_excel("/tmp/mor_exposed_residues.xlsx")
>>> im=Molecule("4bkj")
>>> imo,imd=proteinPrepare(im,returnDetails=True)
>>> imd.data.to_excel("/tmp/imatinib_report.xlsx")
See Also
--------
:class:`htmd.builder.PreparationData.PreparationData`
Notes
-----
Unsupported/To Do/To Check:
- ligands
- termini
- multiple chains
- nucleic acids
- coupled titrating residues
- Disulfide bridge detection (implemented but unused)
"""
oldLoggingLevel = logger.level
if verbose:
logger.setLevel(logging.DEBUG)
logger.debug("Starting.")
_warnIfContainsDUM(mol_in)
# We could transform the molecule into an internal object, but for
# now I prefer to rely on the strange internal parser to avoid
# hidden quirks.
tmpin = tempfile.NamedTemporaryFile(suffix=".pdb", mode="w+")
logger.debug("Temporary file is " + tmpin.name)
mol_in.write(tmpin.name) # Not sure this is good unix
pdblist, errlist = readPDB(tmpin)
if len(pdblist) == 0 and len(errlist) == 0:
raise Exception('Internal error in preparing input to pdb2pqr')
# An ugly hack to silence non-prefixed logging messages
for h in propka.lib.logger.handlers:
if h.formatter._fmt == '%(message)s':
propka.lib.logger.removeHandler(h)
propka_opts, dummy = propka.lib.loadOptions('--quiet')
propka_opts.verbosity = verbose
propka_opts.verbose = verbose # Will be removed in future propKas
# Note on naming. The behavior of PDB2PQR is controlled by two
# parameters, ff and ffout. My understanding is that the ff
# parameter sets which residues are SUPPORTED by the underlying
# FF, PLUS the charge and radii. The ffout parameter sets the
# naming scheme. Therefore, I want ff to be as general as
# possible, which turns out to be "parse". Then I pick a
# convenient ffout.
# Hold list (None -> None)
hlist = _selToHoldList(mol_in, holdSelection)
if hlist:
logger.warning("The holdSelection option is untested and deprecated. Please use reprepare()")
# Relying on defaults
pqr_res = runPDB2PQR(pdblist,
ph=pH, verbose=verbose,
ff="parse", ffout="amber",
ph_calc_method="propka31",
ph_calc_options=propka_opts,
holdList=hlist)
try:
header, pqr, missedLigands, pdb2pqr_protein, pdb2pqr_routines = \
pqr_res['header'], pqr_res['lines'], pqr_res['missedligands'], pqr_res['protein'], pqr_res['routines']
except:
logger.error("Problem calling pdb2pqr. Make sure you have htmd-pdb2pqr >= 2.1.2a9")
raise
tmpin.close()
# Diagnostics
for missedligand in missedLigands:
logger.warning("The following residue has not been optimized: " + missedligand)
mol_out, resData = _buildResAndMol(pdb2pqr_protein)
mol_out.box = mol_in.box
_fixupWaterNames(mol_out)
# Misc. info
resData.header = header
resData.pqr = pqr
# Return residue information
resData.pdb2pqr_protein = pdb2pqr_protein
resData.pdb2pqr_routines = pdb2pqr_routines
resData.missedLigands = missedLigands
# Store un-reprepared info
resData.data['default_protonation'] = resData.data['protonation']
resData._listNonStandardResidues()
resData._warnIfpKCloseTopH(pH)
resData.warnIfTerminiSuspect()
if hydrophobicThickness:
resData._setMembraneExposureAndWarn(hydrophobicThickness)
logger.debug("Returning.")
logger.setLevel(oldLoggingLevel)
if returnDetails:
return mol_out, resData
else:
return mol_out
def proteinPrepare(mol_in,
pH=7.0,
verbose=0,
returnDetails=False,
hydrophobicThickness=None,
holdSelection=None):
"""A system preparation wizard for HTMD.
Returns a Molecule object, where residues have been renamed to follow
internal conventions on protonation (below). Coordinates are changed to
optimize the H-bonding network. This should be roughly equivalent to mdweb and Maestro's
preparation wizard.
The following residue names are used in the returned molecule:
=== ===============================
ASH Neutral ASP
CYX SS-bonded CYS
CYM Negative CYS
GLH Neutral GLU
HIP Positive HIS
HID Neutral HIS, proton HD1 present
HIE Neutral HIS, proton HE2 present
LYN Neutral LYS
TYM Negative TYR
AR0 Neutral ARG
=== ===============================
========= ======= =========
Charge +1 Neutral Charge -1
========= ======= =========
- ASH ASP
- CYS CYM
- GLH GLU
HIP HID/HIE -
LYS LYN -
- TYR TYM
ARG AR0 -
========= ======= =========
A detailed table about the residues modified is returned (as a second return value) when
returnDetails is True (see PreparationData object).
If hydrophobicThickness is set to a positive value 2*h, a warning is produced for titratable residues
having -h<z<h and are buried in the protein by less than 75%. Note that the heuristic for the
detection of membrane-exposed residues is very crude; the "buried fraction" computation
(from propKa) is approximate; also, in the presence of cavities,
residues may be solvent-exposed independently from their z location.
Notes
-----
In case of problems, exclude water and other dummy atoms.
Features:
- assign protonation states via propKa
- flip residues to optimize H-bonding network
- debump collisions
- fill-in missing atoms, e.g. hydrogen atoms
Parameters
----------
mol_in : htmd.Molecule
the object to be optimized
pH : float
pH to decide titration
verbose : int
verbosity
returnDetails : bool
whether to return just the prepared Molecule (False, default) or a molecule *and* a ResidueInfo
object including computed properties
hydrophobicThickness : float
the thickness of the membrane in which the protein is embedded, or None if globular protein.
Used to provide a warning about membrane-exposed residues.
holdSelection : str
(Untested) Atom selection to be excluded from optimization.
Only the carbon-alpha atom will be considered for the corresponding residue.
Returns
-------
mol_out : Molecule
the molecule titrated and optimized. The molecule object contains an additional attribute,
resData : PreparationData
a table of residues with the corresponding protonation states, pKas, and other information
Examples
--------
>>> tryp = Molecule('3PTB')
>>> tryp_op, prepData = proteinPrepare(tryp, returnDetails=True)
>>> tryp_op.write('proteinpreparation-test-main-ph-7.pdb')
>>> prepData.data.to_excel("/tmp/tryp-report.xlsx")
>>> prepData # doctest: +NORMALIZE_WHITESPACE
PreparationData object about 290 residues.
Unparametrized residue names: CA, BEN
Please find the full info in the .data property, e.g.:
resname resid insertion chain pKa protonation flipped buried
0 ILE 16 A NaN ILE NaN NaN
1 VAL 17 A NaN VAL NaN NaN
2 GLY 18 A NaN GLY NaN NaN
3 GLY 19 A NaN GLY NaN NaN
4 TYR 20 A 9.590845 TYR NaN 14.642857
. . .
>>> x_HIE91_ND1 = tryp_op.get("coords","resid 91 and name ND1")
>>> x_SER93_H = tryp_op.get("coords","resid 93 and name H")
>>> len(x_SER93_H) == 3
True
>>> np.linalg.norm(x_HIE91_ND1-x_SER93_H) < 3
True
>>> tryp_op = proteinPrepare(tryp, pH=1.0)
>>> tryp_op.write('proteinpreparation-test-main-ph-1.pdb')
>>> tryp_op = proteinPrepare(tryp, pH=14.0)
>>> tryp_op.write('proteinpreparation-test-main-ph-14.pdb')
>>> mol = Molecule("1r1j")
>>> mo, prepData = proteinPrepare(mol, returnDetails=True)
>>> prepData.missedLigands
['NAG', 'ZN', 'OIR']
>>> his = prepData.data.resname == "HIS"
>>> prepData.data[his][["resid","insertion","chain","resname","protonation"]]
resid insertion chain resname protonation
160 214 A HIS HID
163 217 A HIS HID
383 437 A HIS HID
529 583 A HIS HID
533 587 A HIS HIP
583 637 A HIS HID
627 681 A HIS HID
657 711 A HIS HIP
679 733 A HIS HID
>>> mor = Molecule("4dkl")
>>> mor.filter("protein and noh")
>>> mor_opt, mor_data = proteinPrepare(mor, returnDetails=True,
... hydrophobicThickness=32.0)
>>> exposedRes = mor_data.data.membraneExposed
>>> mor_data.data[exposedRes].to_excel("/tmp/mor_exposed_residues.xlsx")
>>> im=Molecule("4bkj")
>>> imo,imd=proteinPrepare(im,returnDetails=True)
>>> imd.data.to_excel("/tmp/imatinib_report.xlsx")
See Also
--------
:class:`htmd.builder.PreparationData.PreparationData`
Notes
-----
Unsupported/To Do/To Check:
- ligands
- termini
- multiple chains
- nucleic acids
- coupled titrating residues
- Disulfide bridge detection (implemented but unused)
"""
oldLoggingLevel = logger.level
if verbose:
logger.setLevel(logging.DEBUG)
logger.debug("Starting.")
_warnIfContainsDUM(mol_in)
# We could transform the molecule into an internal object, but for
# now I prefer to rely on the strange internal parser to avoid
# hidden quirks.
tmpin = tempfile.NamedTemporaryFile(suffix=".pdb", mode="w+")
logger.debug("Temporary file is " + tmpin.name)
mol_in.write(tmpin.name) # Not sure this is good unix
pdblist, errlist = readPDB(tmpin)
if len(pdblist) == 0 and len(errlist) == 0:
raise Exception('Internal error in preparing input to pdb2pqr')
# An ugly hack to silence non-prefixed logging messages
for h in propka.lib.logger.handlers:
if h.formatter._fmt == '%(message)s':
propka.lib.logger.removeHandler(h)
propka_opts, dummy = propka.lib.loadOptions('--quiet')
propka_opts.verbosity = verbose
propka_opts.verbose = verbose # Will be removed in future propKas
# Note on naming. The behavior of PDB2PQR is controlled by two
# parameters, ff and ffout. My understanding is that the ff
# parameter sets which residues are SUPPORTED by the underlying
# FF, PLUS the charge and radii. The ffout parameter sets the
# naming scheme. Therefore, I want ff to be as general as
# possible, which turns out to be "parse". Then I pick a
# convenient ffout.
# Hold list (None -> None)
hlist = _selToHoldList(mol_in, holdSelection)
if hlist:
logger.warning(
"The holdSelection option is untested and deprecated. Please use reprepare()"
)
# Relying on defaults
pqr_res = runPDB2PQR(pdblist,
ph=pH,
verbose=verbose,
ff="parse",
ffout="amber",
ph_calc_method="propka31",
ph_calc_options=propka_opts,
holdList=hlist)
try:
header, pqr, missedLigands, pdb2pqr_protein, pdb2pqr_routines = \
pqr_res['header'], pqr_res['lines'], pqr_res['missedligands'], pqr_res['protein'], pqr_res['routines']
except:
logger.error(
"Problem calling pdb2pqr. Make sure you have htmd-pdb2pqr >= 2.1.2a9"
)
raise
tmpin.close()
# Diagnostics
for missedligand in missedLigands:
logger.warning("The following residue has not been optimized: " +
missedligand)
mol_out, resData = _buildResAndMol(pdb2pqr_protein)
mol_out.box = mol_in.box
_fixupWaterNames(mol_out)
# Misc. info
resData.header = header
resData.pqr = pqr
# Return residue information
resData.pdb2pqr_protein = pdb2pqr_protein
resData.pdb2pqr_routines = pdb2pqr_routines
resData.missedLigands = missedLigands
# Store un-reprepared info
resData.data['default_protonation'] = resData.data['protonation']
resData._listNonStandardResidues()
resData._warnIfpKCloseTopH(pH)
resData.warnIfTerminiSuspect()
if hydrophobicThickness:
resData._setMembraneExposureAndWarn(hydrophobicThickness)
logger.debug("Returning.")
logger.setLevel(oldLoggingLevel)
if returnDetails:
return mol_out, resData
else:
return mol_out
def prepareProtein(mol_in,
pH=7.0,
verbose=0,
returnDetails=False,
hydrophobicThickness=None,
holdSelection=None):
"""A system preparation wizard for HTMD.
Returns a Molecule object, where residues have been renamed to follow
internal conventions on protonation (below). Coordinates are changed to
optimize the H-bonding network. This should be roughly equivalent to mdweb and Maestro's
preparation wizard.
The following residue names are used in the returned molecule:
ASH Neutral ASP
CYX SS-bonded CYS
CYM Negative CYS
GLH Neutral GLU
HIP Positive HIS
HID Neutral HIS, proton HD1 present
HIE Neutral HIS, proton HE2 present
LYN Neutral LYS
TYM Negative TYR
AR0 Neutral ARG
If hydrophobicThickness is set to a positive value 2*h, a warning is produced for titratable residues
having -h<z<h and are buried in the protein by less than 75%. The list of such residues can be accessed setting
returnDetails to True. Note that the heuristic for the detection of membrane-exposed residues is very crude;
the "buried fraction" computation (from propka) is approximate; also, in the presence of cavities,
residues may be solvent-exposed independently from their z location.
Notes
-----
In case of problems, exclude water and other dummy atoms.
Features
--------
- assign protonation states via propKa
- flip residues to optimize H-bonding network
- debump collisions
- fill-in missing atoms, e.g. hydrogen atoms
Parameters
----------
mol_in : htmd.Molecule
the object to be optimized
pH : float
pH to decide titration
verbose : int
verbosity
returnDetails : bool
whether to return just the prepared Molecule (False, default) or a molecule *and* a ResidueInfo
object including computed properties
hydrophobicThickness : float
the thickness of the membrane in which the protein is embedded, or None if globular protein.
Used to provide a warning about membrane-exposed residues.
holdSelection : str
Atom selection to be excluded from optimization.
Only the carbon-alpha atom will be considered for the corresponding residue.
Returns
-------
mol_out : Molecule
the molecule titrated and optimized. The molecule object contains an additional attribute,
resData : ResidueData
a table of residues with the corresponding protonation states, pKas, and other information
Examples
--------
>>> tryp = Molecule('3PTB')
>>> tryp_op, prepData = prepareProtein(tryp, returnDetails=True)
>>> tryp_op.write('proteinpreparation-test-main-ph-7.pdb')
>>> prepData.data.to_excel("/tmp/tryp-report.xlsx")
>>> prepData
ResidueData object about 290 residues.
Unparametrized residue names: CA, BEN
Please find the full info in the .data property, e.g.:
resname resid insertion chain pKa protonation flipped buried
0 ILE 16 A NaN ILE NaN NaN
1 VAL 17 A NaN VAL NaN NaN
2 GLY 18 A NaN GLY NaN NaN
3 GLY 19 A NaN GLY NaN NaN
4 TYR 20 A 9.590845 TYR NaN 14.642857
. . .
>>> x_HIE91_ND1 = tryp_op.get("coords","resid 91 and name ND1")
>>> x_SER93_H = tryp_op.get("coords","resid 93 and name H")
>>> len(x_SER93_H) == 3
True
>>> np.linalg.norm(x_HIE91_ND1-x_SER93_H) < 3
True
>>> tryp_op = prepareProtein(tryp, pH=1.0)
>>> tryp_op.write('proteinpreparation-test-main-ph-1.pdb')
>>> tryp_op = prepareProtein(tryp, pH=14.0)
>>> tryp_op.write('proteinpreparation-test-main-ph-14.pdb')
>>> mol = Molecule("1r1j")
>>> mo, prepData = prepareProtein(mol, returnDetails=True)
>>> prepData.missedLigands
['NAG', 'ZN', 'OIR']
>>> his = prepData.data.resname == "HIS"
>>> prepData.data[his][["resid","insertion","chain","resname","protonation"]]
resid insertion chain resname protonation
160 214 A HIS HID
163 217 A HIS HID
383 437 A HIS HID
529 583 A HIS HID
533 587 A HIS HIP
583 637 A HIS HID
627 681 A HIS HID
657 711 A HIS HIP
679 733 A HIS HID
>>> mor = Molecule("4dkl")
>>> mor.filter("protein and noh")
>>> mor_opt, mor_data = prepareProtein(mor, returnDetails=True,
... hydrophobicThickness=32.0)
>>> exposedRes = mor_data.data.membraneExposed
>>> mor_data.data[exposedRes].to_excel("/tmp/mor_exposed_residues.xlsx")
>>> im=Molecule("4bkj")
>>> imo,imd=prepareProtein(im,returnDetails=True)
>>> imd.data.to_excel("/tmp/imatinib_report.xlsx")
See Also
--------
The ResidueData object.
Unsupported/To Do/To Check
--------------------------
- ligands
- termini
- force residues
- multiple chains
- nucleic acids
- reporting in machine-readable form
- coupled titrating residues
- Disulfide bridge detection (implemented but unused)
"""
oldLoggingLevel = logger.level
if verbose:
logger.setLevel(logging.DEBUG)
logger.debug("Starting.")
# We could transform the molecule into an internal object, but for
# now I prefer to rely on the strange internal parser to avoid
# hidden quirks.
tmpin = tempfile.NamedTemporaryFile(suffix=".pdb", mode="w+")
logger.debug("Temporary file is " + tmpin.name)
mol_in.write(tmpin.name) # Not sure this is sound unix
pdblist, errlist = readPDB(tmpin)
if len(pdblist) == 0 and len(errlist) == 0:
raise Exception('Internal error in preparing input to pdb2pqr')
# We could set additional options here
import propka.lib
# An ugly hack to silence non-prefixed logging messages
for h in propka.lib.logger.handlers:
if h.formatter._fmt == '%(message)s':
propka.lib.logger.removeHandler(h)
propka_opts, dummy = propka.lib.loadOptions('--quiet')
propka_opts.verbosity = verbose
propka_opts.verbose = verbose # Will be removed in future propKas
# Note on naming. The behavior of PDB2PQR is controlled by two
# parameters, ff and ffout. My understanding is that the ff
# parameter sets which residues are SUPPORTED by the underlying
# FF, PLUS the charge and radii. The ffout parameter sets the
# naming scheme. Therefore, I want ff to be as general as
# possible, which turns out to be "parse". Then I pick a
# convenient ffout.
# Hold list (None -> None)
hlist = _selToHoldList(mol_in, holdSelection)
# Relying on defaults
header, pqr, missedLigands, pdb2pqr_protein = runPDB2PQR(pdblist,
ph=pH, verbose=verbose,
ff="parse", ffout="amber",
ph_calc_method="propka31",
ph_calc_options=propka_opts,
holdList=hlist)
tmpin.close()
# Diagnostics
for missedligand in missedLigands:
logger.warning("The following residue has not been optimized: " + missedligand)
# Here I parse the returned protein object and recreate a Molecule,
# because I need to access the properties.
logger.debug("Building Molecule object.")
name = []
resid = []
chain = []
insertion = []
coords = []
resname = []
segids = []
elements = []
resData = ResidueData()
resData.header = header
resData.pqr = pqr
for residue in pdb2pqr_protein.residues:
# if 'ffname' in residue.__dict__:
if getattr(residue,'ffname',None):
curr_resname = residue.ffname
if len(curr_resname) >= 4:
curr_resname = curr_resname[-3:]
logger.debug("Residue %s has internal name %s, replacing with %s" %
(residue, residue.ffname, curr_resname))
else:
curr_resname = residue.name
resData._setProtonationState(residue, curr_resname)
#if 'patches' in residue.__dict__:
if getattr(residue, 'patches', None):
for patch in residue.patches:
resData._appendPatches(residue, patch)
if patch != "PEPTIDE":
logger.debug("Residue %s has patch %s set" % (residue, patch))
if getattr(residue, 'wasFlipped', 'UNDEF') != 'UNDEF':
resData._setFlipped(residue, residue.wasFlipped)
for atom in residue.atoms:
name.append(atom.name)
resid.append(residue.resSeq)
chain.append(residue.chainID)
insertion.append(residue.iCode)
coords.append([atom.x, atom.y, atom.z])
resname.append(curr_resname)
segids.append(atom.segID)
elements.append(atom.element)
mol_out = _fillMolecule(name, resname, chain, resid, insertion, coords, segids, elements)
_fixupWaterNames(mol_out)
# Return residue information
resData._importPKAs(pdb2pqr_protein.pka_protein)
resData.pdb2pqr_protein = pdb2pqr_protein
resData.missedLigands = missedLigands
resData._warnIfpKCloseTopH(pH)
if hydrophobicThickness:
resData._setMembraneExposureAndWarn(hydrophobicThickness)
logger.debug("Returning.")
logger.setLevel(oldLoggingLevel)
if returnDetails:
return mol_out, resData
else:
return mol_out
def proteinPrepare(mol_in,
pH=7.0,
verbose=0,
returnDetails=False,
hydrophobicThickness=None,
holdSelection=None):
"""A system preparation wizard for HTMD.
Returns a Molecule object, where residues have been renamed to follow
internal conventions on protonation (below). Coordinates are changed to
optimize the H-bonding network. This should be roughly equivalent to mdweb and Maestro's
preparation wizard.
The following residue names are used in the returned molecule:
ASH Neutral ASP
CYX SS-bonded CYS
CYM Negative CYS
GLH Neutral GLU
HIP Positive HIS
HID Neutral HIS, proton HD1 present
HIE Neutral HIS, proton HE2 present
LYN Neutral LYS
TYM Negative TYR
AR0 Neutral ARG
Charge +1 | Neutral | Charge -1
-------------|------------|----------
- | ASH | ASP
- | CYS | CYM
- | GLH | GLU
HIP | HID/HIE | -
LYS | LYN | -
- | TYR | TYM
ARG | AR0 | -
A detailed table about the residues modified is returned (as a second return value) when
returnDetails is True (see ResidueData object).
If hydrophobicThickness is set to a positive value 2*h, a warning is produced for titratable residues
having -h<z<h and are buried in the protein by less than 75%. Note that the heuristic for the
detection of membrane-exposed residues is very crude; the "buried fraction" computation
(from propKa) is approximate; also, in the presence of cavities,
residues may be solvent-exposed independently from their z location.
Notes
-----
In case of problems, exclude water and other dummy atoms.
Features
--------
- assign protonation states via propKa
- flip residues to optimize H-bonding network
- debump collisions
- fill-in missing atoms, e.g. hydrogen atoms
Parameters
----------
mol_in : htmd.Molecule
the object to be optimized
pH : float
pH to decide titration
verbose : int
verbosity
returnDetails : bool
whether to return just the prepared Molecule (False, default) or a molecule *and* a ResidueInfo
object including computed properties
hydrophobicThickness : float
the thickness of the membrane in which the protein is embedded, or None if globular protein.
Used to provide a warning about membrane-exposed residues.
holdSelection : str
Atom selection to be excluded from optimization.
Only the carbon-alpha atom will be considered for the corresponding residue.
Returns
-------
mol_out : Molecule
the molecule titrated and optimized. The molecule object contains an additional attribute,
resData : ResidueData
a table of residues with the corresponding protonation states, pKas, and other information
Examples
--------
>>> tryp = Molecule('3PTB')
>>> tryp_op, prepData = proteinPrepare(tryp, returnDetails=True)
>>> tryp_op.write('proteinpreparation-test-main-ph-7.pdb')
>>> prepData.data.to_excel("/tmp/tryp-report.xlsx")
>>> prepData
ResidueData object about 290 residues.
Unparametrized residue names: CA, BEN
Please find the full info in the .data property, e.g.:
resname resid insertion chain pKa protonation flipped buried
0 ILE 16 A NaN ILE NaN NaN
1 VAL 17 A NaN VAL NaN NaN
2 GLY 18 A NaN GLY NaN NaN
3 GLY 19 A NaN GLY NaN NaN
4 TYR 20 A 9.590845 TYR NaN 14.642857
. . .
>>> x_HIE91_ND1 = tryp_op.get("coords","resid 91 and name ND1")
>>> x_SER93_H = tryp_op.get("coords","resid 93 and name H")
>>> len(x_SER93_H) == 3
True
>>> np.linalg.norm(x_HIE91_ND1-x_SER93_H) < 3
True
>>> tryp_op = proteinPrepare(tryp, pH=1.0)
>>> tryp_op.write('proteinpreparation-test-main-ph-1.pdb')
>>> tryp_op = proteinPrepare(tryp, pH=14.0)
>>> tryp_op.write('proteinpreparation-test-main-ph-14.pdb')
>>> mol = Molecule("1r1j")
>>> mo, prepData = proteinPrepare(mol, returnDetails=True)
>>> prepData.missedLigands
['NAG', 'ZN', 'OIR']
>>> his = prepData.data.resname == "HIS"
>>> prepData.data[his][["resid","insertion","chain","resname","protonation"]]
resid insertion chain resname protonation
160 214 A HIS HID
163 217 A HIS HID
383 437 A HIS HID
529 583 A HIS HID
533 587 A HIS HIP
583 637 A HIS HID
627 681 A HIS HID
657 711 A HIS HIP
679 733 A HIS HID
>>> mor = Molecule("4dkl")
>>> mor.filter("protein and noh")
>>> mor_opt, mor_data = proteinPrepare(mor, returnDetails=True,
... hydrophobicThickness=32.0)
>>> exposedRes = mor_data.data.membraneExposed
>>> mor_data.data[exposedRes].to_excel("/tmp/mor_exposed_residues.xlsx")
>>> im=Molecule("4bkj")
>>> imo,imd=proteinPrepare(im,returnDetails=True)
>>> imd.data.to_excel("/tmp/imatinib_report.xlsx")
See Also
--------
The ResidueData object.
Unsupported/To Do/To Check
--------------------------
- ligands
- termini
- force residues
- multiple chains
- nucleic acids
- coupled titrating residues
- Disulfide bridge detection (implemented but unused)
"""
oldLoggingLevel = logger.level
if verbose:
logger.setLevel(logging.DEBUG)
logger.debug("Starting.")
_warnIfContainsDUM(mol_in)
# We could transform the molecule into an internal object, but for
# now I prefer to rely on the strange internal parser to avoid
# hidden quirks.
tmpin = tempfile.NamedTemporaryFile(suffix=".pdb", mode="w+")
logger.debug("Temporary file is " + tmpin.name)
mol_in.write(tmpin.name) # Not sure this is good unix
pdblist, errlist = readPDB(tmpin)
if len(pdblist) == 0 and len(errlist) == 0:
raise Exception('Internal error in preparing input to pdb2pqr')
# An ugly hack to silence non-prefixed logging messages
for h in propka.lib.logger.handlers:
if h.formatter._fmt == '%(message)s':
propka.lib.logger.removeHandler(h)
propka_opts, dummy = propka.lib.loadOptions('--quiet')
propka_opts.verbosity = verbose
propka_opts.verbose = verbose # Will be removed in future propKas
# Note on naming. The behavior of PDB2PQR is controlled by two
# parameters, ff and ffout. My understanding is that the ff
# parameter sets which residues are SUPPORTED by the underlying
# FF, PLUS the charge and radii. The ffout parameter sets the
# naming scheme. Therefore, I want ff to be as general as
# possible, which turns out to be "parse". Then I pick a
# convenient ffout.
# Hold list (None -> None)
hlist = _selToHoldList(mol_in, holdSelection)
# Relying on defaults
header, pqr, missedLigands, pdb2pqr_protein = runPDB2PQR(
pdblist,
ph=pH,
verbose=verbose,
ff="parse",
ffout="amber",
ph_calc_method="propka31",
ph_calc_options=propka_opts,
holdList=hlist)
tmpin.close()
# Diagnostics
for missedligand in missedLigands:
logger.warning("The following residue has not been optimized: " +
missedligand)
# Here I parse the returned protein object and recreate a Molecule,
# because I need to access the properties.
logger.debug("Building Molecule object.")
name = []
resid = []
chain = []
insertion = []
coords = []
resname = []
segid = []
element = []
occupancy = []
beta = []
record = []
charge = []
resData = ResidueData()
resData.header = header
resData.pqr = pqr
for residue in pdb2pqr_protein.residues:
# if 'ffname' in residue.__dict__:
if getattr(residue, 'ffname', None):
curr_resname = residue.ffname
if len(curr_resname) >= 4:
curr_resname = curr_resname[-3:]
logger.debug(
"Residue %s has internal name %s, replacing with %s" %
(residue, residue.ffname, curr_resname))
else:
curr_resname = residue.name
resData._setProtonationState(residue, curr_resname)
# if 'patches' in residue.__dict__:
if getattr(residue, 'patches', None):
for patch in residue.patches:
resData._appendPatches(residue, patch)
if patch != "PEPTIDE":
logger.debug("Residue %s has patch %s set" %
(residue, patch))
if getattr(residue, 'wasFlipped', 'UNDEF') != 'UNDEF':
resData._setFlipped(residue, residue.wasFlipped)
for atom in residue.atoms:
# Fixup element fields for added H (routines.addHydrogens)
elt = "H" if atom.added and atom.name.startswith(
"H") else atom.element
name.append(atom.name)
resid.append(residue.resSeq)
chain.append(residue.chainID)
insertion.append(residue.iCode)
coords.append([atom.x, atom.y, atom.z])
resname.append(curr_resname)
segid.append(atom.segID)
element.append(elt)
occupancy.append(atom.occupancy)
beta.append(atom.tempFactor)
charge.append(atom.charge)
record.append(atom.type)
mol_out = _fillMolecule(name, resname, chain, resid, insertion, coords,
segid, element, occupancy, beta, charge, record)
mol_out.box = mol_in.box
_fixupWaterNames(mol_out)
# Return residue information
resData._importPKAs(pdb2pqr_protein.pka_protein)
resData.pdb2pqr_protein = pdb2pqr_protein
resData.missedLigands = missedLigands
resData._listNonStandardResidues()
resData._warnIfpKCloseTopH(pH)
if hydrophobicThickness:
resData._setMembraneExposureAndWarn(hydrophobicThickness)
logger.debug("Returning.")
logger.setLevel(oldLoggingLevel)
if returnDetails:
return mol_out, resData
else:
return mol_out