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#!/usr/bin/python3
#
# * This library is free software; you can redistribute it and/or
# * modify it under the terms of the GNU Lesser General Public
# * License as published by the Free Software Foundation; either
# * version 2.1 of the License, or (at your option) any later version.
# *
# * This library is distributed in the hope that it will be useful,
# * but WITHOUT ANY WARRANTY; without even the implied warranty of
# * MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU
# * Lesser General Public License for more details.
#
#propka3.0, revision 182 2011-08-09
#-------------------------------------------------------------------------------------------------------
#-- --
#-- PROPKA: A PROTEIN PKA PREDICTOR --
#-- --
#-- VERSION 3.0, 01/01/2011, COPENHAGEN --
#-- BY MATS H.M. OLSSON AND CHRESTEN R. SONDERGARD --
#-- --
#-------------------------------------------------------------------------------------------------------
#
#
#-------------------------------------------------------------------------------------------------------
# References:
#
# Very Fast Empirical Prediction and Rationalization of Protein pKa Values
# Hui Li, Andrew D. Robertson and Jan H. Jensen
# PROTEINS: Structure, Function, and Bioinformatics 61:704-721 (2005)
#
# Very Fast Prediction and Rationalization of pKa Values for Protein-Ligand Complexes
# Delphine C. Bas, David M. Rogers and Jan H. Jensen
# PROTEINS: Structure, Function, and Bioinformatics 73:765-783 (2008)
#
# PROPKA3: Consistent Treatment of Internal and Surface Residues in Empirical pKa predictions
# Mats H.M. Olsson, Chresten R. Sondergard, Michal Rostkowski, and Jan H. Jensen
# Journal of Chemical Theory and Computation, 7, 525-537 (2011)
#-------------------------------------------------------------------------------------------------------
import sys, pdb, protonate, lib, bonds
from .vector_algebra import *
pka_print = lib.pka_print
all_sybyl_types = [
'C.3', # carbon sp3
'H', # hydrogen
'C.2', # carbon sp2
'H.spc', # hydrogen in Single Point Charge (SPC) water model
'C.1', # carbon sp
'H.t3p', # hydrogen in Transferable intermolecular Potential (TIP3P) water model
'C.ar', # carbon aromatic
'LP', # lone pair
'C.cat', # carbocation (C+) used only in a guadinium group
'Du', # dummy atom
'N.3', # nitrogen sp3
'Du.C', # dummy carbon
'N.2', # nitrogen sp2
'Any', # any atom
'N.1', # nitrogen sp
'Hal', # halogen
'N.ar', # nitrogen aromatic
'Het', # heteroatom = N, O, S, P
'N.am', # nitrogen amide
'Hev', # heavy atom (non hydrogen)
'N.pl3', # nitrogen trigonal planar
'Li', # lithium
'N.4', # nitrogen sp3 positively charged
'Na', # sodium
'O.3', # oxygen sp3
'Mg', # magnesium
'O.2', # oxygen sp2
'Al', # aluminum
'O.co2', # oxygen in carboxylate and phosphate groups
'Si', # silicon
'O.spc', # oxygen in Single Point Charge (SPC) water model
'K', # potassium
'O.t3p', # oxygen in Transferable Intermolecular Potential (TIP3P) water model
'Ca', # calcium
'S.3', # sulfur sp3
'Cr.th', # chromium (tetrahedral)
'S.2', # sulfur sp2
'Cr.oh', # chromium (octahedral)
'S.O', # sulfoxide sulfur
'Mn', # manganese
'S.O2', # sulfone sulfur
'Fe', # iron
'P.3', # phosphorous sp3
'Co.oh', # cobalt (octahedral)
'F', # fluorine
'Cu', # copper
'Cl', # chlorine
'Zn', # zinc
'Br', # bromine
'Se', # selenium
'I', # iodine
'Mo', # molybdenum
'Sn'] # tin
#propka_input_types = ['1P','1N','2P','2N']
#for type in all_sybyl_types:
# temp = type.replace('.','')
# if len(temp)>3:
# temp = temp[0:3]
# propka_input_types.append(temp)
#
#for t in propka_input_types:
# print (t)
propka_input_types = [
'1P',
'1N',
'2P',
'2N',
'C3',
'H',
'C2',
'Hsp',
'C1',
'Ht3',
'Car',
'LP',
'Cca',
'Du',
'N3',
'DuC',
'N2',
'Any',
'N1',
'Hal',
'Nar',
'Het',
'Nam',
'Hev',
'Npl',
'Li',
'N4',
'Na',
'O3',
'Mg',
'O2',
'Al',
'Oco',
'Si',
'Osp',
'K',
'Ot3',
'Ca',
'S3',
'Crt',
'S2',
'Cro',
'SO',
'Mn',
'SO2',
'Fe',
'P3',
'Coo',
'F',
'Cu',
'Cl',
'Zn',
'Br',
'Se',
'I',
'Mo',
'Sn']
ions = ['CA','NA']
max_C_double_bond = 1.3
max_C_triple_bond = 1.2
max_C_double_bond_squared = max_C_double_bond*max_C_double_bond
max_C_triple_bond_squared = max_C_triple_bond*max_C_triple_bond
class ligand:
def __init__(self, atoms):
self.atoms = atoms
for atom in self.atoms:
atom.residue = self
#self.remove_ions()
self.configuration_keys = list(atoms[0].configurations.keys())
# create ligand residue objects
self.ligand_residues = []
self.split_into_residues()
return
def __str__(self):
res = '----Ligand----\n'
for atom in self.atoms:
res += '%s\n'%atom
res+='--------------'
return res
def split_into_residues(self):
residue = []
if len(self.atoms)>0:
current_residue_number = self.atoms[0].resNumb
for atom in self.atoms:
if atom.resNumb != current_residue_number:
self.ligand_residues.append(ligand_residue(residue))
residue = []
current_residue_number = atom.resNumb
residue.append(atom)
# remember to include the last ligand residue
self.ligand_residues.append(ligand_residue(residue))
return
def remove_ions(self):
self.atoms = [atom for atom in self.atoms if atom.get_element() not in ions]
return
def writePDB(self, pdbname):
pka_print("writing pdbfile %s" % (pdbname))
file = open(pdbname, 'w')
configurations = lib.get_sorted_configurations(self.configuration_keys)
if len(configurations)==1:
self.write_atoms(file)
else:
for configuration in configurations:
self.setConfiguration(configuration)
file.write('MODEL%9d\n'%int(configuration[1]))
self.write_atoms(file)
file.write('ENDMDL\n')
file.close()
return
def write_atoms(self,file):
atom_number=1
for atom in my_ligand.atoms:
atom.writePDB(file,atom_number)
atom_number+=1
return
def assign_atom_names(self):
"""
Assigns sybyl names to ligand atoms based on elements and coordinates
copied from propka/ligand.py
modified:
P -> P3
O.co2+ - > O.co2
"""
# find bonding atoms
self.my_bond_maker = bonds.bondmaker()
self.my_bond_maker.find_bonds_for_atoms(self.atoms)
for atom in self.atoms:
# check if we already have assigned a name to this atom
if hasattr(atom, 'sybyl_assigned'):
print((atom.resName, atom.numb, atom.name, 'alreadyassigned'))
continue
# find some properties of the atom
ring_atoms = self.is_ring_member(atom)
aromatic = self.is_aromatic_ring(ring_atoms)
planar = self.is_planar(atom)
bonded_elements = {}
for i in range(len(atom.bonded_atoms)):
bonded_elements[i] = atom.bonded_atoms[i].get_element()
# Aromatic carbon/nitrogen
if aromatic:
#print "--- if aromatic",atom.resName, atom.numb, atom.name, atom.get_element()
#for ra in ring_atoms:
# if ra.get_element() in ['C', 'N']:
# self.set_type(ra, ra.get_element() + '.ar')
#continue
'''SH: In the original version, if a ring is planar (eg., 4FXF_D_FBP_606)
but contains other atoms than C or N the loop breaks without assigning these atoms
'''
if atom.get_element() in ['C', 'N']:
self.set_type(atom, atom.get_element() + '.ar')
continue
# check for amide
if atom.get_element() in ['O', 'N']:
amide = 0
for b in atom.bonded_atoms:
if b.element == 'C':
for bb in b.bonded_atoms:
if (bb.get_element() == 'N' and atom.get_element() == 'O'):
self.set_type(bb, 'N.am')
self.set_type(b, 'C.2')
self.set_type(atom, 'O.2')
amide = 1
if (bb.get_element() == 'O' and atom.get_element() == 'N'):
self.set_type(atom, 'N.am')
self.set_type(b, 'C.2')
self.set_type(bb, 'O.2')
amide = 1
if amide == 1:
continue
if atom.get_element() == 'C':
# check for amide
if 'O' in list(bonded_elements.values()) and 'N' in list(bonded_elements.values()):
self.set_type(atom, 'C.2')
for b in atom.bonded_atoms:
if b.get_element() == 'N':
self.set_type(b, 'N.am')
if b.get_element() == 'O':
self.set_type(b, 'O.2')
continue
# check for carboxyl
if len(atom.bonded_atoms) == 3 and list(bonded_elements.values()).count('O') == 2:
i1 = list(bonded_elements.values()).index('O')
i2 = list(bonded_elements.values()).index('O', i1 + 1)
if len(atom.bonded_atoms[i1].bonded_atoms) == 1 and len(atom.bonded_atoms[i2].bonded_atoms) == 1:
#self.set_type(atom.bonded_atoms[i1], 'O.co2+')
self.set_type(atom.bonded_atoms[i1], 'O.co2') #SH: problems in 1a3w
self.set_type(atom.bonded_atoms[i2], 'O.co2')
self.set_type(atom, 'C.2')
continue
# sp carbon
if len(atom.bonded_atoms) <= 2:
for b in atom.bonded_atoms:
if self.my_bond_maker.squared_distance(atom, b) < max_C_triple_bond_squared:
self.set_type(atom, 'C.1')
self.set_type(b, b.get_element() + '.1')
if hasattr(atom, 'sybyl_assigned'):
continue
# sp2 carbon
if planar:
self.set_type(atom, 'C.2')
# check for N.pl3
for b in atom.bonded_atoms:
if b.get_element() == 'N':
if len(b.bonded_atoms) < 3 or self.is_planar(b):
self.set_type(b, 'N.pl3')
continue
# sp3 carbon
self.set_type(atom, 'C.3')
continue
# Nitrogen
if atom.get_element() == 'N':
# check for planar N
if len(atom.bonded_atoms) == 1:
if self.is_planar(atom.bonded_atoms[0]):
self.set_type(atom, 'N.pl3')
continue
if planar:
self.set_type(atom, 'N.pl3')
continue
self.set_type(atom, 'N.3')
continue
# Oxygen
if atom.get_element() == 'O':
self.set_type(atom, 'O.3')
# check for X=O
if len(atom.bonded_atoms) == 1:
if self.my_bond_maker.squared_distance(atom, atom.bonded_atoms[0]) < max_C_double_bond_squared:
self.set_type(atom, 'O.2')
if atom.bonded_atoms[0].get_element() == 'C':
self.set_type(atom.bonded_atoms[0], 'C.2')
continue
# Sulphur
if atom.get_element() == 'S':
#check for SO2
if list(bonded_elements.values()).count('O') == 2:
i1 = list(bonded_elements.values()).index('O')
i2 = list(bonded_elements.values()).index('O', i1 + 1)
self.set_type(atom.bonded_atoms[i1], 'O.2')
self.set_type(atom.bonded_atoms[i2], 'O.2')
self.set_type(atom, 'S.o2')
continue
# check for SO4
if list(bonded_elements.values()).count('O') == 4:
no_O2 = 0
for i in range(len(atom.bonded_atoms)):
if len(atom.bonded_atoms[i].bonded_atoms) == 1 and no_O2 < 2:
self.set_type(atom.bonded_atoms[i], 'O.2')
no_O2 += 1
else:
self.set_type(atom.bonded_atoms[i], 'O.3')
self.set_type(atom, 'S.3')
continue
# Phosphorous (phosphorous sp3)
#@attention: This was added and may not consider all types of phosphorous
if atom.get_element() == 'P':
self.set_type(atom, 'P.3')
continue
element = atom.get_element().capitalize()
self.set_type(atom, element)
#pka_print('Using element as type for %s'%atom.get_element())
return
def set_type(self,atom,type):
pka_print(atom,'->',type)
atom.name = type
atom.sybyl_assigned=1
return
def is_ring_member(self, atom):
return self.identify_ring(atom,atom,0,[])
def identify_ring(self, this_atom, original_atom, number, past_atoms):
number+=1
past_atoms=past_atoms+[this_atom]
return_atoms = []
for atom in this_atom.bonded_atoms:
if atom == original_atom and number>2:
return past_atoms
if atom not in past_atoms:
these_return_atoms = self.identify_ring(atom, original_atom, number, past_atoms)
if len(these_return_atoms) > 0:
if len(return_atoms)>len(these_return_atoms) or len(return_atoms)==0:
return_atoms = these_return_atoms
return return_atoms
def is_planar(self, atom):
""" Finds out if atom forms a plane together with its bonded atoms"""
atoms = [atom]+atom.bonded_atoms
return self.are_atoms_planar(atoms)
def are_atoms_planar(self, atoms):
if len(atoms)==0:
return False
if len(atoms)<4:
return False
v1 = vector(atom1=atoms[0], atom2=atoms[1])
v2 = vector(atom1=atoms[0], atom2=atoms[2])
n = (v1**v2).rescale(1.0)
margin = 0.20
for b in atoms[3:]:
v = vector(atom1=atoms[0], atom2=b).rescale(1.0)
#pka_print(atoms[0],abs(v*n) )
if abs(v*n)>margin:
return False
return True
def is_aromatic_ring(self, atoms):
if len(atoms)<5:
return False
for i in range(len(atoms)):
if not self.are_atoms_planar(atoms[i:]+atoms[:i]):
return False
return True
class ligand_residue:
def __init__(self, atoms):
self.resNumb = -1
self.resName = ''
self.atoms = atoms
if len(self.atoms)>0:
self.resNumb = self.atoms[0].resNumb
self.resName = self.atoms[0].resName
pka_print('Created ligand residue %s with %2d atoms'%(self, len(self.atoms)))
return
def __str__(self):
return '%s-%4d'%(self.resName,self.resNumb)
if __name__ == '__main__':
if len(sys.argv)<2:
sys.exit(0)
protonator = protonate.Protonate()
pka_print(sys.argv[1])
atoms = pdb.readPDB(sys.argv[1],tags=["ATOM","HETATM"])
my_ligand = ligand(atoms)
#assign sybyl names
protonator.remove_all_hydrogen_atoms_from_ligand(my_ligand)
my_ligand.assign_atom_names()
my_ligand.writePDB('before_ligand_protonation.pdb')
#convert to propka input names
# for atom in my_ligand.atoms:
# temp = atom.name
# temp = temp.replace('.','')
# if len(temp)>3:
# temp = temp[0:3]
# atom.name = temp
# protonate
protonator.protonate_ligand(my_ligand)
my_ligand.writePDB('after_ligand_protonation.pdb')
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