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#
# * 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 math, time
from . import iterative
from . import lib
from .lib import pka_print
#import debug
from . import calculator as calculate
from .determinant import Determinant
def setDeterminants(propka_residues, version=None, options=None):
"""
adding side-chain and coulomb determinants/perturbations to all residues - note, backbone determinants are set separately
"""
#debug.printResidues(propka_residues)
iterative_interactions = []
# --- NonIterative section ---#
for residue1 in propka_residues:
for residue2 in propka_residues:
if residue1 == residue2:
break
distance = calculate.InterResidueDistance(residue1, residue2)
if distance < version.sidechain_cutoff or distance < version.coulomb_cutoff[1]:
try:
do_pair, iterative_interaction = version.interaction[residue1.resType][residue2.resType]
except KeyError as e:
do_pair = False
if do_pair == True:
if iterative_interaction == True:
iterative.addtoDeterminantList(residue1, residue2, distance, iterative_interactions, version=version)
#print "%s - %s I" % (residue1.label, residue2.label)
else:
addDeterminants(residue1, residue2, distance, version=version)
#print "%s - %s" % (residue1.label, residue2.label)
else:
""" False - don't do this at home folks """
# --- Iterative section ---#
#debug.printIterativeDeterminants(iterative_interactions)
iterative.addDeterminants(iterative_interactions, version, options=options)
def addDeterminants(residue1, residue2, distance, version=None):
"""
adding determinants/perturbations, distance(R1, R2) < coulomb_cutoff always
"""
# side-chain determinant
if distance < version.sidechain_cutoff:
# Currently we don't want any hydrogen bonds to ligands
if 'ligand' not in [residue1.type, residue2.type]:
addSidechainDeterminants(residue1, residue2, version)
do_coulomb = version.checkCoulombPair(residue1, residue2, distance)
# Coulomb determinant
if do_coulomb == True:
addCoulombDeterminants(residue1, residue2, distance, version)
def addSidechainDeterminants(residue1, residue2, version=None):
"""
adding side-chain determinants/perturbations
Note, resNumb1 > resNumb2
"""
distance = 999.0
closest_atom1 = None
closest_atom2 = None
atoms1 = residue1.makeDeterminantAtomList(residue2.resName, version=version)
atoms2 = residue2.makeDeterminantAtomList(residue1.resName, version=version)
for atom1 in atoms1:
for atom2 in atoms2:
# select the smallest inter-atom distance
current_distance = calculate.InterAtomDistance(atom1, atom2)
if current_distance < distance:
closest_atom1 = atom1
closest_atom2 = atom2
distance = current_distance
dpka_max, cutoff = version.SideChainParameters[residue1.resType][residue2.resType]
if distance < cutoff[1]:
if residue2.resType in version.angularDependentSideChainInteractions:
atom3 = residue2.getThirdAtomInAngle(closest_atom2)
distance, f_angle, nada = calculate.AngleFactorX(closest_atom1, closest_atom2, atom3)
elif residue1.resType in version.angularDependentSideChainInteractions:
atom3 = residue1.getThirdAtomInAngle(closest_atom1)
distance, f_angle, nada = calculate.AngleFactorX(closest_atom2, closest_atom1, atom3)
else:
# i.e. no angular dependence
f_angle = 1.0
weight = version.calculatePairWeight(residue1.Nmass, residue2.Nmass)
exception, value = version.checkExceptions(residue1, residue2)
#exception = False # circumventing exception
if exception == True:
""" do nothing, value should have been assigned """
#pka_print(" exception for %s %s %6.2lf" % (residue1.label, residue2.label, value))
else:
value = version.calculateSideChainEnergy(distance, dpka_max, cutoff, weight, f_angle)
if residue1.Q == residue2.Q:
# acid pair or base pair
if residue1.pKa_mod < residue2.pKa_mod:
newDeterminant1 = Determinant(residue2.label, -value)
newDeterminant2 = Determinant(residue1.label, value)
else:
newDeterminant1 = Determinant(residue2.label, value)
newDeterminant2 = Determinant(residue1.label, -value)
else:
newDeterminant1 = Determinant(residue2.label, value*residue1.Q)
newDeterminant2 = Determinant(residue1.label, value*residue2.Q)
if residue1.resName not in version.exclude_sidechain_interactions:
residue1.determinants[0].append(newDeterminant1)
if residue2.resName not in version.exclude_sidechain_interactions:
residue2.determinants[0].append(newDeterminant2)
def addCoulombDeterminants(residue1, residue2, distance, version):
"""
adding NonIterative Coulomb determinants/perturbations
"""
weight = version.calculatePairWeight(residue1.Nmass, residue2.Nmass)
value = version.calculateCoulombEnergy(distance, weight)
Q1 = residue1.Q
Q2 = residue2.Q
# assigning the Coulombic interaction
if Q1 < 0.0 and Q2 < 0.0:
""" both are acids """
addCoulombAcidPair(residue1, residue2, value)
elif Q1 > 0.0 and Q2 > 0.0:
""" both are bases """
addCoulombBasePair(residue1, residue2, value)
else:
""" one of each """
addCoulombIonPair(residue1, residue2, value)
def addCoulombAcidPair(object1, object2, value):
"""
Adding the Coulomb interaction (an acid pair):
the higher pKa is raised
"""
label1 = object1.label
label2 = object2.label
if object1.pKa_mod > object2.pKa_mod:
newDeterminant = Determinant(label2, value)
object1.determinants[2].append(newDeterminant)
else:
newDeterminant = Determinant(label1, value)
object2.determinants[2].append(newDeterminant)
def addCoulombBasePair(object1, object2, value):
"""
Adding the Coulomb interaction (a base pair):
the lower pKa is lowered
"""
label1 = object1.label
label2 = object2.label
if object1.pKa_mod < object2.pKa_mod:
newDeterminant = Determinant(label2, -value)
object1.determinants[2].append(newDeterminant)
else:
newDeterminant = Determinant(label1, -value)
object2.determinants[2].append(newDeterminant)
def addCoulombIonPair(object1, object2, value):
"""
Adding the Coulomb interaction (an acid-base pair):
the pKa of the acid is lowered & the pKa of the base is raised
"""
label1 = object1.label
label2 = object2.label
# residue1
Q1 = object1.Q
newDeterminant = Determinant(label2, Q1*value)
object1.determinants[2].append(newDeterminant)
# residue2
Q2 = object2.Q
newDeterminant = Determinant(label1, Q2*value)
object2.determinants[2].append(newDeterminant)
def setIonDeterminants(protein, version=None):
"""
adding ion determinants/perturbations
"""
ionizable_residues = lib.residueList("propka1")
for residue in protein.propka_residues:
if residue.resName in ionizable_residues:
for ion in protein.residue_dictionary["ION"]:
distance = calculate.InterResidueDistance(residue, ion)
if distance < version.coulomb_cutoff[1]:
label = "%s%4d%2s" % (ion.resName, ion.resNumb, ion.chainID)
weight = version.calculatePairWeight(residue.Nmass, ion.Nmass)
# the pKa of both acids and bases are shifted up by negative ions (and vice versa)
value = (-ion.Q) * version.calculateCoulombEnergy(distance, weight)
newDeterminant = Determinant(label, value)
residue.determinants[2].append(newDeterminant)
def setBackBoneDeterminants(backbone_interactions, version=None):
"""
adding back-bone determinants/perturbations
Angle: atom1 -- atom2-atom3
backbone_interactions = [[acids, NH], [bases, CO]]
changing the code with minimum effect of method calls
"""
setBackBoneAcidDeterminants(backbone_interactions[0], version=version)
setBackBoneBaseDeterminants(backbone_interactions[1], version=version)
def setBackBoneAcidDeterminants(data_clump, version=None):
"""
adding back-bone determinants/perturbations for acids:
Angle: atom1 -- atom2-atom3, i.e. COO -- H-N
data_clump = [acids, NH]
"""
residues, interactions = data_clump
for residue in residues:
if residue.location != "BONDED":
dpKa_max, cutoff = version.BackBoneParameters[residue.resType]
for interaction in interactions:
atom2 = interaction[1]
atom3 = interaction[0]
atoms = residue.makeDeterminantAtomList("back-bone", version=version)
shortest_distance = 999.
for atom in atoms:
distance = calculate.InterAtomDistance(atom, atom2)
if distance < shortest_distance:
shortest_distance = distance
atom1 = atom
distance, f_angle, nada = calculate.AngleFactorX(atom1, atom2, atom3)
if distance < cutoff[1] and f_angle > 0.001:
label = "%s%4d%2s" % (atom2.resName, atom2.resNumb, atom2.chainID)
value = residue.Q * calculate.HydrogenBondEnergy(distance, dpKa_max, cutoff, f_angle)
newDeterminant = Determinant(label, value)
residue.determinants[1].append(newDeterminant)
def setBackBoneBaseDeterminants(data_clump, version=None):
"""
adding back-bone determinants/perturbations for bases:
Angle: atom1 -- atom2-atom3, i.e. C=O -- H-N(HIS)
data_clump = [bases, CO]
"""
residues, interactions = data_clump
for residue in residues:
if residue.location != "BONDED":
dpKa_max, cutoff = version.BackBoneParameters[residue.resType]
for interaction in interactions:
distance = 999.
atom1 = interaction[1]
atoms = residue.makeDeterminantAtomList("back-bone", version=version)
for atom in atoms:
current_distance = calculate.InterAtomDistance(atom1, atom)
if current_distance < distance:
atom2 = atom
distance = current_distance
if distance < cutoff[1]:
if residue.resType in version.angularDependentSideChainInteractions:
atom3 = residue.getThirdAtomInAngle(atom2)
distance, f_angle, nada = calculate.AngleFactorX(atom1, atom2, atom3)
else:
f_angle = 1.0
if f_angle > 0.001:
# add determinant
label = "%s%4d%2s" % (atom2.resName, atom2.resNumb, atom2.chainID)
value = residue.Q * calculate.HydrogenBondEnergy(distance, dpKa_max, cutoff, f_angle)
newDeterminant = Determinant(label, value)
residue.determinants[1].append(newDeterminant)
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