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WaterProcessing.py
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WaterProcessing.py
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#
# AutoDock | Raccoon2
#
# Copyright 2013, Stefano Forli
# Molecular Graphics Lab
#
# The Scripps Research Institute
# _
# (,) T h e
# _/
# (.) S c r i p p s
# \_
# (,) R e s e a r c h
# ./
# ( ) I n s t i t u t e
# '
#
# This program is free software: you can redistribute it and/or modify
# it under the terms of the GNU General Public License as published by
# the Free Software Foundation, either version 3 of the License, or
# (at your option) any later version.
#
# This program 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 General Public License for more details.
#
# You should have received a copy of the GNU General Public License
# along with this program. If not, see <http://www.gnu.org/licenses/>.
#
#
# water related code
# v.0.1 start 26.1.2012
# v.0.2 rewritten class 2012.4.11
#
#
"""
- is RECEPTOR available?
- is EXP_WAT available?
- is WAT_MAP available?
-for each pose:
- clean LIG/LIG overlaps ( DeltaS = map_point )
- clean LIG/REC overlaps ( DeltaS = map_point )
####### - clean FREE WATERS ( DeltaS = map_point ) ???
####### - score BRIDGING WATERS ( DeltaH - DeltaS )
- score BRIDGING WATERS ( DeltaH - DeltaS )
FREE WATERS issue:
- are more favorable for a ligand, hence they should be kept?
- are less favorab
"""
import HelperFunctionsN3P as hf
from numpy import array
#CLASH = 2.03 # min. distance between W and real atoms (lig, rec) # XXX to remove spurious water in 2zye
#CLASH = 2.15 # min. distance between W and real atoms (lig, rec)
LONELINESS_DISTANCE = 3.5 # to be used to remove lone waters not interacting with anything..b
# TODO add a function to renumber the PDBQT after removing waters?
# XXX MAKE IT A CLASS!!!
class processHydroDocking:
def __init__(self, pose=None, # advanced pose to process [text, coords, water_bridge, ...]
gridmap=None, # grid map (file/dictionary)
# distance parms
mapdistrange=1.0, # distance around W coords to look for grid points
clust_tol = 2.0, # cluster tolerance
interact_dist = 3.5, # W-RecAtom interaction distance
clash= 2.03, # min.distance allowed between W/atoms (lig, rec) # XX to remove spurious watre
loneliness_dist = 3.5, # max distance between W and interacting rec atoms
# energy parms
cutoff_weak = -0.35, # weak water e.cutoff
cutoff_strong = -0.5, # strong water e.cutoff
desolvEntropy=-0.2, # desolvation entropy
conservedwaterentropy=0, # add an entropy penalty also for conserved waters
ignore_types = ['H', 'HD', 'W'], # atoms ignored for lig_overlap
debug = False): # ignore atom types for contacts
if gridmap == None:
#raise "No water map provided"
print "No water map provided"
return False
print "WARNING processHydroDocking:_init_> clash distance [%2.3f] is extremely low! Test with some case studies" % clash
self.gridmap = gridmap
self.pose = pose
self.mapdistrange = mapdistrange
self.clust_tol = clust_tol
self.interact_dist = interact_dist
self.clash = clash
self.loneliness_dist = loneliness_dist
self.cutoff_weak = cutoff_weak
self.cutoff_strong = cutoff_strong
self.desolvEntropy = desolvEntropy
self.ignore_types = ignore_types
self.conservedwaterentropy = conservedwaterentropy
self.qs = hf.QuickStop()
self.debug = debug
if not (pose == None) and not (gridmap == None):
self.process
def process(self):
# w-lig overlap -> ['water_lig_over']
self.ligOverlapWaters()
# w-rec overlap -> ['water_rec_over']
self.recOverlapWaters()
# get energies for ['water_bridge_score'], ['water_lig_over_penalty'], ['water_rec_over_penalty']
self.getWaterGridEnergy()
# cluster ['water_bridge']
self.clusterWaters()
# clean-up extra_weak waters (increment ['water_rec_over_penalty'], if necessary
self.weakWaterCleanup()
# score waters and update PDBQT
self.rankWaters()
# normalize ligand energy poses['e'] ; poses['leff']
self.normalizeWaterScore()
return self.pose
def getMapPoints(self, coords=None, distance=1.0): # mapdata, coords=None, distance=1.0):
""" get points around (distance) of coordinates (coords)
"""
# XXX TODO it should become interpolator!
if coords == None:
print "getMapPoints> ERROR: no coordinates!"
return False
data = self.gridmap['values']
v_min = self.gridmap['min']
v_max = self.gridmap['max']
spacing = self.gridmap['spacing']
pts = self.gridmap['pts']
harvesting = []
pt_scan = int( round(float(distance)/(spacing)) )
if pt_scan == 0: pt_scan = 1 # at least one point around
if self.debug: print "Grid range: %2.2f [ +/- %d points : %2.2f ]" % (distance,pt_scan, pt_scan*spacing),
best = 0
warning_issued = False
if (coords[0] < v_max[0]) and (coords[0] > v_min[0]):
if (coords[1] < v_max[1]) and (coords[1] > v_min[1]):
if (coords[2] < v_max[2]) and (coords[2] > v_min[2]):
z_pt = int(round((coords[2] - v_min[2])/spacing))
y_pt = int(round((coords[1] - v_min[1])/spacing))
x_pt = int(round((coords[0] - v_min[0])/spacing))
for x_ofs in range(-pt_scan, pt_scan+1):
x = x_pt + x_ofs
if x < 0 :
harvesting.append(0)
break
for y_ofs in range(-pt_scan, pt_scan+1):
y = y_pt + y_ofs
if y < 0 :
harvesting.append(0)
break
for z_ofs in range(-pt_scan, pt_scan+1):
z = z_pt + z_ofs
if z < 0 :
harvesting.append(0)
break
try:
harvesting.append( data[z,y,x] )
if data[z,y,x] < best:
best = data[z,y,x]
except:
if not warning_issued:
msg = ('*** WaterProcessing> Warning! '
'Wat(%2.3f,%2.3f,%2.3f) '
'close to gridbox edge ***' % (coords[0], coords[1], coords[2])
)
best = 0
print msg
warning_issued = True
harvesting.append( 0 )
if self.debug: print "genMapPoints> %d pts [ best: %2.2f ]" % (len(harvesting), best),
return harvesting, best
return False
def ligOverlapWaters(self):
"""
remove ligand-overlapping w-atoms in a pose
"""
#, cutoff = CLASH,
ignore_types = self.ignore_types
#ignore_types = [ 'W' ]
# add a larger tolerance for HD?
#cutoff = 2.4
cutoff = self.clash ** 2
log = []
overlapping = []
for w in self.pose['water_bridge']:
try:
for a in self.pose['text']:
if not w == a:
if isAtom(a) and (not getAtype(a) in self.ignore_types):
d = dist(w, a, sq=0)
#if d < self.clash:
if d < cutoff:
overlapping.append(w)
self.pose['text'].remove(w)
raise self.qs
except:
pass
if self.debug:
print "Processed: %d | Lig-overlap %d" % (len(self.pose['water_bridge']), len(overlapping) )
for w in overlapping:
idx = self.pose['water_bridge'].index(w)
self.pose['water_bridge'].remove(w)
self.pose['water_bridge_contacts'].pop(idx)
self.pose['water_over_lig'] = overlapping
def recOverlapWaters(self): # pose, cutoff = CLASH,
#ignore_types = ['HD', 'H', 'W'] ):
""" INPUT : pdb lig (multi)model and pdb target model
OUTPUT: cleaned pdb lig model
"""
#print "WARNING! missing interactions! Line B1"
overlapping = []
atom_pool = []
cutoff = self.clash**2
#cutoff += 0.5
#cutoff = 0
#for a in self.pose['vdw_contacts']: # PDBQT, no-HD # XXX TODO BUG Line B1
for aset in self.pose['water_bridge_contacts']: # PDBQT, no-HD # XXX TODO BUG Line B1
for a in aset:
if not hf.getAtype(a) in self.ignore_types:
atom_pool.append(a)
if self.debug:
fp = open('DEBUG_rec_overlap.pdb','w')
fp.write("REMARK WATERS REMOVED BY RECEPTOR CLASHES")
for w in self.pose['water_bridge']:
try: # try/except is faster
for a in atom_pool:
#if hf.dist(w, a, sq=False) < self.clash:
if hf.dist(w, a, sq=False) < cutoff:
overlapping.append(w)
self.pose['text'].remove(w)
#print "\n\n\n #### REMOVED", w
if self.debug:
fp.write(w+"\n")
fp.write(a+"\n")
raise self.qs
except:
pass
if self.debug:
fp.close()
print "Processed: %d | Rec-overlap %d" % (len(self.pose['water_bridge']), len(overlapping) )
for w in overlapping:
idx = self.pose['water_bridge'].index(w)
del self.pose['water_bridge_contacts'][idx]
self.pose['water_bridge'].remove(w)
self.pose['water_over_rec'] = overlapping
def getWaterGridEnergy(self):
# cutoff_weak = -0.35, # weak water e.cutoff
# cutoff_strong = -0.5, # strong water e.cutoff
# desolvEntropy=-0.2, # desolvation entropy
# mapdistrange = 0.5):
# TODO to be used to 'minimize' the water position too?
# looking for the best spot for a water
# and increase the energy accordingly?
# calculate the score for bridging waters;
self.pose['water_bridge_scores'] = []
for w in self.pose['water_bridge']:
points, best_point = self.getMapPoints( coords = hf.atomCoord(w),
distance = self.mapdistrange)
self.pose['water_bridge_scores'].append(best_point)
# calculate ligand-overlapping penalties
self.pose['water_over_lig_penalty'] = []
for w in self.pose['water_over_lig']:
points, best_point = self.getMapPoints( coords = atomCoord(w),
distance = self.mapdistrange)
self.pose['water_over_lig_penalty'].append( -best_point)
# calculate rec-overlapping penalties
self.pose['water_over_rec_penalty'] = []
for w in self.pose['water_over_rec']:
self.pose['water_over_rec_penalty'].append(-self.desolvEntropy)
def clusterWaters(self): #pose, clust_tolerance=2.0, desolvEntropy=0):
# cluster waters
# XXX
# energy from the cluster?
# once 3 waters are reclustered (3->1)
# two desolvEntropy penalties should be issued?
# XXX
unclustered_waters = self.pose['water_bridge'][:] # XXX NOT SURE IT"S NECESSARY
# cluster waters
water_clusters = hf.clusterAtoms(unclustered_waters, tol=self.clust_tol)
# calculate clustering energy
self.pose['water_cluster_penalty'] = []
remove_from_text = []
for pop in water_clusters:
if len(pop)>1:
this_cluster_centroid = hf.avgCoord(pop)
this_cluster_penalty = -self.desolvEntropy * (len(pop)-1)
this_cluster_energy = 0
this_cluster_contacts = []
closest_to_centroid = None
closest_dist = 999999
for w in pop:
# get the w_index + w_score
idx = self.pose['water_bridge'].index(w)
this_cluster_energy += self.pose['water_bridge_scores'][idx]
remove_from_text.append(w)
# find water closest to centroid (to be conserved)
# get the distance from the cluster average
centr_dist = hf.quickdist( hf.atomCoord(w), this_cluster_centroid, sq = False)
a = [ hf.makePdb(coord=this_cluster_centroid) ]
#writeList('centroid.pdb', a)
if centr_dist <= closest_dist:
closest_dist = centr_dist
closest_to_centroid = w
del self.pose['water_bridge'][idx]
del self.pose['water_bridge_scores'][idx]
# update contacts
for a in self.pose['water_bridge_contacts'][idx]:
if not a in this_cluster_contacts:
this_cluster_contacts.append(a)
del self.pose['water_bridge_contacts'][idx]
# update PDBQT text
# XXX DEBUGGINGH
#print type(remove_from_text), remove_from_text[0]
#writeList('REMOVING_WATERS.pdb', remove_from_text)
#writeList('current_ligand.pdbqt', pose['text'])
for w in remove_from_text:
if not w == closest_to_centroid:
try:
text_idx = self.pose['text'].index(w)
del self.pose['text'][text_idx]
except:
pass
# use the closest to be updated with clustering coords
closest_index = self.pose['text'].index(closest_to_centroid)
water = self.pose['text'][closest_index]
coord_text = "%8.3f%8.3f%8.3f" % (this_cluster_centroid[0],
this_cluster_centroid[1],
this_cluster_centroid[2])
cluster_water = water[0:30]+coord_text+water[54:] # XXX ugly, but it works...
self.pose['text'][closest_index] = cluster_water
# update water_bridge list+score, water_cluster_penalty list
self.pose['water_bridge'].append(cluster_water)
self.pose['water_bridge_scores'].append(this_cluster_energy)
self.pose['water_cluster_penalty'].append(this_cluster_penalty)
self.pose['water_bridge_contacts'].append(this_cluster_contacts)
if self.debug:
print "CLUSTER SIZE", len(pop)
print "CLUSTER ENRG", this_cluster_energy
print "CLUSTER PENL", this_cluster_penalty
#print "CLUSTER FINL", clust_energy+clust_penalty
print "=============="
def normalizeWaterScore(self): #pose,entropyPenalty=False):
# keep track of the original energy values
if self.debug:
old_e = self.pose['energy']
old_leff = self.pose['leff']
# rec_displaced waters
rec_displaced = 0
for p in self.pose['water_over_rec_penalty']:
rec_displaced += p
# print p # XXX
#print "RECDISP", rec_displaced # XXX
# lig_displaced waters
lig_displaced = 0
for p in self.pose['water_over_lig_penalty']:
lig_displaced += p
# clustering-displaced
clust_displaced = 0
for p in self.pose['water_cluster_penalty']:
clust_displaced += p
# count heavy at for lig.efficiency
heavy_atoms = 0
for a in self.pose['text']:
if hf.isAtom(a) and ( not hf.getAtype(a) in ['HD', 'W'] ):
heavy_atoms += 1
# energy correction
if self.conservedwaterentropy:
# XXX read the penalty from a variable!
entropy = (0.2)*len(self.pose['water_bridge'])
#print " ENTROPY PENALTY = ", entropy
else:
entropy = 0
self.pose['energy'] += lig_displaced + rec_displaced + clust_displaced + entropy
# lig.efficiency correction
self.pose['leff'] = self.pose['energy'] / float( heavy_atoms )
if self.debug:
#print "\n# PENALTY:\t +%2.3f [rec: %2.3f, lig: %2.3f, clust: %2.3f ]" % (rec_displaced+lig_displaced+clust_displaced,
# rec_displaced, lig_displaced, clust_displaced)
print " Penalties:"
print " - lig overlap : %2.3f" % lig_displaced
print " - rec overlap : %2.3f" % rec_displaced
print " - cluster penalty : %2.3f" % clust_displaced
print " - extra entropy : %2.3f" % entropy
print " ENERGY:\t %2.3f [ old: %2.3f ]" % (self.pose['energy'], old_e)
print " L.EFF.:\t %2.3f [ old: %2.3f ]\n" % (self.pose['leff'], old_leff)
#return pose
def rankWaters(self): #pose, cutoff_weak, cutoff_strong):
# keep track of the original energy values
if self.debug:
old_e = pose['energy']
old_leff = pose['leff']
rank_line = "REMARK %s water ( score: %2.2f )\n"
self.pose['water_bridge_rank'] = []
for idx in range(len(self.pose['water_bridge'])):
water = self.pose['water_bridge'][idx]
score = self.pose['water_bridge_scores'][idx]
if score < self.cutoff_strong:
# strongly bound
rank = 'STRONG'
score_comment = rank_line % (rank, score)
elif score < self.cutoff_weak:
# weakly bound
rank = 'WEAK'
score_comment = rank_line % (rank, score)
else:
# transient trapped/bulk water
rank = 'TRAPPED/BULK'
score_comment = rank_line % (rank, score)
self.pose['water_bridge_rank'].append( [ rank, score ])
# update the PDBQT text
mark = self.pose['text'].index(water)
txt = self.pose['text'][mark]
self.pose['text'][mark] = score_comment + txt
if self.debug:
for w in self.pose['water_bridge_rank']:
print "W:", w
def weakWaterCleanup(self): #
#pose, cutoff_weak = -0.35, cutoff_strong=-0.5, interact_dist=3.5 ):
""" clean-up extra_weak waters (increment ['water_rec_over_penalty'], if necessary"""
org_waters = len(self.pose['water_bridge'])
#ignore_types = ['HD']
lone_water = []
interact_dist = self.interact_dist**2
hb_types = ['OA', 'NA', 'SA', 'N', 'O', 'OA', 'NA', 'SA']
hb_types += hf.METALS
for idx in range(len(self.pose['water_bridge'])):
water = self.pose['water_bridge'][idx]
score = self.pose['water_bridge_scores'][idx]
# analyze only waters that are not ranked strong
if score >= self.cutoff_strong:
atom_pool = [ a for a in self.pose['water_bridge_contacts'][idx] if hf.getAtype(a) in hb_types]
if self.debug:
hf.writeList('ATOM_POOL_%d_HB_%d.pdb' % (idx, sess), atom_pool, addNewLine=True)
lone_water.append(water)
try:
for a in atom_pool:
if (dist(water, a, sq=0)<= interact_dist):
#print "FOUND MATE",
#print dist(water, a, sq=True)
#print a.strip()
#print "------------------"
raise self.qs
#print "NO MATE FOR THIS", score
#print water.strip()
except:
lone_water.remove(water)
for w in lone_water:
idx = self.pose['water_bridge'].index(w)
del self.pose['water_bridge'][idx]
del self.pose['water_bridge_contacts'][idx]
# EXPERIMENTAL
#w_score = self.pose['water_bridge_scores'][idx]
#if w_score >
# XXX THIS shouldn't happen:
# a weakly bound water could be hanging in the bulk, but it should be accounted for
# ...?
# how to describe the bulk solvent?
# combine desolv map + discrete waters?
#
self.pose['water_over_rec_penalty'].append( -self.pose['water_bridge_scores'].pop(idx) )
# update PDBQT text
#print pose['water_over_rec_penalty'] # XXX
text_idx = self.pose['text'].index(w)
del self.pose['text'][text_idx]
if self.debug:
print "LONE WATERS # REMOVED: ", (org_waters- len(self.pose['water_bridge']) )