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Greg Landrum
202
Contrib/M_Kossner/BaseFeatures_DIP2_NoMicrospecies.fdef
Executable file
202
Contrib/M_Kossner/BaseFeatures_DIP2_NoMicrospecies.fdef
Executable file
@@ -0,0 +1,202 @@
|
||||
# $Id$
|
||||
#
|
||||
# FDef file contributed by Markus Kossner
|
||||
|
||||
AtomType AcidicN [$([NH,N-1](S(=O))(C(=O))),$([NH,N-1](C(=O))(C(=O))),$([NH,N-1](S(=O)(=O))c),$([NH2]S(=O)(=O)c)]
|
||||
AtomType AmideN [$([#7]-C(=O))]
|
||||
AtomType AmidineTripleN [$([#7]-C(=[#7]))]
|
||||
AtomType SulfonamideN [$([N;H0]S(=O)(=O))]
|
||||
AtomType NDonor [N&!H0&v3,N&!H0&+1&v4,n&H1&+0;!{AcidicN};!{AmidineTripleN}]
|
||||
AtomType NDonor [$([Nv3](-C)(-C)-C);!{AmideN};!{AmidineTripleN}] #Primary Amine but not Amide!
|
||||
AtomType NDonor [$(n[n;H1]),$(nc[n;H1]);!{AcidicN}]
|
||||
|
||||
AtomType AcidicHydroxyl [$([O]C(=[O,S,P]))]
|
||||
AtomType ChalcDonor [O,S;H1;+0]
|
||||
DefineFeature SingleAtomDonor [{NDonor},{ChalcDonor};!{AcidicHydroxyl}]
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||||
Family Donor
|
||||
Weights 1
|
||||
EndFeature
|
||||
|
||||
# aromatic N, but not indole or pyrole or fusing two rings or tetrazole
|
||||
AtomType NAcceptor [$([N;H0]#,=[C&v4])]
|
||||
AtomType NAcceptor [n;+0;H0;!X3] #;!$([n](n)) !$([n;H1](cc)cc)
|
||||
# tertiary nitrogen adjacent to aromatic carbon
|
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AtomType NAcceptor [N&v3;H0;$(Nc)]
|
||||
|
||||
# removes ether, thioether and nitro oxygen
|
||||
AtomType ChalcAcceptor [O;H0;!$(O=N-*);!$([OD2]([#6])[#6])]
|
||||
|
||||
# Removed aromatic sulfur from ChalcAcceptor definition
|
||||
#We will not use aromatic oxygens! cf Leach, Gillet ... J Med Chem 2010,53, 539-558
|
||||
#Atomtype ChalcAcceptor [o;+0]
|
||||
|
||||
# Hydroxyls and acids
|
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AtomType Hydroxyl [O;H1;v2]
|
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|
||||
# F is an acceptor so long as the C has no other halogen neighbors. This is maybe
|
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# a bit too general, but the idea is to eliminate things like CF3
|
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AtomType HalogenAcceptor [F;$(F-[#6]);!$(FC[F,Cl,Br,I])]
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DefineFeature SingleAtomAcceptor [{Hydroxyl},{ChalcAcceptor},{NAcceptor},{HalogenAcceptor}]
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Family Acceptor
|
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Weights 1
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EndFeature
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# this one is NOT delightfully easy :-)
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#We wil define some additional NegIonizable Features
|
||||
#I later found some similar substructures in
|
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# Good,Oprea J.Comput.Aided.Mol.Des (2008) 22:169-178:
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DefineFeature AcidicGroup [C,S,P](=[O,S])-[O;H1,H0&-1]
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Family NegIonizable
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Weights 1.0,1.0,1.0
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EndFeature
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DefineFeature AcidicN [{AcidicN};!$([nH,n-1]1cnnn1)]
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Family NegIonizable
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Weights 1,0,1,1,0,0
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EndFeature
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DefineFeature Tetrazole c1nnn[nH,n-1]1
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Family NegIonizable
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Weights 1,1,1,1,1
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EndFeature
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AtomType Carbon_NotDouble [C;!$(C=*)]
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AtomType BasicNH2 [$([N;H2&+0;!R][{Carbon_NotDouble}])]
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AtomType BasicNH1 [$([N;H1&+0;!R]([{Carbon_NotDouble}])[{Carbon_NotDouble}])]
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AtomType BasicNH0 [$([N;H0&+0;!R]([{Carbon_NotDouble}])([{Carbon_NotDouble}])[{Carbon_NotDouble}])]
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#AtomType QuatN [$([N;H0&+1]([{Carbon_NotDouble}])([{Carbon_NotDouble}])([{Carbon_NotDouble}])[{Carbon_NotDouble}])]
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DefineFeature BasicGroup [{BasicNH2},{BasicNH1},{BasicNH0};!$(N[a])]
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Family PosIonizable
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Weights 1.0
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EndFeature
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# 14.11.2007 (GL): add !$([N+]-[O-]) constraint so we don't match
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# nitro (or similar) groups
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DefineFeature PosN [#7;+;!$([N+]-[O-])]
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Family PosIonizable
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Weights 1.0
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EndFeature
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#Define electronegative atoms that might have an impact on pka of moieties otherwise basic?
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AtomType ElectroNegative [N,n,O,o,F,Cl,Br]
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# imidazole group can be positively charged (too promiscuous?)
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#DefineFeature Imidazole [n,+0]1[$(cC),$([cH])][n;+0][$(cC),$([cH])][$(cC),$([cH])]1
|
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# Family PosIonizable
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||||
# Weights 1.0,1.0,1.0,1.0,1.0
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#EndFeature
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# guanidine group is positively charged (too promiscuous? We do not match any aromatic systems here. That would be too promiscuous!)
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DefineFeature Guanidine [N;+0;!{AmideN}][#6;+0](=[N;+0;!{AmideN}])[N;+0;!{AmideN}]
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Family PosIonizable
|
||||
Weights 1.0,1.0,1.0,1.0
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||||
EndFeature
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||||
|
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# amidine group is positively charged (too promiscuous?)
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DefineFeature Amidine [N;+0;!{AmideN}][#6]=,:[#7;+0;!$(ncn);!{AmideN}]
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Family PosIonizable
|
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Weights 1.0,1.0,1.0
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||||
EndFeature
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# aromatic rings of various sizes:
|
||||
#
|
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# Note that with the aromatics, it's important to include the ring-size queries along with
|
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# the aromaticity query for two reasons:
|
||||
# 1) Much of the current feature-location code assumes that the feature point is
|
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# equidistant from the atoms defining it. Larger definitions like: a1aaaaaaaa1 will actually
|
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# match things like 'o1c2cccc2ccc1', which have an aromatic unit spread across multiple simple
|
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# rings and so don't fit that requirement.
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# 2) It's *way* faster.
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# 21.1.2008 (GL): update ring membership tests to reflect corrected meaning of
|
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# "r" in SMARTS parser
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#
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AtomType AromR4 [a;r4,!R1&r3]
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DefineFeature Arom4 [{AromR4}]1:[{AromR4}]:[{AromR4}]:[{AromR4}]:1
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Family Aromatic
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Weights 1.0,1.0,1.0,1.0
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||||
EndFeature
|
||||
AtomType AromR5 [a;r5,!R1&r4,!R1&r3]
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DefineFeature Arom5 [{AromR5}]1:[{AromR5}]:[{AromR5}]:[{AromR5}]:[{AromR5}]:1
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Family Aromatic
|
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Weights 1.0,1.0,1.0,1.0,1.0
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EndFeature
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AtomType AromR6 [a;r6,!R1&r5,!R1&r4,!R1&r3]
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DefineFeature Arom6 [{AromR6}]1:[{AromR6}]:[{AromR6}]:[{AromR6}]:[{AromR6}]:[{AromR6}]:1
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Family Aromatic
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Weights 1.0,1.0,1.0,1.0,1.0,1.0
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EndFeature
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AtomType AromR7 [a;r7,!R1&r6,!R1&r5,!R1&r4,!R1&r3]
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DefineFeature Arom7 [{AromR7}]1:[{AromR7}]:[{AromR7}]:[{AromR7}]:[{AromR7}]:[{AromR7}]:[{AromR7}]:1
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Family Aromatic
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Weights 1.0,1.0,1.0,1.0,1.0,1.0,1.0
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||||
EndFeature
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AtomType AromR8 [a;r8,!R1&r7,!R1&r6,!R1&r5,!R1&r4,!R1&r3]
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DefineFeature Arom8 [{AromR8}]1:[{AromR8}]:[{AromR8}]:[{AromR8}]:[{AromR8}]:[{AromR8}]:[{AromR8}]:[{AromR8}]:1
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Family Aromatic
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Weights 1.0,1.0,1.0,1.0,1.0,1.0,1.0,1.0
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EndFeature
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# hydrophobic features
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# any carbon that is not bonded to a polar atom is considered a hydrophobe
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#
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# 23.11.2007 (GL): match any bond (not just single bonds); add #6 at
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# beginning to make it more efficient
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AtomType Carbon_Polar [#6;$([#6]~[#7,#8,#9])]
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# 23.11.2007 (GL): don't match charged carbon
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AtomType Carbon_NonPolar [#6;+0;!{Carbon_Polar}]
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# 6.2009 (MK): aromatic c is not per se a hydrophobic atom
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#AtomType RingHphobe [R;{Hphobe}]
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AtomType Hphobe [s,S&H0&v2,Br,I,Cl,F,{Carbon_NonPolar}]
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# 8.2009 (MK): update 'Hydrophobes'
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DefineFeature Hphobe [{Hphobe}{Hphobe}]
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Family Hydrophobe
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Weights 1.0
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EndFeature
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# 8.2009 (MK):
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DefineFeature Methyl [CH3]
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Family Hydrophobe
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Weights 1.0
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EndFeature
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# nitro groups in the RD code are always: *-[N+](=O)[O-]
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DefineFeature Nitro2 [N;D3;+](=O)[O-]
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Family LumpedHydrophobe
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Weights 1.0,1.0,1.0
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EndFeature
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DefineFeature ThreeWayAttach [D3,D4]
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Family LumpedHydrophobe
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Weights 1.0
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EndFeature
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DefineFeature ChainEnd [R0;D1][R0;D2]
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Family LumpedHydrophobe
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Weights 1.0,1.0
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EndFeature
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# 5.2009 (MK): update ring membership tests to reflect 'Lumped Hydrophobes'
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AtomType Ring6 [r6,!R1&r5,!R1&r4,!R1&r3]
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DefineFeature R6_6 [{Ring6}]1[{Ring6}][{Ring6}][{Ring6}][{Ring6}][{Ring6}]1
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Family LumpedHydrophobe
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Weights 1.0,1.0,1.0,1.0,1.0,1.0
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EndFeature
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AtomType Ring5 [r5,!R1&r4,!R1&r3]
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DefineFeature R5_5 [{Ring5}]1[{Ring5}][{Ring5}][{Ring5}][{Ring5}]1
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Family LumpedHydrophobe
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Weights 1.0,1.0,1.0,1.0,1.0
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EndFeature
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AtomType Ring4 [r4,!R1&r3]
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DefineFeature H4_4 [{Ring4}]1[{Ring4}][{Ring4}][{Ring4}]1
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Family LumpedHydrophobe
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Weights 1.0,1.0,1.0,1.0
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EndFeature
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AtomType Ring3 [r3]
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DefineFeature R3_3 [{Ring3}]1[{Ring3}][{Ring3}]1
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Family LumpedHydrophobe
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Weights 1.0,1.0,1.0
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EndFeature
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141
Contrib/M_Kossner/Frames.py
Normal file
141
Contrib/M_Kossner/Frames.py
Normal file
@@ -0,0 +1,141 @@
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#!/usr/bin/env python2.6
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# encoding: utf-8
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# $Id$
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# original author: Markus Kossner
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import os,sys
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from Chem import AllChem as Chem
|
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|
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def flatten(x):
|
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"""flatten(sequence) -> list
|
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Returns a single, flat list which contains all elements retrieved
|
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from the sequence and all nested sub-sequences (iterables).
|
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Examples:
|
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>>> [1, 2, [3,4], (5,6)]
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[1, 2, [3, 4], (5, 6)]
|
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>>> flatten([[[1,2,3], (42,None)], [4,5], [6], 7, MyVector(8,9,10)])
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[1, 2, 3, 42, None, 4, 5, 6, 7, 8, 9, 10]"""
|
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result = []
|
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for el in x:
|
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if hasattr(el, "__iter__") and not isinstance(el, basestring):
|
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result.extend(flatten(el))
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else:
|
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result.append(el)
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return result
|
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|
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def GetFrame(mol,mode='RedScaff'):
|
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'''return a ganeric molecule defining the reduced scaffold of the molecule.
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mode can be 'RedScaff' and 'Scaff'. The second mode will turn every atom to a carbon and every bond to a single bond!'''
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||||
ring=mol.GetRingInfo()
|
||||
RingAtoms= flatten(ring.AtomRings())
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NonRingAtoms=[ atom.GetIdx() for atom in mol.GetAtoms() if atom.GetIdx() not in RingAtoms ]
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RingNeighbors=[]
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Paths=[]
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for NonRingAtom in NonRingAtoms:
|
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for neighbor in mol.GetAtomWithIdx(NonRingAtom).GetNeighbors():
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if neighbor.GetIdx() in RingAtoms:
|
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RingNeighbors.append(NonRingAtom)
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Paths.append([neighbor.GetIdx(),NonRingAtom]) #The ring Atoms having a non ring Nieghbor will be the start of a walk
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break
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PosLinkers=[x for x in NonRingAtoms if x not in RingNeighbors] #Only these Atoms are Possible Linkers of two rings
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Framework=[ x for x in RingAtoms ]
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Linkers=[]
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while len(Paths)>0:
|
||||
NewPaths=[]
|
||||
for P in Paths:
|
||||
if P==None:
|
||||
print 'ooh, there is still a bug somewere '
|
||||
else:
|
||||
for neighbor in mol.GetAtomWithIdx(P[-1]).GetNeighbors():
|
||||
if neighbor.GetIdx() not in P:
|
||||
if neighbor.GetIdx() in NonRingAtoms:
|
||||
n=P[:]
|
||||
n.append(neighbor.GetIdx())
|
||||
NewPaths.append(n[:])
|
||||
elif neighbor.GetIdx() in RingAtoms:
|
||||
n=P[:]
|
||||
n.append(neighbor.GetIdx())
|
||||
Linkers.append(n)
|
||||
Framework=Framework+P[:]
|
||||
|
||||
Paths=NewPaths[:]
|
||||
#print 'Linkers:',Linkers
|
||||
#print 'RingAtoms:',RingAtoms
|
||||
if mode=='Scaff':
|
||||
Framework=list(set(Framework))
|
||||
todel=[]
|
||||
NonRingAtoms.sort(reverse=True)
|
||||
em=Chem.EditableMol(mol)
|
||||
BondsToAdd=[ sorted([i[0],i[-1]]) for i in Linkers ]
|
||||
mem=[]
|
||||
for i in BondsToAdd:
|
||||
if i not in mem:
|
||||
em.AddBond(i[0],i[1],Chem.BondType.SINGLE)
|
||||
mem.append(i)
|
||||
for i in NonRingAtoms:
|
||||
todel.append(i)
|
||||
for i in todel:
|
||||
em.RemoveAtom(i)
|
||||
m=em.GetMol()
|
||||
return m
|
||||
|
||||
if mode=='RedScaff':
|
||||
Framework=list(set(Framework))
|
||||
todel=[]
|
||||
NonRingAtoms.sort(reverse=True)
|
||||
for i in NonRingAtoms:
|
||||
if i != None:
|
||||
if i not in Framework:
|
||||
todel.append(i)
|
||||
em=Chem.EditableMol(mol)
|
||||
for i in todel:
|
||||
em.RemoveAtom(i)
|
||||
m=em.GetMol()
|
||||
#===================================#
|
||||
#Now do the flattening of atoms and bonds!
|
||||
#Any heavy atom will become a carbon and any bond will become a single bond!! #
|
||||
#===================================#
|
||||
for atom in m.GetAtoms(): #
|
||||
atom.SetAtomicNum(6) #
|
||||
atom.SetFormalCharge(0) #
|
||||
for bond in m.GetBonds(): #
|
||||
bond.SetBondType(Chem.BondType.SINGLE) #
|
||||
Chem.SanitizeMol(m) #
|
||||
#===================================#
|
||||
return m
|
||||
|
||||
if len(sys.argv) < 2:
|
||||
print "No input file provided: Frames.py <file-to-process.sdf>"
|
||||
sys.exit(1)
|
||||
|
||||
suppl=Chem.SDMolSupplier(sys.argv[1])
|
||||
|
||||
FrameDict={}
|
||||
|
||||
for mol in suppl:
|
||||
if mol == 'None': continue
|
||||
try:
|
||||
m=GetFrame(mol,mode='RedScaff')
|
||||
if FrameDict.has_key(Chem.MolToSmiles(m)):
|
||||
FrameDict[Chem.MolToSmiles(m)].append(mol)
|
||||
else:
|
||||
FrameDict[Chem.MolToSmiles(m)]=[mol,]
|
||||
except:
|
||||
print '--------------------------------'
|
||||
print 'could not process the molecule with the following name:'
|
||||
print mol.GetProp('_Name')
|
||||
|
||||
counter=0
|
||||
w=open('frames.smi','w')
|
||||
d=Chem.SDWriter('frames.sdf')
|
||||
for key,item in FrameDict.items():
|
||||
counter+=1
|
||||
#d=Chem.SDWriter(str(counter)+'.sdf')
|
||||
for i in item:
|
||||
i.SetProp('Scaffold',key)
|
||||
i.SetProp('Cluster',str(counter))
|
||||
d.write(i)
|
||||
print key,len(item)
|
||||
w.write(key+'\n')
|
||||
w.close
|
||||
print 'number of Frames found: %d' %(counter)
|
||||
49
Contrib/M_Kossner/README
Normal file
49
Contrib/M_Kossner/README
Normal file
@@ -0,0 +1,49 @@
|
||||
Contributions from Markus Kossner
|
||||
|
||||
Descriptions:
|
||||
|
||||
#-------------------------------
|
||||
Frames.py:
|
||||
|
||||
Basically what the code does is a walk from every Atom that is the
|
||||
neighbor of a ring away from that ring. If we can not reach another
|
||||
ring on the way, the atom chain will be deleted. However, as soon as
|
||||
we reach another ring, the chain will become a connecting chain in the
|
||||
scaffold. Ring Atoms [found by GetRingInfo()] as well as connecting
|
||||
non-ring chains are stored in a Chem.EditableMol-Object representing
|
||||
the Scaffold of the molecule.
|
||||
|
||||
There is a function, that can return this scaffold in two forms that
|
||||
differ in the interpretation of what a 'Scaffold' is:
|
||||
|
||||
- with mode='RedScaff' a Scaffold will be the pure molecular core
|
||||
ignoring bond or atom types! this is done by running over the
|
||||
Scaffold (...the editable mol from above) and changing any atom to
|
||||
carbon and any bond to a single bond
|
||||
|
||||
- with mode='Scaff' a Scaffold will be sensitive of element and bond
|
||||
type. With mode='Scaff' Cyclohexyl-, phenyl or pyridyl- mojeties
|
||||
will be different ring species. mode='RedScaff' will interpret them
|
||||
as six-membered rings and make all of them become a cyclohexane in
|
||||
the scaffold representation.
|
||||
|
||||
Usage of the script:
|
||||
- simply supply a .sdf file after the script name.
|
||||
- The program will generate a .sdf file called frames.sdf containing the
|
||||
cluster ID of the frame it belongs to as a property tag.
|
||||
- Additionally the raw frames are output to 'frames.smi'. This is a
|
||||
simple enumeration of the frames detected.
|
||||
|
||||
Please note, that the data is preliminary stored in memory. This
|
||||
means, that very large input files may cause the consumption of large
|
||||
amounts of memory at runtime!
|
||||
|
||||
#-------------------------------
|
||||
BaseFeatures_DIP2_NoMicrospecies.fdef
|
||||
|
||||
After I talked to Nik at the Sheffield Conference about the difficulty
|
||||
of defining Positive/Negative ionizable features by SMARTS he asked me
|
||||
to to send my approach towards the problem. Attached you will find
|
||||
the .fdef file I use. Hopefully there is something in there that might
|
||||
help in setting up robust feature definitions.
|
||||
|
||||
Reference in New Issue
Block a user