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# $Id$
#
# RDKit base fdef file.
# Created by Greg Landrum
#

AtomType NDonor [N&!H0&v3,N&!H0&+1&v4,n&H1&+0]
AtomType AmideN [$(N-C(=O))]
AtomType SulfonamideN [$([N;H0]S(=O)(=O))]
AtomType NDonor [$([Nv3](-C)(-C)-C)]

AtomType NDonor [$(n[n;H1]),$(nc[n;H1])]

AtomType ChalcDonor [O,S;H1;+0]
DefineFeature SingleAtomDonor [{NDonor},{ChalcDonor}]
  Family Donor
  Weights 1
EndFeature

# aromatic N, but not indole or pyrole or fusing two rings
AtomType NAcceptor [n;+0;!X3;!$([n;H1](cc)cc)]
AtomType NAcceptor [$([N;H0]#[C&v4])]
# tertiary nitrogen adjacent to aromatic carbon
AtomType NAcceptor [N&v3;H0;$(Nc)]

# removes thioether and nitro oxygen
AtomType ChalcAcceptor [O;H0;v2;!$(O=N-*)] 
Atomtype ChalcAcceptor [O;-;!$(*-N=O)] 

# Removed aromatic sulfur from ChalcAcceptor definition
Atomtype ChalcAcceptor [o;+0]

# Hydroxyls and acids
AtomType Hydroxyl [O;H1;v2]

# F is an acceptor so long as the C has no other halogen neighbors. This is maybe
# a bit too general, but the idea is to eliminate things like CF3
AtomType HalogenAcceptor [F;$(F-[#6]);!$(FC[F,Cl,Br,I])]

DefineFeature SingleAtomAcceptor [{Hydroxyl},{ChalcAcceptor},{NAcceptor},{HalogenAcceptor}]
  Family Acceptor
  Weights 1
EndFeature

# this one is delightfully easy:
DefineFeature AcidicGroup [C,S](=[O,S,P])-[O;H1,H0&-1]
  Family NegIonizable
  Weights 1.0,1.0,1.0
EndFeature

AtomType Carbon_NotDouble [C;!$(C=*)]
AtomType BasicNH2 [$([N;H2&+0][{Carbon_NotDouble}])]
AtomType BasicNH1 [$([N;H1&+0]([{Carbon_NotDouble}])[{Carbon_NotDouble}])]
AtomType PosNH3 [$([N;H3&+1][{Carbon_NotDouble}])]
AtomType PosNH2 [$([N;H2&+1]([{Carbon_NotDouble}])[{Carbon_NotDouble}])]
AtomType PosNH1 [$([N;H1&+1]([{Carbon_NotDouble}])([{Carbon_NotDouble}])[{Carbon_NotDouble}])]
AtomType BasicNH0 [$([N;H0&+0]([{Carbon_NotDouble}])([{Carbon_NotDouble}])[{Carbon_NotDouble}])]
AtomType QuatN [$([N;H0&+1]([{Carbon_NotDouble}])([{Carbon_NotDouble}])([{Carbon_NotDouble}])[{Carbon_NotDouble}])]


DefineFeature BasicGroup [{BasicNH2},{BasicNH1},{BasicNH0};!$(N[a])]
  Family PosIonizable
  Weights 1.0
EndFeature

# 14.11.2007 (GL): add !$([N+]-[O-]) constraint so we don't match
# nitro (or similar) groups
DefineFeature PosN [#7;+;!$([N+]-[O-])]
 Family PosIonizable
 Weights 1.0
EndFeature

# imidazole group can be positively charged (too promiscuous?)
DefineFeature Imidazole c1ncnc1
  Family PosIonizable
  Weights 1.0,1.0,1.0,1.0,1.0
EndFeature
# guanidine group is positively charged (too promiscuous?)
DefineFeature Guanidine NC(=N)N
  Family PosIonizable
  Weights 1.0,1.0,1.0,1.0
EndFeature

# the LigZn binder features were adapted from combichem.fdl
DefineFeature ZnBinder1 [S;D1]-[#6]
  Family ZnBinder
  Weights 1,0
EndFeature
DefineFeature ZnBinder2 [#6]-C(=O)-C-[S;D1]
  Family ZnBinder
  Weights 0,0,1,0,1
EndFeature
DefineFeature ZnBinder3 [#6]-C(=O)-C-C-[S;D1]
  Family ZnBinder
  Weights 0,0,1,0,0,1
EndFeature

DefineFeature ZnBinder4 [#6]-C(=O)-N-[O;D1]
  Family ZnBinder
  Weights 0,0,1,0,1
EndFeature
DefineFeature ZnBinder5 [#6]-C(=O)-[O;D1]
  Family ZnBinder
  Weights 0,0,1,1
EndFeature
DefineFeature ZnBinder6 [#6]-P(=O)(-O)-[C,O,N]-[C,H]
  Family ZnBinder
  Weights 0,0,1,1,0,0
EndFeature


# aromatic rings of various sizes:
#
# Note that with the aromatics, it's important to include the ring-size queries along with
# the aromaticity query for two reasons:
#   1) Much of the current feature-location code assumes that the feature point is 
#      equidistant from the atoms defining it. Larger definitions like: a1aaaaaaaa1 will actually 
#      match things like 'o1c2cccc2ccc1', which have an aromatic unit spread across multiple simple
#      rings and so don't fit that requirement.
#   2) It's *way* faster.
#

#
# 21.1.2008 (GL): update ring membership tests to reflect corrected meaning of
# "r" in SMARTS parser
#
AtomType AromR4 [a;r4,!R1&r3]
DefineFeature Arom4 [{AromR4}]1:[{AromR4}]:[{AromR4}]:[{AromR4}]:1
 Family Aromatic
 Weights 1.0,1.0,1.0,1.0
EndFeature
AtomType AromR5 [a;r5,!R1&r4,!R1&r3]
DefineFeature Arom5 [{AromR5}]1:[{AromR5}]:[{AromR5}]:[{AromR5}]:[{AromR5}]:1
 Family Aromatic
 Weights 1.0,1.0,1.0,1.0,1.0
EndFeature
AtomType AromR6 [a;r6,!R1&r5,!R1&r4,!R1&r3]
DefineFeature Arom6 [{AromR6}]1:[{AromR6}]:[{AromR6}]:[{AromR6}]:[{AromR6}]:[{AromR6}]:1
 Family Aromatic
 Weights 1.0,1.0,1.0,1.0,1.0,1.0
EndFeature
AtomType AromR7 [a;r7,!R1&r6,!R1&r5,!R1&r4,!R1&r3]
DefineFeature Arom7 [{AromR7}]1:[{AromR7}]:[{AromR7}]:[{AromR7}]:[{AromR7}]:[{AromR7}]:[{AromR7}]:1
 Family Aromatic
 Weights 1.0,1.0,1.0,1.0,1.0,1.0,1.0
EndFeature
AtomType AromR8 [a;r8,!R1&r7,!R1&r6,!R1&r5,!R1&r4,!R1&r3]
DefineFeature Arom8 [{AromR8}]1:[{AromR8}]:[{AromR8}]:[{AromR8}]:[{AromR8}]:[{AromR8}]:[{AromR8}]:[{AromR8}]:1
 Family Aromatic
 Weights 1.0,1.0,1.0,1.0,1.0,1.0,1.0,1.0
EndFeature

# hydrophobic features
# any carbon that is not bonded to a polar atom is considered a hydrophobe
# 
# 23.11.2007 (GL): match any bond (not just single bonds); add #6 at
#  beginning to make it more efficient
AtomType Carbon_Polar [#6;$([#6]~[#7,#8,#9])]
# 23.11.2007 (GL): don't match charged carbon
AtomType Carbon_NonPolar [#6;+0;!{Carbon_Polar}]

DefineFeature ThreeWayAttach [D3,D4;{Carbon_NonPolar}]
  Family Hydrophobe
  Weights 1.0
EndFeature

DefineFeature ChainTwoWayAttach [R0;D2;{Carbon_NonPolar}]
  Family Hydrophobe
  Weights 1.0
EndFeature

# hydrophobic atom
AtomType Hphobe [c,s,S&H0&v2,Br,I,{Carbon_NonPolar}]
AtomType RingHphobe [R;{Hphobe}]

# nitro groups in the RD code are always: *-[N+](=O)[O-]
DefineFeature Nitro2 [N;D3;+](=O)[O-]
  Family LumpedHydrophobe
  Weights 1.0,1.0,1.0
EndFeature

#
# 21.1.2008 (GL): update ring membership tests to reflect corrected meaning of
# "r" in SMARTS parser
#
AtomType Ring6 [r6,!R1&r5,!R1&r4,!R1&r3]
DefineFeature RH6_6 [{Ring6};{RingHphobe}]1[{Ring6};{RingHphobe}][{Ring6};{RingHphobe}][{Ring6};{RingHphobe}][{Ring6};{RingHphobe}][{Ring6};{RingHphobe}]1
  Family LumpedHydrophobe
  Weights 1.0,1.0,1.0,1.0,1.0,1.0
EndFeature

AtomType Ring5 [r5,!R1&r4,!R1&r3]
DefineFeature RH5_5 [{Ring5};{RingHphobe}]1[{Ring5};{RingHphobe}][{Ring5};{RingHphobe}][{Ring5};{RingHphobe}][{Ring5};{RingHphobe}]1
  Family LumpedHydrophobe
  Weights 1.0,1.0,1.0,1.0,1.0
EndFeature

AtomType Ring4 [r4,!R1&r3]
DefineFeature RH4_4 [{Ring4};{RingHphobe}]1[{Ring4};{RingHphobe}][{Ring4};{RingHphobe}][{Ring4};{RingHphobe}]1
  Family LumpedHydrophobe
  Weights 1.0,1.0,1.0,1.0
EndFeature

AtomType Ring3 [r3]
DefineFeature RH3_3 [{Ring3};{RingHphobe}]1[{Ring3};{RingHphobe}][{Ring3};{RingHphobe}]1
  Family LumpedHydrophobe
  Weights 1.0,1.0,1.0
EndFeature

DefineFeature tButyl [C;!R](-[CH3])(-[CH3])-[CH3]
  Family LumpedHydrophobe
  Weights 1.0,0.0,0.0,0.0
EndFeature

DefineFeature iPropyl [CH;!R](-[CH3])-[CH3]
  Family LumpedHydrophobe
  Weights 1.0,1.0,1.0
EndFeature