# $Id$
#
# 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}]
  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))   !$([n;H1](cc)cc)
# tertiary nitrogen adjacent to aromatic carbon
AtomType NAcceptor [N&v3;H0;$(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
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 NOT delightfully easy :-) 
#We wil define some additional NegIonizable Features 
#I later found some similar substructures in 
# Good,Oprea J.Comput.Aided.Mol.Des (2008) 22:169-178:

DefineFeature AcidicGroup [C,S,P](=[O,S])-[O;H1,H0&-1]
  Family NegIonizable
  Weights 1.0,1.0,1.0
EndFeature

DefineFeature AcidicN [{AcidicN};!$([nH,n-1]1cnnn1)]
  Family NegIonizable
  Weights 1
EndFeature

DefineFeature Tetrazole c1nnn[nH,n-1]1
  Family NegIonizable
  Weights 1,1,1,1,1
EndFeature

AtomType Carbon_NotDouble [C;!$(C=*)]
AtomType BasicNH2 [$([N;H2&+0;!R][{Carbon_NotDouble}])]
AtomType BasicNH1 [$([N;H1&+0;!R]([{Carbon_NotDouble}])[{Carbon_NotDouble}])]
AtomType BasicNH0 [$([N;H0&+0;!R]([{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

#Define electronegative atoms that might have an impact on pka of moieties otherwise basic?
AtomType ElectroNegative [N,n,O,o,F,Cl,Br]
# imidazole group can be positively charged (too promiscuous?)
#DefineFeature Imidazole  [n,+0]1[$(cC),$([cH])][n;+0][$(cC),$([cH])][$(cC),$([cH])]1
#  Family PosIonizable
#  Weights 1.0,1.0,1.0,1.0,1.0
#EndFeature

# guanidine group is positively charged (too promiscuous? We do not match any aromatic systems here. That would be too promiscuous!)
DefineFeature Guanidine [N;+0;!{AmideN}][#6;+0](=[N;+0;!{AmideN}])[N;+0;!{AmideN}]
  Family PosIonizable
  Weights 1.0,1.0,1.0,1.0
EndFeature

# amidine group is positively charged (too promiscuous?)
DefineFeature Amidine [N;+0;!{AmideN}][#6]=,:[#7;+0;!$(ncn);!{AmideN}]
  Family PosIonizable
  Weights 1.0,1.0,1.0
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}]

# 6.2009 (MK): aromatic c is not per se a hydrophobic atom
#AtomType RingHphobe [R;{Hphobe}]
AtomType Hphobe [s,S&H0&v2,Br,I,Cl,F,{Carbon_NonPolar}]

# 8.2009 (MK): update  'Hydrophobes'
DefineFeature Hphobe [{Hphobe}{Hphobe}]
 Family Hydrophobe
  Weights 1.0
EndFeature

# 8.2009 (MK): 
DefineFeature Methyl [CH3]
  Family Hydrophobe
  Weights 1.0
EndFeature

# 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

DefineFeature ThreeWayAttach [D3,D4]
  Family LumpedHydrophobe
  Weights 1.0
EndFeature

DefineFeature ChainEnd [R0;D1][R0;D2]
  Family LumpedHydrophobe
  Weights 1.0,1.0
EndFeature

# 5.2009 (MK): update ring membership tests to reflect 'Lumped Hydrophobes' 
AtomType Ring6 [r6,!R1&r5,!R1&r4,!R1&r3]
DefineFeature R6_6 [{Ring6}]1[{Ring6}][{Ring6}][{Ring6}][{Ring6}][{Ring6}]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 R5_5 [{Ring5}]1[{Ring5}][{Ring5}][{Ring5}][{Ring5}]1
  Family LumpedHydrophobe
  Weights 1.0,1.0,1.0,1.0,1.0
EndFeature
AtomType Ring4 [r4,!R1&r3]
DefineFeature H4_4 [{Ring4}]1[{Ring4}][{Ring4}][{Ring4}]1
  Family LumpedHydrophobe
  Weights 1.0,1.0,1.0,1.0
EndFeature
AtomType Ring3 [r3]
DefineFeature R3_3 [{Ring3}]1[{Ring3}][{Ring3}]1
  Family LumpedHydrophobe
  Weights 1.0,1.0,1.0
EndFeature