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//! MACCS 166-bit structural keys fingerprint.
//!
//! Bit i (0-indexed) corresponds to MACCS key (i+1).
//! SMARTS patterns match the official RDKit MACCSkeys.py definitions.
//!
//! Three keys use code-only logic (no SMARTS pattern):
//! - Key 1 (index 0): any isotopically-labelled atom
//! - Key 125 (index 124): aromatic ring count > 1
//! - Key 166 (index 165): fragment count > 1 (disconnected molecule)
//!
//! For count-based keys the second tuple element is the minimum count:
//! the bit is set when `matches.len() > min_count`.
use chematic_core::Molecule;
use chematic_perception::find_sssr;
use chematic_smarts::{find_matches, parse_smarts};
use crate::bitvec::BitVec2048;
/// `(smarts, min_count)` pairs for all 166 MACCS keys (index = key - 1).
/// Empty string or "?" → special-case key handled in `maccs()`.
static MACCS_SMARTS: &[(&str, usize)] = &[
("?", 0), // key 1 - ISOTOPE (special)
("[#104]", 0), // key 2 - Atomic num >103
("[#32,#33,#34,#50,#51,#52,#82,#83,#84]", 0), // key 3 - Group IVa,Va,VIa
("[Ac,Th,Pa,U,Np,Pu,Am,Cm,Bk,Cf,Es,Fm,Md,No,Lr]", 0), // key 4 - Actinide
("[Sc,Ti,Y,Zr,Hf]", 0), // key 5 - Group IIIB,IVB
("[La,Ce,Pr,Nd,Pm,Sm,Eu,Gd,Tb,Dy,Ho,Er,Tm,Yb,Lu]", 0), // key 6 - Lanthanide
("[V,Cr,Mn,Nb,Mo,Tc,Ta,W,Re]", 0), // key 7 - Group VB,VIB,VIIB
("[!#6;!#1]1~*~*~*~1", 0), // key 8 - 4M heterocycle
("[Fe,Co,Ni,Ru,Rh,Pd,Os,Ir,Pt]", 0), // key 9 - Group VIII
("[Be,Mg,Ca,Sr,Ba,Ra]", 0), // key 10 - Group IIa
("*1~*~*~*~1", 0), // key 11 - 4M ring
("[Cu,Zn,Ag,Cd,Au,Hg]", 0), // key 12 - Group IB,IIB
("[#8]~[#7](~[#6])~[#6]", 0), // key 13 - ON(C)C
("[#16]-[#16]", 0), // key 14 - S-S
("[#8]~[#6](~[#8])~[#8]", 0), // key 15 - OC(O)O
("[!#6;!#1]1~*~*~1", 0), // key 16 - 3M heterocycle
("[#6]#[#6]", 0), // key 17 - alkyne
("[#5,#13,#31,#49,#81]", 0), // key 18 - Group IIIA
("*1~*~*~*~*~*~*~1", 0), // key 19 - 7M ring
("[#14]", 0), // key 20 - Si
("[#6]=[#6](~[!#6;!#1])~[!#6;!#1]", 0), // key 21 - C=C(Q)Q
("*1~*~*~1", 0), // key 22 - 3M ring
("[#7]~[#6](~[#8])~[#8]", 0), // key 23 - NC(O)O
("[#7]-[#8]", 0), // key 24 - N-O
("[#7]~[#6](~[#7])~[#7]", 0), // key 25 - NC(N)N
("[#6;R]=[#6;R]", 0), // key 26 - ring C=C (was =;@ which fails to parse)
("[I]", 0), // key 27 - I
("[!#6;!#1]~[CH2]~[!#6;!#1]", 0), // key 28 - QCH2Q
("[#15]", 0), // key 29 - P
("[#6]~[!#6;!#1](~[#6])(~[#6])~*", 0), // key 30 - CQ(C)(C)A
("[!#6;!#1]~[F,Cl,Br,I]", 0), // key 31 - QX
("[#6]~[#16]~[#7]", 0), // key 32 - CSN
("[#7]~[#16]", 0), // key 33 - NS
("[CH2]=*", 0), // key 34 - CH2=A
("[Li,Na,K,Rb,Cs,Fr]", 0), // key 35 - Alkali metal
("[#16R]", 0), // key 36 - S heterocycle
("[#7]~[#6](~[#8])~[#7]", 0), // key 37 - NC(O)N
("[#7]~[#6](~[#6])~[#7]", 0), // key 38 - NC(C)N
("[#8]~[#16](~[#8])~[#8]", 0), // key 39 - OS(O)O
("[#16]-[#8]", 0), // key 40 - S-O
("[#6]#[#7]", 0), // key 41 - nitrile
("F", 0), // key 42 - F
("[!#6;!#1;!H0]~*~[!#6;!#1;!H0]", 0), // key 43 - QHAQH
("[!#1;!#6;!#7;!#8;!#9;!#14;!#15;!#16;!#17;!#35;!#53]", 0), // key 44 - OTHER
("[#6]=[#6]~[#7]", 0), // key 45 - C=CN
("Br", 0), // key 46 - Br
("[#16]~*~[#7]", 0), // key 47 - SAN
("[#8]~[!#6;!#1](~[#8])(~[#8])", 0), // key 48 - OQ(O)O
("[!+0]", 0), // key 49 - charged atom
("[#6]=[#6](~[#6])~[#6]", 0), // key 50 - C=C(C)C
("[#6]~[#16]~[#8]", 0), // key 51 - CSO
("[#7]~[#7]", 0), // key 52 - N-N
("[!#6;!#1;!H0]~*~*~*~[!#6;!#1;!H0]", 0), // key 53 - QHAAAQH
("[!#6;!#1;!H0]~*~*~[!#6;!#1;!H0]", 0), // key 54 - QHAAQH
("[#8]~[#16]~[#8]", 0), // key 55 - OSO
("[#8]~[#7](~[#8])~[#6]", 0), // key 56 - ON(O)C
("[#8R]", 0), // key 57 - O heterocycle
("[!#6;!#1]~[#16]~[!#6;!#1]", 0), // key 58 - QSQ
("[#16]!:*:*", 0), // key 59 - S-nonarom-arom chain
("[#16]=[#8]", 0), // key 60 - S=O
("*~[#16](~*)~*", 0), // key 61 - AS(A)A
("*@*!@*@*", 0), // key 62 - ring-open-ring
("[#7]=[#8]", 0), // key 63 - N=O
("*@*!@[#16]", 0), // key 64 - ring-open-S
("c:n", 0), // key 65 - aromatic C-N
("[#6]~[#6](~[#6])(~[#6])~*", 0), // key 66 - quaternary C
("[!#6;!#1]~[#16]", 0), // key 67 - QS
("[!#6;!#1;!H0]~[!#6;!#1;!H0]", 0), // key 68 - QHQH
("[!#6;!#1]~[!#6;!#1;!H0]", 0), // key 69 - QQH
("[!#6;!#1]~[#7]~[!#6;!#1]", 0), // key 70 - QNQ
("[#7]~[#8]", 0), // key 71 - N-O (any bond)
("[#8]~*~*~[#8]", 0), // key 72 - O..O (2 bonds)
("[#16]=*", 0), // key 73 - S=A
("[CH3]~*~[CH3]", 0), // key 74 - CH3-A-CH3
("*!@[#7]@*", 0), // key 75 - open-N-ring
("[#6]=[#6](~*)~*", 0), // key 76 - C=C(A)A
("[#7]~*~[#7]", 0), // key 77 - N-A-N
("[#6]=[#7]", 0), // key 78 - C=N
("[#7]~*~*~[#7]", 0), // key 79 - N-A-A-N
("[#7]~*~*~*~[#7]", 0), // key 80 - N-A-A-A-N
("[#16]~*(~*)~*", 0), // key 81 - S(A)A
("*~[CH2]~[!#6;!#1;!H0]", 0), // key 82 - A-CH2-QH
("[!#6;!#1]1~*~*~*~*~1", 0), // key 83 - 5M heterocycle
("[NH2]", 0), // key 84 - NH2
("[#6]~[#7](~[#6])~[#6]", 0), // key 85 - tertiary N
("[C;H2,H3][!#6;!#1][C;H2,H3]", 0), // key 86 - CH2/CH3 Q CH2/CH3
("[F,Cl,Br,I]!@*@*", 0), // key 87 - X-open-ring
("[#16]", 0), // key 88 - any S
("[#8]~*~*~*~[#8]", 0), // key 89 - O..O (3 bonds)
("[$([!#6;!#1;!H0]~*~*~[CH2]~*),$([!#6;!#1;!H0;R]1@[R]@[R]@[CH2;R]1),$([!#6;!#1;!H0]~[R]1@[R]@[CH2;R]1)]", 0), // key 90
("[$([!#6;!#1;!H0]~*~*~*~[CH2]~*),$([!#6;!#1;!H0;R]1@[R]@[R]@[R]@[CH2;R]1),$([!#6;!#1;!H0]~[R]1@[R]@[R]@[CH2;R]1),$([!#6;!#1;!H0]~*~[R]1@[R]@[CH2;R]1)]", 0), // key 91
("[#8]~[#6](~[#7])~[#6]", 0), // key 92 - OC(N)C
("[!#6;!#1]~[CH3]", 0), // key 93 - Q-CH3
("[!#6;!#1]~[#7]", 0), // key 94 - Q-N
("[#7]~*~*~[#8]", 0), // key 95 - N-A-A-O
("*1~*~*~*~*~1", 0), // key 96 - 5M ring
("[#7]~*~*~*~[#8]", 0), // key 97 - N-A-A-A-O
("[!#6;!#1]1~*~*~*~*~*~1", 0), // key 98 - 6M heterocycle
("[#6]=[#6]", 0), // key 99 - C=C
("*~[CH2]~[#7]", 0), // key 100 - A-CH2-N
("[$([R]@1@[R]@[R]@[R]@[R]@[R]@[R]@[R]1),$([R]@1@[R]@[R]@[R]@[R]@[R]@[R]@[R]@[R]1),$([R]@1@[R]@[R]@[R]@[R]@[R]@[R]@[R]@[R]@[R]1),$([R]@1@[R]@[R]@[R]@[R]@[R]@[R]@[R]@[R]@[R]@[R]1),$([R]@1@[R]@[R]@[R]@[R]@[R]@[R]@[R]@[R]@[R]@[R]@[R]1),$([R]@1@[R]@[R]@[R]@[R]@[R]@[R]@[R]@[R]@[R]@[R]@[R]@[R]1)]", 0), // key 101 - 8-14M ring
("[!#6;!#1]~[#8]", 0), // key 102 - Q-O
("Cl", 0), // key 103 - Cl
("[!#6;!#1;!H0]~*~[CH2]~*", 0), // key 104 - QH-A-CH2-A
("*@*(@*)@*", 0), // key 105 - ring branch
("[!#6;!#1]~*(~[!#6;!#1])~[!#6;!#1]", 0), // key 106 - QA(Q)Q
("[F,Cl,Br,I]~*(~*)~*", 0), // key 107 - X-A(A)A
("[CH3]~*~*~*~[CH2]~*", 0), // key 108 - CH3-A-A-A-CH2-A
("*~[CH2]~[#8]", 0), // key 109 - A-CH2-O
("[#7]~[#6]~[#8]", 0), // key 110 - NCO
("[#7]~*~[CH2]~*", 0), // key 111 - N-A-CH2-A
("*~*(~*)(~*)~*", 0), // key 112 - branched atom
("[#8]!:*:*", 0), // key 113 - O-nonarom-arom
("[CH3]~[CH2]~*", 0), // key 114 - CH3-CH2-A
("[CH3]~*~[CH2]~*", 0), // key 115 - CH3-A-CH2-A
("[$([CH3]~*~*~[CH2]~*),$([CH3]~*1~*~[CH2]1)]", 0), // key 116 - CH3-A-A-CH2
("[#7]~*~[#8]", 0), // key 117 - N-A-O
("[$(*~[CH2]~[CH2]~*),$(*1~[CH2]~[CH2]1)]", 1), // key 118 - ACH2CH2A > 1
("[#7]=*", 0), // key 119 - N=A
("[!#6;R]", 1), // key 120 - het in ring > 1
("[#7;R]", 0), // key 121 - N heterocycle
("*~[#7](~*)~*", 0), // key 122 - AN(A)A
("[#8]~[#6]~[#8]", 0), // key 123 - OCO
("[!#6;!#1]~[!#6;!#1]", 0), // key 124 - QQ
("?", 0), // key 125 - aromatic ring > 1 (special)
("*!@[#8]!@*", 0), // key 126 - A-open-O-open-A
("*@*!@[#8]", 1), // key 127 - ring-open-O > 1
("[$(*~[CH2]~*~*~*~[CH2]~*),$([R]1@[CH2;R]@[R]@[R]@[R]@[CH2;R]1),$(*~[CH2]~[R]1@[R]@[R]@[CH2;R]1),$(*~[CH2]~*~[R]1@[R]@[CH2;R]1)]", 0), // key 128
("[$(*~[CH2]~*~*~[CH2]~*),$([R]1@[CH2;R]@[R]@[R]@[CH2;R]1),$(*~[CH2]~[R]1@[R]@[CH2;R]1),$(*~[CH2]~*1~*~[CH2]1)]", 0), // key 129
("[!#6;!#1]~[!#6;!#1]", 1), // key 130 - QQ > 1
("[!#6;!#1;!H0]", 1), // key 131 - QH > 1
("[#8]~*~[CH2]~*", 0), // key 132 - O-A-CH2-A
("*@*!@[#7]", 0), // key 133 - ring-open-N
("[F,Cl,Br,I]", 0), // key 134 - halogen
("[#7]!:*:*", 0), // key 135 - N-nonarom-arom
("[#8]=*", 1), // key 136 - O=A > 1
("[!C;!c;R]", 0), // key 137 - non-C in ring
("[!#6;!#1]~[CH2]~*", 1), // key 138 - QCH2A > 1
("[O;!H0]", 0), // key 139 - OH
("[#8]", 3), // key 140 - O > 3
("[CH3]", 2), // key 141 - CH3 > 2
("[#7]", 1), // key 142 - N > 1
("*@*!@[#8]", 0), // key 143 - ring-open-O
("*!:*:*!:*", 0), // key 144 - nonarom-arom-nonarom
("*1~*~*~*~*~*~1", 1), // key 145 - 6M ring > 1
("[#8]", 2), // key 146 - O > 2
("[$(*~[CH2]~[CH2]~*),$([R]1@[CH2;R]@[CH2;R]1)]", 0), // key 147 - ACH2CH2A
("*~[!#6;!#1](~*)~*", 0), // key 148 - AQ(A)A
("[C;H3,H4]", 1), // key 149 - CH3 > 1
("*!@*@*!@*", 0), // key 150 - open-ring-open
("[#7;!H0]", 0), // key 151 - NH
("[#8]~[#6](~[#6])~[#6]", 0), // key 152 - OC(C)C
("[!#6;!#1]~[CH2]~*", 0), // key 153 - QCH2A
("[#6]=[#8]", 0), // key 154 - C=O
("*!@[CH2]!@*", 0), // key 155 - open-CH2-open
("[#7]~*(~*)~*", 0), // key 156 - NA(A)A
("[#6]-[#8]", 0), // key 157 - C-O
("[#6]-[#7]", 0), // key 158 - C-N
("[#8]", 1), // key 159 - O > 1
("[C;H3,H4]", 0), // key 160 - CH3
("[#7]", 0), // key 161 - N
("[a]", 0), // key 162 - aromatic atom
("*1~*~*~*~*~*~1", 0), // key 163 - 6M ring
("[#8]", 0), // key 164 - O
("[R]", 0), // key 165 - ring atom
("?", 0), // key 166 - fragments > 1 (special)
];
fn count_aromatic_rings(mol: &Molecule) -> usize {
find_sssr(mol)
.rings()
.iter()
.filter(|ring| ring.iter().all(|&idx| mol.atom(idx).aromatic))
.count()
}
/// Compute the MACCS 166-bit structural keys fingerprint for `mol`.
///
/// Bit `i` (0-indexed) corresponds to MACCS key `i+1`. Keys 1, 125, and 166
/// use code-only logic; all other keys use SMARTS matching.
/// For count-based keys (14 total), the bit is set only when the match count
/// exceeds the threshold stored in `MACCS_SMARTS`.
pub fn maccs(mol: &Molecule) -> BitVec2048 {
let mut fp = BitVec2048::new();
for (i, &(pattern, min_count)) in MACCS_SMARTS.iter().enumerate() {
if pattern == "?" || pattern.is_empty() {
continue;
}
if let Ok(query) = parse_smarts(pattern)
&& find_matches(&query, mol).len() > min_count
{
fp.set(i);
}
// Patterns that fail to parse silently leave the bit unset.
}
// Key 1 (index 0): isotope — any atom carrying an explicit mass label
if mol.atoms().any(|(_, a)| a.isotope.is_some()) {
fp.set(0);
}
// Key 125 (index 124): aromatic ring count > 1
if count_aromatic_rings(mol) > 1 {
fp.set(124);
}
// Key 166 (index 165): fragment count > 1 (disconnected molecule)
if !mol.is_connected() {
fp.set(165);
}
fp
}
#[cfg(test)]
mod tests {
use super::*;
use chematic_smiles::parse;
#[test]
fn maccs_benzene_has_aromatic_bits() {
let mol = parse("c1ccccc1").unwrap();
let fp = maccs(&mol);
assert!(fp.get(161), "key 162 (any aromatic atom) should be set for benzene");
assert!(fp.get(162), "key 163 (6M ring) should be set for benzene");
assert!(fp.get(164), "key 165 (ring atom) should be set for benzene");
}
#[test]
fn maccs_benzene_aromatic_ring_gt1_not_set() {
// Benzene has exactly 1 aromatic ring → key 125 should NOT be set
let mol = parse("c1ccccc1").unwrap();
let fp = maccs(&mol);
assert!(!fp.get(124), "benzene has only 1 aromatic ring; key 125 must be 0");
}
#[test]
fn maccs_naphthalene_aromatic_ring_gt1_set() {
// Naphthalene has 2 aromatic rings → key 125 should be set
let mol = parse("c1ccc2ccccc2c1").unwrap();
let fp = maccs(&mol);
assert!(fp.get(124), "naphthalene has 2 aromatic rings; key 125 must be 1");
}
#[test]
fn maccs_ethanol_has_oxygen_bits() {
let mol = parse("CCO").unwrap();
let fp = maccs(&mol);
assert!(fp.get(163), "key 164 (O) should be set for ethanol");
assert!(fp.get(156), "key 157 (C-O) should be set for ethanol");
assert!(fp.get(138), "key 139 (OH) should be set for ethanol");
}
#[test]
fn maccs_isotope_key() {
// [13C] has an isotope label → key 1 should be set
let labeled = parse("[13CH4]").unwrap();
let unlabeled = parse("C").unwrap();
assert!(maccs(&labeled).get(0), "key 1 should be set for [13C]");
assert!(!maccs(&unlabeled).get(0), "key 1 should not be set for CH4");
}
#[test]
fn maccs_fragment_key() {
// NaCl ([Na+].[Cl-]) is disconnected → key 166 should be set
let salt = parse("[Na+].[Cl-]").unwrap();
let ethanol = parse("CCO").unwrap();
assert!(maccs(&salt).get(165), "key 166 should be set for [Na+].[Cl-]");
assert!(!maccs(ðanol).get(165), "key 166 should not be set for CCO");
}
#[test]
fn maccs_oxygen_count_keys() {
// Citric acid has 6 O → keys 159/146/140 (O>1, O>2, O>3) should be set
let citric = parse("OC(CC(O)(C(=O)O)C(=O)O)(C(=O)O)").unwrap();
let fp = maccs(&citric);
assert!(fp.get(158), "key 159 (O>1) should be set for citric acid");
assert!(fp.get(145), "key 146 (O>2) should be set for citric acid");
assert!(fp.get(139), "key 140 (O>3) should be set for citric acid");
}
#[test]
fn maccs_nitrile_key() {
let mol = parse("CC#N").unwrap();
let fp = maccs(&mol);
assert!(fp.get(40), "key 41 (C#N nitrile) should be set for acetonitrile");
}
#[test]
fn maccs_bromine_key() {
let mol = parse("c1ccccc1Br").unwrap();
let fp = maccs(&mol);
assert!(fp.get(45), "key 46 (Br) should be set for bromobenzene");
}
#[test]
fn maccs_carbonyl_key() {
let mol = parse("CC(=O)Oc1ccccc1C(=O)O").unwrap();
let fp = maccs(&mol);
assert!(fp.get(153), "key 154 (C=O) should be set for aspirin");
}
#[test]
fn maccs_deterministic() {
let mol = parse("c1ccccc1").unwrap();
assert_eq!(maccs(&mol), maccs(&mol));
}
#[test]
fn maccs_n_gt1_key() {
// Ethylenediamine has 2 N → key 142 (N>1) should be set
let mol = parse("NCCN").unwrap();
let fp = maccs(&mol);
assert!(fp.get(141), "key 142 (N>1) should be set for ethylenediamine");
}
#[test]
fn maccs_key26_ring_double_bond() {
// Cyclohexene has a ring C=C → key 26 (index 25) should be set
let mol = parse("C1=CCCCC1").unwrap();
assert!(maccs(&mol).get(25), "cyclohexene should set key 26 (ring C=C)");
// Ethylene has C=C but not in ring → key 26 should NOT be set
let mol2 = parse("C=C").unwrap();
assert!(!maccs(&mol2).get(25), "ethylene: key 26 (ring C=C) should be 0");
}
#[test]
fn all_maccs_smarts_parse() {
let mut failed = Vec::new();
for (i, &(pattern, _)) in MACCS_SMARTS.iter().enumerate() {
if pattern == "?" || pattern.is_empty() {
continue;
}
if parse_smarts(pattern).is_err() {
failed.push((i + 1, pattern));
}
}
assert!(
failed.is_empty(),
"MACCS SMARTS parse failures: {:?}",
failed
);
}
}