1.What is MACCS keys？
The MACCS (Molecular ACCess System) keys [1,2] are one of the most commonly used structural keys. They are sometimes referred to as the MDL keys, named after the company that developed them [the MDL Information Systems (now BIOVIA)]. While there are two sets of MACCS keys (one with 960 keys and the other containing a subset of 166 keys), only the shorter fragment definitions are available to the public. These 166 public keys are implemented in popular open-source cheminformatics software packages, including RDKit [3], OpenBabel [4,5], CDK [6,7], etc.
2.What is the exact meaning of each bit？
The fragment definitions for the MACCS 166 keys can be found in this document:
rdkit/MACCSkeys.py at master · rdkit/rdkit · GitHub
Additionally，MACCS is developed based on SMART which is a language for describing molecular patterns, owing to this, the official document is adhered below in which the meaning of every symbol in SMARTS sequence is detailed.
Daylight Theory: SMARTS - A Language for Describing Molecular Patterns
The exact definition of the MACCS 166 keys is displayed in the chart below：
To understand the remark better, it is recomemded that following extra note the reader should acknowlege:
1.Q in chart means non-carbon group or atom
2.A means any group or atom
3.Some chemical sub-structure graphs are provided as example to explain the SAMRTS code more vividly.
| S.N | SMARTS CODE | REMARK | CHINESE REMARK |
|---|---|---|---|
| 1 | ('?', 0) | ISOTOPE | 有无同位素 |
| 2 | ('[#104]', 0) | limit the above def'n since the RDKit only accepts up to #104 | 目前RDKIT元素类型只更新到103号 |
| 3 | ('[#32,#33,#34,#50,#51,#52,#82,#83,#84]', 0) | IVa,Va,VIa Rows 4-6 | 4-6周期 14-16族元素，包含锗、砷、硒、锡、锑(tī)、碲、 铊、铅、铋 |
| 4 | ('[Ac,Th,Pa,U,Np,Pu,Am,Cm,Bk,Cf,Es,Fm,Md,No,Lr]', 0) | Actinide | 锕系元素 |
| 5 | ('[Sc,Ti,Y,Zr,Hf]', 0) | Group IIIB,IVB | 4-6 周期 鈧族 鈦族元素 |
| 6 | ('[La,Ce,Pr,Nd,Pm,Sm,Eu,Gd,Tb,Dy,Ho,Er,Tm,Yb,Lu]', 0) | Lanthanide | 镧系元素 |
| 7 | ('[V,Cr,Mn,Nb,Mo,Tc,Ta,W,Re]', 0) | Group VB,VIB,VIIB | 4-6周期 钒族、铬族、锰族元素 |
| 8 | ('[!#6;!#1]1~*~*~*~1', 0) | QAAA@1 | 非碳元非氢元4元环，任意键 |
| 9 | ('[Fe,Co,Ni,Ru,Rh,Pd,Os,Ir,Pt]', 0) | Group VIII | 4-6周期，铁族、钴族、镍族元素 |
| 10 | ('[Be,Mg,Ca,Sr,Ba,Ra]', 0) | Group IIa (Alkaline earth) | 碱土 |
| 11 | ('*1~*~*~*~1', 0) | 4M Ring | 通配4元环，任意键，任意元素 |
| 12 | ('[Cu,Zn,Ag,Cd,Au,Hg]', 0) | Group IB,IIB | 4-6周期，铜族、锌族元素 |
| 13 | ('[#8]~[#7](~[#6])~[#6]', 0) | ON(C)C |  |
| 14 | ('[#16]-[#16]', 0) | S-S | 硫单键 |
| 15 | ('[#8]~[#6](~[#8])~[#8]', 0) | OC(O)O |  |
| 16 | ('[!#6;!#1]1~*~*~1', 0) | QAA@1 | 非碳基 任意2基团 组成的逆时针三元环 |
| 17 | ('[#6]#[#6]', 0) | CTC | 双碳三键 |
| 18 | ('[#5,#13,#31,#49,#81]', 0) | Group IIIA | 除第7周期外的硼族元素 |
| 19 | ('*1~*~*~*~*~*~*~1', 0) | 7M Ring | 通配7元环，任意键，任意元素 |
| 20 | ('[#14]', 0) | Si | 硅元素 |
| 21 | ('[#6]=[#6](~[!#6;!#1])~[!#6;!#1]', 0) | C=C(Q)Q | 碳双键链接非碳非氢元素 |
| 22 | ('*1~*~*~1', 0) | 3M Ring | 3元环，任意元素，任意键 |
| 23 | ('[#7]~[#6](~[#8])~[#8]', 0) | NC(O)O |  |
| 24 | ('[#7]-[#8]', 0) | N-O | 氮、氧单键 |
| 25 | ('[#7]~[#6](~[#7])~[#7]', 0) | NC(N)N |  |
| 26 | ('[#6]=;@[#6](@*)@*', 0) | C$=C($A)$A | |
| 27 | ('[I]', 0) | I | 碘元素 |
| 28 | ('[!#6;!#1]~[CH2]~[!#6;!#1]', 0) | QCH2Q | 亚甲基与非碳连接 |
| 29 | ('[#15]', 0) | P | 磷元素 |
| 30 | ('[#6]~[!#6;!#1](~[#6])(~[#6])~*', 0) | CQ(C)(C)A | |
| 31 | ('[!#6;!#1]~[F,Cl,Br,I]', 0) | QX | 非碳基接卤素 |
| 32 | ('[#6]~[#16]~[#7]', 0) | CSN | 碳硫氮任意键连接 |
| 33 | ('[#7]~[#16]', 0) | NS | 氮硫任意键连接 |
| 34 | ('[CH2]=*', 0), | CH2=A | 亚甲基双键连接任意 |
| 35 | ('[Li,Na,K,Rb,Cs,Fr]', 0) | Group IA (Alkali Metal) | 碱金属族 |
| 36 | ('[#16R]', 0) | S Heterocycle | 硫环 |
| 37 | ('[#7]~[#6](~[#8])~[#7]', 0) | NC(O)N |  |
| 38 | ('[#7]~[#6](~[#6])~[#7]', 0) | NC(C)N |  |
| 39 | ('[#8]~[#16](~[#8])~[#8]', 0) | OS(O)O |  |
| 40 | ('[#16]-[#8]', 0) | S-O | 硫氧单键 |
| 41 | ('[#6]#[#7]', 0) | CTN | 碳氮三键 |
| 42 | ('F', 0) | F | 氟元素 |
| 43 | ('[!#6;!#1;!H0]~*~[!#6;!#1;!H0]', 0) | QHAQH |  |
| 44 | ('[!#1;!#6;!#7;!#8;!#9;!#14;!#15;!#16;!#17;!#35;!#53]', 0) | other | 有元素非碳、非氢、非氮、非氧、非硅、非磷、非卤素 |
| 45 | ('[#6]=[#6]~[#7]', 0) | C=CN | |
| 46 | ('Br', 0), | Br | 溴元素 |
| 47 | ('[#16]~*~[#7]', 0) | SAN | 硫+任意+氮 |
| 48 | ('[#8]~[!#6;!#1](~[#8])(~[#8])', 0) | OQ(O)O | |
| 49 | ('[!+0]', 0) | charge | 电子 |
| 50 | ('[#6]=[#6](~[#6])~[#6]', 0) | C=C(C)C | |
| 51 | ('[#6]~[#16]~[#8]', 0) | CSO | 碳硫氧任意键连接 |
| 52 | ('[#7]~[#7]', 0) | NN | 氮氮任意连接 |
| 53 | ('[!#6;!#1;!H0]~*~*~*~[!#6;!#1;!H0]', 0) | QHAAAQH | 非碳基团接任意3元素接非碳基团 |
| 54 | ('[!#6;!#1;!H0]~*~*~[!#6;!#1;!H0]', 0) | QHAAQH | 非碳基团接任意2元素接非碳基团 |
| 55 | ('[#8]~[#16]~[#8]', 0) | OSO | 氧硫氧任意键 |
| 57 | ('[#8R]', 0) | O Heterocycle | 氧环 |
| 58 | ('[!#6;!#1]~[#16]~[!#6;!#1]', 0) | QSQ | 非碳基接硫接非碳基 |
| 59 | ('[#16]!:*:*', 0) | Snot%A%A | %代表芳香键 |
| 60 | ('[#16]=[#8]', 0) | S=O | 硫氧双键 |
| 61 | ('*~[#16](~*)~*', 0) | AS(A)A | |
| 62 | ('*@*!@*@*', 0) | A$!A$A | |
| 63 | ('[#7]=[#8]', 0) | N=O | |
| 64 | ('*@*!@[#16]', 0) | A$A!S | |
| 65 | ('c:n', 0) | C%N | |
| 66 | ('[#6]~[#6](~[#6])(~[#6])~*', 0) | CC(C)(C)A | |
| 67 | ('[!#6;!#1]~[#16]', 0) | QS | |
| 68 | ('[!#6;!#1;!H0]~[!#6;!#1;!H0]', 0) | QHQH | |
| 69 | ('[!#6;!#1]~[!#6;!#1;!H0]', 0) | QH | |
| 70 | ('[!#6;!#1]~[#7]~[!#6;!#1]', 0) | QNQ | |
| 71 | ('[#7]~[#8]', 0) | NO | |
| 72 | ('[#8]~*~*~[#8]', 0) | OAAO | |
| 73 | ('[#16]=*', 0) | S=A | S双键连接任意原子 |
| 74 | ('[CH3]~*~[CH3]', 0) | CH3ACH3 | |
| 75 | ('*!@[#7]@*', 0) | A!N$A | |
| 76 | ('[#6]=[#6](~*)~*', 0) | C=C(A)A | |
| 77 | ('[#7]~*~[#7]', 0) | NAN | |
| 78 | ('[#6]=[#7]', 0) | C=N | |
| 79 | ('[#7]~*~*~[#7]', 0) | NAAN | |
| 80 | ('[#7]~*~*~*~[#7]', 0) | NAAAN | |
| 81 | ('[#16]~*(~*)~*', 0) | SA(A)A | |
| 82 | ('*~[CH2]~[!#6;!#1;!H0]', 0) | ACH2QH | |
| 83 | ('[!#6;!#1]1~*~*~*~*~1', 0) | QAAAA@1 | |
| 84 | ('[NH2]', 0) | NH2 | 氨基 |
| 85 | ('[#6]~[#7](~[#6])~[#6]', 0) | CN(C)C | |
| 86 | ('[C;H2,H3][!#6;!#1][C;H2,H3]', 0) | CH2QCH2 | |
| 87 | ('[F,Cl,Br,I]!@*@*', 0) | X!A$A | X代表卤素 |
| 88 | ('[#16]', 0) | S | 硫原子 |
| 89 | ('[#8]~*~*~*~[#8]', 0) | OAAAO | |
| 90 | ('[$([!#6;!#1;!H0]~*~*~[CH2]~*), $([!#6;!#1;!H0;R]1@[R]@[R]@[CH2;R]1), $([!#6;!#1;!H0]~[R]1@[R]@[CH2;R]1)]',0） |
QHAACH2A | |
| 91 | ('[$([!#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), $([!#6;!#1;!H0]~*~[R]1@[R]@[CH2;R]1)]',0） |
QHAAACH2A | |
| 92 | ('[#8]~[#6](~[#7])~[#6]', 0) | OC(N)C | |
| 93 | ('[!#6;!#1]~[CH3]', 0) | QCH3 | |
| 94 | ('[!#6;!#1]~[#7]', 0) | QN | |
| 95 | ('[#7]~*~*~[#8]', 0) | NAAO | |
| 96 | ('*1~*~*~*~*~1', 0) | 5 M ring | 5元环任意键任意原子 |
| 97 | ('[#7]~*~*~*~[#8]', 0) | NAAAO | |
| 98 | ('[!#6;!#1]1~*~*~*~*~*~1', 0) | QAAAAA@1 | 5元环接杂基团 |
| 99 | ('[#6]=[#6]', 0) | C=C | |
| 100 | ('*~[CH2]~[#7]', 0) | ACH2N | |
| 101 | ('[$([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), $([R]@1@[R]@[R]@[R]@[R] @[R]@[R]@[R]@[R]@[R]@[R]@[R]@[R]@[R]1)]',0） |
8M Ring or larger. This only handles up to ring sizes of 14 | 8元环或以上，最大14 |
| 102 | ('[!#6;!#1]~[#8]', 0) | QO | |
| 103 | ('Cl', 0) | CL | 氯原子 |
| 104 | ('[!#6;!#1;!H0]~*~[CH2]~*', 0) | QHACH2A | |
| 105 | ('*@*(@*)@*', 0) | A$A($A)$A | |
| 106 | ('[!#6;!#1]~*(~[!#6;!#1])~[!#6;!#1]', 0) | QA(Q)Q | |
| 107 | ('[F,Cl,Br,I]~*(~*)~*', 0) | XA(A)A | |
| 108 | ('[CH3]~*~*~*~[CH2]~*', 0) | CH3AAACH2A | |
| 109 | ('*~[CH2]~[#8]', 0) | ACH2O | |
| 110 | ('[#7]~[#6]~[#8]', 0) | NCO | |
| 111 | ('[#7]~*~[CH2]~*', 0) | NACH2A | |
| 112 | ('*~*(~*)(~*)~*', 0) | AA(A)(A)A | |
| 113 | ('[#8]!:*:*', 0) | Onot%A%A | |
| 114 | ('[CH3]~[CH2]~*', 0) | CH3CH2A | |
| 115 | ('[CH3]~*~[CH2]~*', 0) | CH3ACH2A | |
| 116 | ('[$([CH3]~*~*~[CH2]~*),$([CH3]~*1~*~[CH2]1)]', 0) | CH3AACH2A | |
| 117 | ('[#7]~*~[#8]', 0) | NAO | |
| 118 | ('[$(*~[CH2]~[CH2]~*),$(*1~[CH2]~[CH2]1)]', 1) | ACH2CH2A > 1 | |
| 119 | ('[#7]=*', 0) | N=A | |
| 120 | ('[!#6;R]', 1) | Heterocyclic atom > 1 | 杂环原子大于1 |
| 121 | ('[#7;R]', 0) | N Heterocycle | 氮环 |
| 122 | ('*~[#7](~*)~*', 0) | AN(A)A | |
| 123 | ('[#8]~[#6]~[#8]', 0) | OCO | |
| 124 | ('[!#6;!#1]~[!#6;!#1]', 0) | ||
| 125 | ('?', 0) | Aromatic Ring > 1 | 芳香环大于1 |
| 126 | ('*!@[#8]!@*', 0) | A!O!A | |
| 127 | ('*@*!@[#8]', 1) | A$A!O > 1 | |
| 128 | ('[$(*~[CH2]~*~*~*~[CH2]~*), $([R]1@[CH2;R]@[R]@[R]@[R]@[CH2;R]1), $(*~[CH2]~[R]1@[R]@[R]@[CH2;R]1), $(*~[CH2]~*~[R]1@[R]@[CH2;R]1)]',0） |
ACH2AAACH2A | |
| 129 | ('[$(*~[CH2]~*~*~[CH2]~*), $([R]1@[CH2]@[R]@[R]@[CH2;R]1), $(*~[CH2]~[R]1@[R]@[CH2;R]1)]',0） |
ACH2AACH2A | |
| 130 | ('[!#6;!#1]~[!#6;!#1]', 1) | QQ > 1 | |
| 131 | ('[!#6;!#1;!H0]', 1) | QH > 1 | |
| 132 | ('[#8]~*~[CH2]~*', 0) | OACH2A | |
| 133 | ('*@*!@[#7]', 0) | A$A!N | |
| 134 | ('[F,Cl,Br,I]', 0) | X (HALOGEN) | 卤素 |
| 135 | ('[#7]!:*:*', 0) | Nnot%A%A | |
| 136 | ('[#8]=*', 1) | O=A>1 | |
| 137 | ('[!C;!c;R]', 0) | Heterocycle | 是否有杂环 |
| 138 | ('[!#6;!#1]~[CH2]~*', 1) | QCH2A>1 | |
| 139 | ('[O;!H0]', 0) | OH | 氢氧根 |
| 140 | ('[#8]', 3) | O > 3 | 氧原子大于3个 |
| 141 | ('[CH3]', 2) | CH3 > 2 | 甲基大于两个 |
| 142 | ('[#7]', 1) | N > 1 | 氮原子大于1个 |
| 143 | ('*@*!@[#8]', 0) | A$A!O | |
| 144 | ('*!:*:*!:*', 0) | Anot%A%Anot%A | |
| 145 | ('*1~*~*~*~*~*~1', 1) | 6M ring > 1 | 6元环大于1 |
| 146 | ('[#8]', 2) | O > 2 | 氧原子大于2个 |
| 147 | ('[$(*~[CH2]~[CH2]~*),$([R]1@[CH2;R]@[CH2;R]1)]', 0) | ACH2CH2A | |
| 148 | ('*~[!#6;!#1](~*)~*', 0) | AQ(A)A | |
| 149 | ('[C;H3,H4]', 1) | CH3 > 1 | 甲基大于1个 |
| 150 | ('*!@*@*!@*', 0) | A!A$A!A | |
| 151 | ('[#7;!H0]', 0) | NH | 亚氨基 |
| 152 | ('[#8]~[#6](~[#6])~[#6]', 0) | OC(C)C | |
| 153 | ('[!#6;!#1]~[CH2]~*', 0) | QCH2A | |
| 154 | ('[#6]=[#8]', 0) | C=O | |
| 155 | ('*!@[CH2]!@*', 0) | A!CH2!A | |
| 156 | ('[#7]~*(~*)~*', 0) | NA(A)A | |
| 157 | ('[#6]-[#8]', 0) | C-O | |
| 158 | ('[#6]-[#7]', 0) | C-N | |
| 159 | ('[#8]', 1) | O>1 | 氧原子大于1个 |
| 160 | ('[C;H3,H4]', 0) | CH3 | 甲基 |
| 161 | ('[#7]', 0) | N | 氮原子 |
| 162 | ('a', 0) | Aromatic | 芳香结构 |
| 163 | ('*1~*~*~*~*~*~1', 0) | 6M Ring | 6元环 |
| 164 | ('[#8]', 0) | O | 氧原子 |
| 165 | ('[R]', 0) | Ring | 有无环 |
| 166 | ('?', 0) | Fragments FIX: this can't be done in SMARTS | SMARTS编码下无意义 |
References：
- Durant JL, Leland BA, Henry DR, Nourse JG: Reoptimization of MDL keys for use in drug discovery. J Chem Inf Comput Sci 2002, 42:1273-1280.
- THE KEYS TO UNDERSTANDING MDL KEYSET TECHNOLOGY. https://www.3dsbiovia.com/products/pdf/keys-to-keyset-technology.pdf. Accessed Oct. 2019.
- RDKit. https://www.rdkit.org/.
- O'Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR: Open Babel: An open chemical toolbox. J Cheminformatics 2011, 3:33.
- The Open Babel Package. https://openbabel.org.
- Chemistry Development Kit (CDK). Chemistry Development Kit.
- Willighagen EL, Mayfield JW, Alvarsson J, Berg A, Carlsson L, Jeliazkova N, Kuhn S, Pluskal T, Rojas-Cherto M, Spjuth O, Torrance G, Evelo CT, Guha R, Steinbeck C: The Chemistry Development Kit (CDK) v2.0: atom typing, depiction, molecular formulas, and substructure searching. J Cheminformatics 2017, 9:33.