MNA

The Multilevel Neighbourhoods of Atoms (MNA) de= scriptors represent a molecule as a set of character strings. An example of MNA descriptors is given below for Paracetamol:

CHHHC

CHCC

CCCN

CCCO

CCNO

NHCC

OHC

C(C(CC-= H)C(CC-H)-N(C-H-C))

C(C(CC-H)C(CC-H)-O(C-H))

C(C(CC-H)C(CC-N)-H= (C))

C(C(CC-H)C(CC-O)-H(C))

-H(C(CC-H))

-H(-C(-H-H-H-C))<= /p>

-H(-N(C-H-C))

-H(-O(C-H))

-C(-H(-C)-H(-C)-H(-C)-C(-C-N-O)= )

-C(-C(-H-H-H-C)-N(C-H-C)-O(-C))

-N(C(CC-N)-H(-N)-C(-C-N-O))

-O(C(CC-O)-H(-O))

-O(-C(-C-N-O))

An important feature of the MNA descriptors is that they are constructed= directly using the structural formula rather than a prescribed list of str= uctural fragments. Yet another feature of these descriptors consists in tha= t they retain the integrity of structural fragments in the sense that for e= ach MNA descriptor the researcher can draw the corresponding structural fra= gment provided some skill.

The 2D structural formulae of compounds were chosen as the basis for description of chemical structure because this is the only informatio= n available in the early stage of research. The MNA descriptors are based o= n the molecular structure representation, which includes the hydrogens acco= rding to the valences and partial charges of other atoms and does not speci= fy the types of bonds.

The MNA descriptors are generated as recursively defined sequence:

zero-level MNA descriptor for each atom is the mark A<= /strong> of the atom itself;

any next-level MNA descriptor for the atom is the sub-structure notatio= n A(D₁D₂= =E2=80=A6D_i=E2=80=A6),

where D_i is the previous-level MNA = descriptor for =E2=80=93th immediate neighbour=E2=80=99s of the atom A.

The mark of atom may include not only the atomic type but also any addit= ional information about the atom. In particular, if the atom is not include= d into the ring, it is marked by =E2=80=9C-=E2=80= =9D. The neighbour descriptors D₁D₂= =E2=80=A6D_i=E2=80=A6 are arranged in unique ma= nner, e.g., in lexicographic order. Iterative process of MNA descriptors ge= neration can be continued covering first, second, etc. neighbourhoods of ea= ch atom.

The molecular structure is represented by the set of unique MNA descript= ors of the 1^st and 2^nd levels. Since MNA descriptors = do not represent the stereochemical peculiarities of a molecule, the substa= nces whose structures differ only stereochemically, are formally considered= as equivalent.

The MNA descriptors (for prediction of activity spectra or for adding su= bstances to SAR Base) are generated only if structure corresponds to t= he following criteria:

each of the atoms in a molecule must be presented by atom symbol from t= he periodic table. Symbols of unspecified atom A, Q, *, or R group labels a= re not allowed;
each of the bonds in a molecule must be covalent bond presented by sing= le, double or triple bond types only;
structure must include three or more carbon atoms;
structure must include only one component. Single atom parts like HCl, = Cl^-, OH^-, Na⁺, etc., (hydrogen atoms do no= t take into account) are excluded from MNA descriptors generation;
structure (main part, see the previous sentence) must be uncharged;
the absolute molecular weight of a substance must be less than 1250.

REFERENCES

V. V. Poroikov, D. A. Filimonov, T. A. Gloriozova, A. A. Lagunin, D. S.= Druzhilovskiy, A. V. Rudik, L. A. Stolbov, A. V. Dmitriev, O. A. Tarasova,= S. M. Ivanov, P. V. Pogodin. Computer-aided prediction of biological activ= ity spectra for organic compounds: the possibilities and limitations. R= uss. Chem. Bull., Int. Ed., 2019, 68, 2143=E2=80=9321= 54. https://doi.org/10.1007/s11172-019-2683-0
D. A. Filimonov, A. A. Lagunin, T. A. Gloriozova, = A. V. Rudik, D. S. Druzhilovskii, P. V. Pogodin, V. V. Poroikov. Prediction= of the Biological Activity Spectra of Organic Compounds Using the Pass Onl= ine Web Resource. Chemistry of Heterocyclic Compounds, 2014, 50, 444-457. https://doi.org/10.1007/s10593= -014-1496-1
Filimonov D.A., Poroikov V.V. Probabilistic approach in activity predic= tion. In: Chemoinformatics Approaches to Virtual Screening. Eds. A= lexandre Varnek and Alexander Tropsha. Cambridge (UK): RSC Publishing, 2008, 182-216.

Lagunin A., Stepanchikova A., Filimonov D., Poroikov V. PASS: predictio= n of activity spectra for biologically active substances. Bioinformatic= s, 2000, 16, 747-748. https= ://doi.org/10.1093/bioinformatics/16.8.747

Poroikov V. V., Filimonov D. A., Borodina Yu. V., Lagunin A. A., Kos A.= Robustness of Biological Activity Spectra Predicting by Computer Program P= ASS for Noncongeneric Sets of Chemical Compounds. J. Chem. Inf. Comput.= Sci., 2000, 40, 1349-1355. https://doi.o= rg/10.1021/ci000383k

Filimonov D., Poroikov V., Borodina Yu., Gloriozova T. Chemical Similar= ity Assessment through Multilevel Neighborhoods of Atoms: Definition and Co= mparison with the Other Descriptors. J. Chem. Inf. Comput. Sci., 1= 999, 39, 666-670. https://doi.org/10.1021/ci98= 0335o

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