The Bemis-Murcko scaffold1 provided by DataWarrior2 retains information about bond order and chirality. Sometimes, however, it suffices to retain only atom connectivity, like an assumption «there are only single bonds». Note, DataWarrior equally offers the export of Bemis-Murcko skeleton, however this simplifies e.g. the scaffold about an imidazole into one of cyclopentane.
Running from the command line, the script processes one, or multiple
SMILES strings listed in an input file (symbolized by text below) to
report the processed SMILES strings back to the command line:
python saturate_murcko_scaffolds.py [-h] [-o] textInstead of an input file, individual SMILES strings equally may be
processed; to prevent their misinterpretation by the shell, enclose them
by either single, or double quotes. Either approach elected, the result
may be redirected into a permanent record with a user defined file name
(flag --outfile, or shorter -o). Only modules the standard library
of Python 3 provides (e.g., version 3.11.2) are used.
For a collection of organic materials, the Bemis-Murcko scaffolds were
extracted with DataWarrior (then release 5.0.0 for Linux, January 2019)
as listing test_input.smi including higher bond orders (see folder
test_data). The effect of the «artificial saturation» is easy to
recognize while comparing the scaffold lists
(fig. file_diff)
in a difference view of the two .smi files.
#, not shown); or about
implicit aromatization (lower case to upper case) for atoms of carbon,
nitrogen, oxygen (depicted); or phosphorus, sulfur (not depicted).
Stereochemical indicators about double bonds will be removed (e.g.,
slashes in lines #18 and #19). Descriptors of stereogenic centers
(@-signs, e.g., line #25) and charges (not shown) are
copied verbatim.
The work can be illustrated by OpenBabel3 with instructions to the command line in the pattern of
obabel -ismi test_input.smi -O test_input_color.svg -xc10 -xr12 -xl --addinindexto generate a .svg file (vector representation), or
obabel -ismi test_input_sat.smi -O test_input_sat_color.png -xc10 -xr12 -xl --addinindex -xp 3000to generate a bitmap .png with structure formulae depicted in a grid
of 10 columns by 12 rows.
It is remarkable how well OpenBabel's displays the molecular structures
with advanced motifs. In addition to those shown in the first
illustration of this guide, see sub-folder test_data for a more
extensive survey (e.g., the scaffold of cyclophane [entry #33],
sparteine [#38], or adamantane [#50]).
The script provides «saturation» by dropping explicit information
related to double and triple bonds which SMILES encode (=, #
regarding bond order; / (forward slash), \ (backward slash)
regarding (cis)-(trans) relationship around double bonds). While
processing double bonds of e.g., ketones to yield secondary alcohols,
the script refrains from the assignment of new CIP priorities and a
corresponding label. It then depends on the program used for a
visualization, if an explicit wedge is used (e.g., OpenBabel), or the
absence of information is highlighted (e.g., as question mark in
DataWarrior, or the project of CDK depict4) as ambiguous. Absolute
configuration of stereogenic centers (indicated in SMILES with the @
sign) already assigned in the input however is retained.
For a selection of elements (C, N, O, P, S), the implicit description of
aromatic systems (e.g., as c1ccncc1 in pyridine, c1c[nH]cc1 in
pyrrol) is recognized. To offer a «saturation», these characters
returned as upper case characters to yield e.g., piperidine (C1CCNCC1)
and pyrrolidine (C1C[NH]CC1).
The script equally preserves up to one single negative, or single
positive charge of these five elements (e.g., [O-]c1ccccc1 about the
phenolate anion, and C[N+](c1ccccc1)(C)C about
N,N,N-trimethylbenzenaminium cation). Here, it can be sensible to
«sanitize» the results this script provides by other libraries as e.g.
RDKit.5
The capitalization of the five characters is constrained to prevent non
sensible transformations of e.g., an (implicitly) aromatic atom of tin
[sn] into the invalid form [SN]. Though the script is going to write
tin as [Sn], an adjustment of valence for elements written with two
characters is beyond the current scope of the script.
A SMILES string may describe more than one molecule. Thus, the
concatenation with "." (period character) as seen for example in
descriptions of co-crystals like about 1,4-benzoquinone and
hydroquinone, C1=CC(=O)C=CC1=O.c1cc(ccc1O)O, is retained. The example
is resolved as C1CC(O)CCC1O.C1CC(CCC1O)O.
Norwid Behrnd, 2019–23, GPLv3.
Footnotes
-
Bemis, G. W.; Murcko, M. A. The Properties of Known Drugs. 1. Molecular Frameworks. J. Med. Chem. 1996, 39, 2887–2893 (https://doi.org/10.1021/jm9602928). ↩
-
Sander, T.; Freyss, J.; Von Korff, M.; Rufener, 1. DataWarrior: An Open-Source Program For Chemistry Aware Data Visualization And Analysis. J. Chem. Inf. Model. 2015, 55, 460–473 (https://doi.org/10.1021/ci500588j). The program, (c) 2002–2023 by Idorsia Pharmaceuticals Ltd., is freely available under http://www.openmolecules.org. For the source code (GPLv3), see https://github.com/thsa/datawarrior. ↩
-
www.openbabel.org For the most recent documentation, see https://open-babel.readthedocs.io/en/latest/ReleaseNotes/ob310.html ↩
-
https://www.simolecule.com/cdkdepict/depict.html For the mentioned annotation of CIP labels, change
No Annotation(second pull down menu from the left) toCIP Stereo Label. ↩ -
For an overview about the freely available RDKit library, see www.rdkit.org. An introduction into the topic of «molecular sanitization» is provided in the section of this very title in the on-line RDKit Book. ↩