filter

Remove or select molecules with predefined substructures and descriptors

Requirement

• Python 3.6
• RDKit

Usage

Usage: filter.py [OPTIONS] FILENAME

  remove or select molecules by using predefined or custom filters

Options:
  --verbose / --quiet
  -r, --remove TEXT
  -s, --select TEXT
  --identity TEXT      SDF property name for molecule ID
  --check              Check predefined filters
  --cpu INTEGER        Number of CPUs to use
  --help               Show this message and exit.

$ python filter.py --check a

Show all predefined filters and descriptors. Please note that an arbitrary filename "a" is given here.

$ python filter.py test/test.sdf --identity ID --remove lint

Remove compounds that match LINT filters. --identity option is used to find a unique molecular name in case where the first line of SDF file is blank. If --identity option is omitted, it tries to guess a most suitable identity using the properties. Predefined or custom filters can be used after --remove or --select options. A cloest matching and case insensitive fiter names are accepted.

$ python filter.py test/test.sdf -r inphar -s zincfrag

Remove compounds that match Inpharmatica filter and select ZINC fragment definition. --remove (or -r) and --select (or -s) can be used at the same time.

Predefined filters

Name	Description	Reference
PAINS	Pan Assay Interference Compounds (PAINS) (>150 hits)	Baell et al. (2010)
PAINSa	Pan Assay Interference Compounds (PAINS) (>150 hits)	Baell et al. (2010)
PAINSb	Pan Assay Interference Compounds (PAINS) (15-150 hits)	Baell et al. (2010)
PAINSc	Pan Assay Interference Compounds (PAINS) (<15 hits)	Baell et al. (2010)
Dundee	NTD Screening Library	Brenk et al. (2008)
BMS	HTS Deck Filters	Pearce et al. (2006)
Glaxo	Hard Filters	Hann et al. (1999)
LINT	Pfizer LINT Filters	Blake (2005)
MLSMR	NIH Molecular Libraries Small Molecule Repository Excluded Functionality Filters	Dandapani et al. (2012)
Inpharmatica	Unwanted Fragments	ChEMBL
Toxicophore	Toxicophores for Mutagenicity Prediction	Kazius et al. (2005)
ALARM	Abott ALARM NMR Filters for Reactive Compounds	Huth et al. (2005)
SureChEMBL	SureChEMBL filter	ChEMBL
Reactive	reactive functional group
AstexRO3	Astex rule of 3	Astex
Fragment	fragment
AsinexFrag	Asinex's fragment	Asinex
ZincFrag	ZINC's fragment-like	ZINC
Lead-Like	ZINC's lead-like	ZINC
Lipinski	ZINC's drug-like	ZINC
Acid	acid	Hann et al. (1999)
Base	base	Hann et al. (1999)
Nucleophile	nucleophile	Hann et al. (1999)
Electrophile	electrophile	Hann et al. (1999)

Predefined descriptors

All descriptor calculations use RDKit

Name	Description
HAC	Heavyatom (non-hydrogen atom) count
HBA	Number of hydrogen bond acceptor
LipinskiHBA	Number of Lipinski's Hydrogen bond acceptor
HBD	Number of hydrogen bond donor
LipinskiHBD	Number of Lipinski's Hydrogen bond donor
rb	Number of rotatable bond
ring	Number of rings
stereo	Number of atom stereo centers
MolWt	Molecular weight
TPSA	Topological polar surface area
logP	log(partition coefficient between octanol and water)
FCsp3	Fraction of Sp3 carbons

Examples of filters

All filters are defined in XML format and easy to read, write and modify.

predefined/ChEMBL_Walters/Glaxo.xml

<?xml version="1.0" ?>
<Glaxo>
  <group name="(1) R1 Reactive alkyl halides">
    <SMARTS>[Br,Cl,I][CX4;CH,CH2]</SMARTS>
  </group>
  <group name="(2) R2 Acid halides">
    <SMARTS>[S,C](=[O,S])[F,Br,Cl,I]</SMARTS>
  </group>
  ...
</Glaxo>

predefined/ZINC-Lipinski.xml

<?xml version="1.0" ?>
<ZINC-Lipinski>
  <!--definition from zinc.docking.org -->
  <!--Lipinski, J Pharmacol Toxicol Methods. 2000 Jul-Aug;44(1):235-49.-->
  <descriptor name="MolWt">
    <min>150</min>
    <max>500</max>
  </descriptor>
  <descriptor name="logP">
    <max>5.0</max>
  </descriptor>
 ...
</ZINC-Lipinski>

References

1. alert_collection.csv is copied from Patrick Walters' blog and github:
   • http://practicalcheminformatics.blogspot.com/2018/08/filtering-chemical-libraries.html
   • https://github.com/PatWalters/rd_filters
2. Huth JR, Mendoza R, Olejniczak ET, Johnson RW, Cothron DA, Liu Y, Lerner CG, Chen J, Hajduk PJ. ALARM NMR: a rapid and robust experimental method to detect reactive false positives in biochemical screens. J Am Chem Soc. 2005, 127, 217-24.
3. Jeroen Kazius, Ross McGuire, and Roberta Bursi. Derivation and Validation of Toxicophores for Mutagenicity Prediction. J. Med. Chem. 2005, 48, 312-320.
4. J. F. Blake. Identification and Evaluation of Molecular Properties Related to Preclinical Optimization and Clinical Fate. Med Chem. 2005, 1, 649-55.
5. Mike Hann, Brian Hudson, Xiao Lewell, Rob Lifely, Luke Miller, and Nigel Ramsden. Strategic Pooling of Compounds for High-Throughput Screening. J. Chem. Inf. Comput. Sci. 1999, 39, 897-902.
6. Jonathan B. Baell and Georgina A. Holloway. New Substructure Filters for Removal of Pan Assay Interference Compounds (PAINS) from Screening Libraries and for Their Exclusion in Bioassays. J. Med. Chem. 2010, 53, 2719-2740.
7. Bradley C. Pearce, Michael J. Sofia, Andrew C. Good, Dieter M. Drexler, and David A. Stock. An Empirical Process for the Design of High-Throughput Screening Deck Filters. J. Chem. Inf. Model. 2006, 46, 1060-1068.
8. Ruth Brenk, Alessandro Schipani, Daniel James, Agata Krasowski, Ian Hugh Gilbert, Julie Frearson aand Paul Graham Wyatt. Lessons learnt from assembling screening libraries for drug discovery for neglected diseases. ChemMedChem. 2008, 3, 435-44.
9. Sivaraman Dandapani, Gerard Rosse, Noel Southall, Joseph M. Salvino, Craig J. Thomas. Selecting, Acquiring, and Using Small Molecule Libraries for High‐Throughput Screening. Curr Protoc Chem Biol. 2012, 4, 177–191.