Overview

High-throughput screening (HTS) and virtual screening (VS) are widely applied in compounds screening and lead discovery. However, the frequent appearances of “noisy compounds” in the screening database, such as compounds with poor drug-likeness, compounds with poor selectivity or compounds with potential toxicity, have greatly weakened the efficiency of HTS and VS campaigns. The success of screening results critically depends on the quality of the available screening libraries. To construct a high-quality database, we developed Scopy (Screnning COmpounds in PYthon), an integrated negative design python library designed for screening out undesiable compounds in the early drug discovery. Scopy includes six modules, covering data preparation, screening filters, the calculation of scaffolds and descriptors, and the visualization analysis.

The Python package Scopy is designed by CBDD Group (Computational Biology & Drug Design Group), Xiangya School of Pharmaceutical Sciences, Central South University.

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Who uses Scopy?

Scopy is a comprehensive and uniform Python package which aims at providing an integrated pipeline for molecule analysis, molecule screening, molecule optimization and model building. Researchers who want to build a desirable screening database, evaluate initial hits quality, or need pertinent suggestions in molecular optimization, can use Scopy as a credible and efficient tool. We believe that, by the rational application of Scopy, users can draw useful knowledge and experience across many disciplines, thus decreasing the time and cost for drug research.

Motivation

Scopy is intended to provide

  • Tools for pretreating molecules

  • Calculation of molecular physicochemical (PC) properties and screening drug-likeness filters

  • Detection of potential toxicophores

  • Detection of function groups related with frequent hitters

  • Calculation of substructure descriptors, fingerprints and scaffold

  • Visualization of molecular features and screening results

Feature overview

Scopy contains six individual modules: (1) molecular preparation; (2) physicochemical properties and drug-likeness rules; (3) Molecular representations from substructure descriptors, fingerprints and molecular scaffolds; (4) FH substructure filters; (5) toxicophore filters and (6) the visualization analysis.

Type

Detail

Description

Drug-likeness Filter

Basic PC Properties
  • Molecular Weight >>> MW

  • Molecular Volume >>> Vol

  • Molecular Density >>> Dense

  • Formal Charge >>> fChar

  • Number of bonds >>> nBond

  • Number of atoms >>> nAtom

  • Number of heteroatoms >>> nHet

  • Number of heavy atom >>> nHev

  • Number of rotatable bonds >>> nRot

  • Number of rigid bonds >>> nRig

  • Molecular Flexibility >>> Flex

  • Number of SSSR >>> nRing

  • logP >>> logP

  • logD >>> logD

  • logSw >>> logSw

  • Acid or Base >>> ab

  • pKa >>> pKa

  • Molecular refraction >>>MR

  • Number of hydrogen bond donors >>> nHD

  • Number of hydrogen bond acceptors >>> nHA

  • Number of hydrogen bond donors& acceptors >>> nHB

  • Aromatic proportion >>> AP

  • Sp3 hybridized carbons/total carbon count >>> Fsp3

  • TPSA >>> TPSA

  • Size of biggest system ring >>> MaxRing

  • Number of stereo-centers >>> nStereo

  • HetCarbonRatio >>> HetRatio

  • Number of single bonds >>> nSingle

  • Number of double bonds >>> nDouble

  • Number of triple bonds >>> nTriple

  • Number of Carbon atoms >>> nC

  • Number of Boron atoms >>> nB

  • Number of Chlorine atoms >>> nCl

  • Number of Bromine atoms >>> nBr

  • Number of Iodine atoms >>> nI

  • Number of Phosphor atoms >>> P

  • Number of Sulfur atoms >>> nS

  • Number of Oxygen atoms >>> nO

  • Number of Nitrogen atoms >>> nN

Specific PC Properties
  • QED with average descriptor weights >>> QEDmean

  • QED with maximal descriptor weights >>> QEDmax

  • QED with using unit weights >>> QEDnone

  • synthetic accessibility score >>> SAscore

  • Natural product- likeness score >>> NPscore

ScoDruglikeness

Drug-likeness Rules (Small Molecule)
  • Egan Rule

  • Veber Rule

  • LipinskiRule

  • Pfizer Rule

  • GSK Rule

  • Oprea Rule

  • Ghose Rule

  • Xu Rule

  • Ro4 Rule

  • REOS Rule

  • GoldenTriangle

Drug-likeness Rules (Macro Molecule)
  • BeyondRo5

  • OralMacrocycles

Drug-likeness Rules (Building Block)
  • Ro3 Rule

  • Ro2 Rule

Frequent Hitters Filter

Assay interference
  • AlphaScreen_FHs(6)

  • Luciferase_Inhibitory(3)

  • Chelating(55)

  • Alarm_NMR(75)

Promiscuous compounds
  • AlphaScreen_GST_FHs(34)

  • AlphaScreen_HIS_FHs(19)

  • PAINS(480)

  • BMS(176)

ScoFH

Toxicity Filter

Human Toxicity
  • Potential_Electrophilic(119) #i.e.Broad Toxicity Rule

  • LD50_oral(20) #i.e.Acute Toxicity Rule

  • Genotoxic_Carcinogenicity_Mutagenicity(117)

  • NonGenotoxic_Carcinogenicity(23)

  • Skin_Sensitization(155)

Comprehensive Toxicity
  • NTD(105)

  • SureChEMBL(165)

  • Toxicophores(154)

Envrionment Toxicity
  • Acute_Aquatic_Toxicity(99)

  • Biodegradable(9)

  • NonBiodegradable(19)

ScoTox

Chemical Space Exploer

Substurecture Descriptor
  • MACCS(167 bits)

  • EFG(583 bits)

  • PubChem(881 bits)

  • EState(79 bits)

  • GhoseCrippen(110 bits)

  • IFG

Fingerprint
  • Morgan(1024 default)

  • Daylight(2048 default)

Framework
  • Murcko Framework

  • Carbon Scaffold

ScoRepresent

The Python programming language

Python is a powerful programming language that allows simple and flexible representations of biochemical molecules, and clear and concise expressions of bioinformatics algorithms. Python has a vibrant and growing ecosystem of packages that Scopy uses to provide more features such as RDkit. In addition, Python is also an excellent “glue” language for putting together pieces of software from other languages which allows reuse of legacy code and engineering of high-performance algorithms. Equally important, Python is free, well-supported, and a joy to use. In order to make full use of Scopy, you will want to know how to write basic programs in Python. Among the many guides to Python, we recommend the documentation at https://www.python.org/