Review of bioinformatic tools used in Computer Aided Drug Design (CADD)

Namitha K N * and V Velmurugan

Department of Pharmaceutical Chemistry, SRM College of Pharmacy SRMIST, Chennai, Tamil Nādu, India.

World Journal of Advanced Research and Reviews, 2022, 14(02), 453–465

Publication history: Received on 29 March 2022; revised on 04 May 2022; accepted on 06 May 2022

Article DOI: https://doi.org/10.30574/wjarr.2022.14.2.0394

Abstract
Drug discovery is а time consuming рrосess of finding out a new drug molecule. The process takes many years to
complete and needs human resource. These is difficulties have been overcome by introducing computer programmes
in drug discovery (CADD) which includes target identification, hit identification, and molecular modification of а lead
compound to optimize desired effects and minimize side effects, based on the knowledge of their biological targets.
Molecular modelling is the process of designing a molecule with a computer-based collection of programmes (in-silico
design) for deriving, representing, and manipulating the structures and reactions of molecules. Numerous Software
tools, online data bases and computer programmes are used in the field of CADD in which some relevant, user friendly
and precise ones are reviewed in this article. Software is available for personal use and for commercial purposes. All
these tools are highly useful in the field of drug design and discovery. The article will be helpful for selecting a tool for
computer aided drug design.

Keywords: CADD; Drug Discovery; Software; Autodock

1. Introduction
Drug discovery is а lengthy рrосess of finding out a new drug molecule by complex synthetic and analytical procedures.
The process takes many years to complete and is difficult if we follow the conventional methods. These difficulties have
been overcome by introducing computer programmes in drug discovery. The main advantage of Computer-Aided Drug
Design (CADD) is the reduction of the time and human resources needed for the рrосess of drug discovery. CADD helps
us design а molecule by modifying а pre-existing drug molecule or by newly inventing а molecule to predict its possible
biological activities. It includes target identification, hit identification, and molecular modification of а lead compound
to optimize desired effects and minimize side effects, based on the knowledge of their biological targets.

CADD can increase the hit rate of novel drug compounds in the drug design as it uses а more targeted search than
traditional High Throughput Screening (HTS) and combinatorial chemistry. It aims to explain a drug’s molecular basis
and therapeutic activity and to predict possible derivatives that would improve the biological activity by minimizing the
undesired effects. A lead compound is a molecule having a particular biological activity obtained either from a natural
or synthetic source [1].

Structure-based computer-aided drug design relies upon the ability to determine and analyze three dimensional (3D)
structures of biological target molecules. The core hypothesis of this approach is that a molecule’s ability to interact
with a specific target protein and exert a desired biological effect depends on its ability to favorably interact with a
particular binding site on that target. Molecules that share those favorable interactions will also exert similar biologic
effects [25].


Corresponding author: Namitha KN
Department of Pharmaceutical Chemistry, SRM College of Pharmacy SRMIST, Chennai, Tamil Nādu, India..
Copyright © 2022 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0.
 World Journal of Advanced Research and Reviews, 2022, 14(02), 453–465

Ligand-based drug design trusts the awareness of new ligand molecules that bind with the target protein molecule.
These differently designed molecules are used to develop a new strategy that explains each element responsible for the
interaction between ligand and target molecule. Ligand-based drug design depends on small molecules that bind to the
active binding site of the biological target with their interest [2]. These molecules are used to extract a suitable model
that provides the important structural properties of a lead molecule, which helps in the binding process with the target
molecule. It is otherwise called indirect drug design.

Molecular modelling is the process of designing a molecule with a computer-based collection of programmes (in-silico
design) for deriving, representing, and manipulating the structures and reactions of molecules. The properties of these
molecules are dependent on their three-dimensional structures. Several computer-based programmes suitable for in-
silico drug design have been developed during these years in which the most reliable ones have been reviewed here in
this article [13].

Ideally the computational method should be able to predict affinity before a compound is synthesized and hence in
theory only one compound needs to be synthesized. The reality however is that present computational methods are
imperfect and provide at best only qualitatively accurate estimates of affinity. Therefore, in practice, it still takes several
iterations of design, synthesis, and testing before an optimal molecule is discovered. On the other hand, computational
methods have accelerated discovery by reducing the number of iterations required and in addition have often provided
more novel small molecule structures [3,8].

1.1. Docking
Docking means a computational simulation of a candidate ligand binding to a receptor. In molecular modelling, docking
is used to predict how a target protein will interact with a small molecule. The flexibility of molecules plays a crucial
role in docking analysis.

1.2. Rigid Docking and Flexible Docking

Rigid docking means there is no modification in the bond angles, bond lengths and torsion angles of the components at
any stage of complex generation, whereas in flexible docking, we can modify all these, which permits conformational
change and results in the best-docked pose.[12].

2. Material and methods

2.1. Molecular Editors and Visualization Tооls

Molecular editors are the commonly used tools to draw and manipulate chemical structures. These tools also provide
several facilities such as geometry optimisation, structure visualisation, energy minimisation and three-dimensional
image creations.

Many tools are used in computer-aided drug design for different purposes like creating 3D structures of chemical
entities, creating SMILES notations, 3D molecular visualisation tools, prediction of pharmacological activities, toxicity
predictions, and docking studies. These tools help design a new chemical entity to produce a desired pharmacological
effect [4,19]. Here we discuss some newly introduced software that can be used as the best tools for in-silico drug design
studies.

2.2. Graphical User Interface

Several computer programmes can be utilised as drug design and development tools, providing all the basic
functionalities related to the drug design. Some important ones are reviewed below.

2.3. Molecular viewers and Editors

Molecular viewers and editors are used to view the 3-dimensiоnаl structure of both small molecules and biological
macromolecules such as proteins.

2.3.1. Molecular Operating Environment (MОE)

MOE is one of the computer-based software tools designed to support Cheminformatics and drug design. MOE is good
with its wide-ranging, flexible, and high-quality modelling tools ranging from protein modelling applications to
cheminformatics and statistical data analysis tools. It provides a wide variety of operations such as three-dimensional

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molecular visualisation, structure-based drug design, molecular simulations, peptide modelling, QSAR, structural
bioinformatics, Structure-Activity Relationship (SAR) Explorer, Ligand Based Drug design, Protein, DNA/RNA
modelling, Virtual screening, and antibody design [17,29].

2.3.2. SYBYL-X
It is a comprehensive molecular modelling and simulation suite developed to accelerate the process of drug design and
other molecular discovery projects, from high throughput screening to late lead optimisation. Its latest version, SYBYL-
X 2.1, features a new Job Control System which provides a consistent interface across the entire tool suite. This feature
enables users to submit their jobs remotely from Windows, Linux, or Mac to any Linux system where SYBYL-X is
installed. It also provides improved multi-processor support for key applications such as Surflex-Sim, Surflex-Dock,
Topomer Search, and UNITY. A Python toolkit for 3D-QSAR makes QSAR functionality accessible outside of SYBYL-X as
standalone Python scripts have also been incorporated [5,6].

2.3.3. Accelrys Discovery Studio

Accelrys Discovery Studio is a software suite from Biovia for simulating small molecule and macromolecule systems,
including silico techniques such as molecular mechanics, free energy calculations, and biotherapeutics developments.
It is an apt tool to explore biological and physicochemical processes down to the atomic level [16,19]. A researcher must
optimise both biochemical potency and, at the same time, optimise other characteristics such as ADME and toxicity. It
is an advanced tool for protein chemistry and discovering small and large molecule therapeutics from target
identification to lead optimisation [32,43]. It is a key aspect of the analysis and designing of a molecule. It also includes
a graphical visualisation tool for viewing, sharing, and analysing protein and modelling data.

2.3.4. IСM Pro

ICM-Pro helps a biologist or chemist by providing a high-quality protein structure analysis, modelling, and docking
desktop software environment. There will be direct access to sequence and structural databases, which allows for all
the jobs related to drug design and development. Its key features include Protein Structure Analysis, Pocket Finder, 3D
Interactive Editor, Small Molecule Docking, Protein-Protein Docking, Protein Structure Prediction, Predict Effect of
Mutation, Bioinformatics Tools, Electrostatics, and molecular graphical tools [5,6 27].

2.3.5. PyMOL
PyMOL is a molecular visualisation system on an open-source foundation, maintained and distributed by Schrodinger.
It supports all the operating systems like Windows, iOS, and Linux. PyMOL 2.5 is the latest version for this.

2.3.6. Сhem3D
Chem 3D is a tool to produce colourful three-dimensional chemical structures useful in presentations, posters, and drug
designing. It can be used to convert a two-dimensional structure to a three-dimensional structure. It can convert an
image in CIF format to a PDB file. It is also useful to visualise, manipulate, calculate bond lengths and angles, perform
molecular modelling calculations, and perform molecular dynamics calculations [22,91].

2.3.7. Chimera
UCSF ChimeraX (or simply ChimeraX) is the next-generation molecular visualisation program from the Resource for
Biocomputing, Visualization, and Informatics (RBVI), following UCSF Chimera. UCSF Chimera is a program for the
interactive visualisation and analysis of molecular structures and related data, including density maps, trajectories, and
sequence alignments. It is available in both free (non-commercial) and commercial forms [7,9].

2.3.8. Jmol
It is a free and open-source three-dimensional chemical structure writing tool used in drug design. It is cross-platform,
running on Windows, iOS, and Linux/Unix systems. The Jmol Viewer is a development tool kit that can be integrated
into other Java applications. It supports all major web browsers: Firefox, Safari, Chrome, Opera, and Edge. High-
performance 3D rendering with no hardware requirements is the advantage [10,18].

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2.4. Chemical drawing and visualization software

2.4.1. PubChem sketcher

It is a network-based tool for molecular sketching which is incorporated with PubChem. It is a web-based information
pool for chemical and bioactivity. It is a Web-bas0ed drawing tool for interactive sketching of chemical structures. It is
a complete platform for independent and verified work on all major Web browsers, including older ones without
support for Web2.0 JavaScript objects [11,15].

2.4.2. ChemSketch
ChemSketch is a drawing package that allows drawing chemical structures, including organics, organometallics,
polymers, and Markush structures. It also includes calculation of molecular properties like molecular weight, density,
molar refractivity, 2D and 3D structure cleaning and viewing, functionality for naming structures (fewer than fifty atoms
and three rings), and prediction of logP. The freeware version of ChemSketch does not include all of the functionality of
the commercial version. Visit ACD/ChemSketch to learn more about the commercial version [14,28].

2.4.3. Сhemdrаw
KingDraw is a free chemical drawing editor that allows users to sketch molecules, reactions, and organic chemistry
objects and pathways. Users can also use it to analyse compound property, convert chemical structures to IUPAC names
and view 3D models. KingDraw will provide strong software support for chemical research, including more chemical-
related functions and new structure drawing modes to connect Android & iOS devices and PC, realising rapid
transforming from KingDraw to Office, ChemDraw and picture. It has many powerful functions, like AI image
identification, intelligent gesture drawing, clean up structure, get 3D model, conversion between name and structure,
structural formula searching, chemical property analysis, built-in group and free sharing [16,20,].

2.4.4. Сhemdооdle
XDrawChem is a two-dimensional molecule drawing program for Unix operating systems. It is similar to other molecule
drawing programs such as ChemDraw (TM, CambridgeSoft). It can read and write MDL Molfiles and read ChemDraw
text and binary files to allow sharing between XDrawChem and other chemistry applications, and it can create images
in popular formats like PNG and EPS. XDrawChem has been tested on Linux, SGI IRIX 6.5, Sun Solaris, Mac OS X, and
Windows [21,23].

2.4.5. Mаrvin Suite

Marvin suite is a chemically intelligent desktop toolkit that helps draw, edit, publish, render, import and export chemical
structures and allows conversion between various chemical and graphical file formats. It is free for individual, academic
and non-commercial use. MarvinSketch features extensive functionalities to enable the fast and accurate drawing of
chemical compounds, reactions, Markush structures, and query molecules. MarvinView is an advanced chemical viewer
for single and multiple 2D/3D chemical structures, queries, reactions, and associated data. It also supports the widest
selection of industrially acknowledged standard chemical file formats [24,26].

2.4.6. BKСhem
It is a free chemical drawing program. It was conceived and written by Beda Kosata and is currently maintained by
Reinis Danne. BKChem is written in Python, an interpreted and excellent programming language, implying some of the
program features:

• Platform independence – It runs on any platform that Python does.

• Performance - as Python is interpreted language, one should not expect the performance of a native code
compiled application (in present days, a cheap trade-off for platform independence). It is developed on
GNU/Linux. It was, however, successfully used under Windows XP and MacOS X.

2.4.7. MedСhem Designer

It is a tool that combines innovative molecule drawing features with fast and accurate ADMET property predictions
from our top ranked ADMET Predictor. Chemists who design new compounds for pharmaceutical, cosmetic, industrial
chemical, herbicide, pesticide, and food applications will enjoy the highly intuitive interface with several convenience
features and capabilities not available in other molecule drawing software [27].

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2.4.8. Activity Miner

The Activity Miner component of Flare™ enables rapid navigation of complex SAR while highlighting key activity
changes. Dedicated interfaces enable detailed investigation of activity cliffs and near neighbours to enhance
understanding. It can compare selected molecules for changes in electrostatics, shape, protein interactions or clusters
using 3D or 2D relationships. Activity Miner explains the reasons behind an activity change. It offers multiple data views
to help find key molecule pairs in SAR. For each pair, Activity Miner shows how the electrostatic and shape properties
differ, building an understanding of designing better compounds with better properties. The different views enable the
user to focus on various aspects of SAR [32,39].

2.4.9. Flare
Flare Viewer is a free version of Flare ligand-based and structure-based drug design solution enabling research chemists
to discover novel small molecules more efficiently and effectively in a single platform. It is used for the design and
Optimisations of ligand binding [44,64].

2.4.10. Ligаnd Sсоut

Ligand Scout is software used for creating three-dimensional (3D) pharmacophore models from structural data of
macromolecule–ligand complexes. It incorporates the 3D chemical features such as hydrogen bond donors, acceptors,
lipophilic areas, positively and negatively ionisable chemical groups that describe the interaction of a bound small
organic molecule (ligand) and the surrounding binding site of the macromolecule. These pharmacophores can be
overlaid and superimposed using a pattern-matching based alignment algorithm based solely on pharmacophoric
feature points instead of chemical structure. The software has successfully predicted new lead structures in drug design
[40,87].

2.4.11. СhemBiоDrаw
ChemDraw, available from CambridgeSoft, has long been the preferred package for drawing chemical structures for
publication-quality graphics. It also has been used as the drawing package for database queries and electronic
notebooks. The package has developed enhancements such as NMR spectra prediction, TLC plate tools, molecular and
physicochemical property calculations, and structure naming. With the latest version (Version 11), perhaps the first
surprise is the name change to reflect the increased emphasis on the biological drawing features of BioDraw [30,31].

2.4.12. СhemАxоn
It provides several desktop tools such as the drawing tool Marvin and plugins to calculate various physicochemical
properties. A tool to calculate pKa and the resulting LogD, the essential physicochemical property in medicinal
chemistry. There are command-line versions of these calculations that are invaluable for dealing with huge datasets,
and these were used in a script to analyse fragment collections [81,83].

2.4.13. FоrgeV10
ForgeV10 allows the scientist to use Cresset’s proprietary electrostatic and physicochemical fields to align, score and
compare diverse molecules. It allows the user to build field-based pharmacophores to understand structure-activity
and then use the template to undertake a virtual screen to identify novel scaffolds [57,34].

2.4.14. Vortex
Vortex is a chemically aware data analysis and spreadsheet tool from Dotmatics. It can import files from a SQL database
and do substructure or structural similarity searches. Calculate many physicochemical properties and perform data
analysis and display. It is an interactive data visualisation and analysis solution for scientific decision support. Building
on and extending the spreadsheet paradigm, it provides the data manipulation, statistical analysis and sophisticated
plotting capabilities required to explore and understand any complexity and size of data. Vortex is also scientifically
aware, providing native cheminformatics and bioinformatics analysis and visualisations [80,93,].

2.4.15. Mоlinsрirаtiоn
Molinspiration offers a broad range of cheminformatics server tools supporting molecule manipulation and processing,
including SMILES and SD file conversion, normalisation of molecules, generation of tautomer’s, molecule fragmentation,
calculation of various molecular properties needed in QSAR, molecular modelling and drug design, high-quality
molecule depiction, molecular database tools supporting substructure and similarity searches. Our products also

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support fragment-based virtual screening, bioactivity prediction and data visualisation. Molinspiration tools are written
in Java and can be used on any computer platform [50,63].

2.4.16. Ассоrd for Excel

Accord for Excel is a valuable tool used by all the synthetic chemists at Biovitrum. We first acquired Accord with the
combinatorial chemistry add-in to provide an easy-to-use method for chemists (both medicinal and combinatorial) to
enumerate libraries and combine structural and analytical data, often exported from instruments in Excel format. It
provides us with a convenient method of moving chemical structures and data between systems and performing simple
calculations on those structures [47,54].

2.4.17. Docking tools

Some docking applications will generate a 3D structure and multiple conformations of the proposed ligand, and many
also include a variety of scoring functions to rank the proposed poses.

2.4.18. SeeSAR
It is a virtual drug design platform. Quick and informative calculations can be used to dock, design, and analyse a new
chemical entity in a flash. It evaluates ligand-target interactions by intuitive colour codes and gorgeous visualisation.
Drag and Drop facilities for both ligands and targets are available. If we choose the structure-based drug design, there
may be facilities to edit the target protein virtually. The most exciting part of the platform is its Inspirator mode which
gives new ideas to discover new scaffolds, explore and grow into free cavities, or link molecules using fragment libraries
for elegant solutions [59,60,82].

2.4.19. AutoDock
Autodock is a suite of automated docking tools. It is designed to predict how small molecules, such as substrates or drug
candidates bind to a known 3D structure receptor. It has been modified and improved to add new functionalities, and
multiple engines have been developed. Now two major generations are there: AutoDock 4 and AutoDock Vina.
AutoDock-GPU is an accelerated version of AutoDock4 that is hundreds of times faster than the original single-CPU
docking code. It can also help to guide organic synthetic chemists to design better binders [68,69].

2.4.20. Autodock Vina

Autodock is one of the docking engines of the AutoDock Suite, an open-source program for molecular docking. It is more
accurate than Autodock. It is more compatible and easier to use.

2.4.21. Swiss dock

It is an online docking web service that provides services to dock and predict molecular interactions between a
biological target molecule and a ligand drug molecule. It consists of a database, namely S3DB, which manually curates
target and ligand structures inspired by the Ligand-Protein Database. It can generate a complex to perform subsequent
calculations. It works on its own server for docking, giving an accurate docked score compared to others. The time taken
for docking may vary. Large molecules cannot be used on this service [70,79].

2.4.22. InfiniSee
InfiniSee is a virtual screening platform. It finds molecules of interest in chemical spaces of (almost) infinite size based
on similarity. Given a template or query molecule, infiniSee returns similar molecules from these chemical spaces or
screening libraries [75].

2.4.23. Zdосk
Zdock performs a full rigid-body search of docking orientations between two proteins. The current version, 3.0.2,
includes performance optimisation and a novel pairwise statistical energy potential. M-ZDOCK: A modification of ZDOCK
to predict symmetric assemblies using a subunit structure. ZRANK: A docking refinement program developed to provide
fast and accurate rescoring of models from initial-stage docking (e.g., from ZDOCK), as well as refined docking models
(e.g., from Rosetta Dock). ZDOCK Server: a protein docking server permitting users to run the latest versions of ZDOCK
[73,89].

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2.4.24. GОLD
It is the validated, configurable protein-ligand docking software for expert drug discovery from virtual screening to lead
optimisation. The extensively validated scoring functions in GOLD can be trusted. It has the features of pose prediction,
multiple scoring functions, flexible docking, virtual screening, water handling and covalent docking.

2.4.25. Glide
Glide offers the full range of speed vs accuracy options, from high-throughput virtual screening mode for efficiently
enriching million compound libraries to the standard precision mode for reliably docking tens to hundreds of thousands
of ligands with high accuracy, to the XP (extra precision) mode where further elimination of false positives is
accomplished by more extensive sampling and advanced scoring, resulting in even higher enrichment [86,62].

2.4.26. FlexAID
It is a molecular docking software that can use small molecules and peptides as ligands and proteins and nucleic acids
as docking targets. As the name suggests, FlexAID supports complete ligand flexibility and side-chain flexibility of the
target. It does use a soft scoring function based on the complementarity of the two surfaces [58,76].

2.4.27. GEMDOCK
The generic evolutionary method of docking is named GEMDOCK. It is a program for computing a ligand conformation
and orientation relative to the target protein’s active site. It may run as either a purely flexible or hybrid docking
approach. It automatically generates all docking variables, such as atom formal charge, atom type, and the ligand-
binding site of a protein. It is now accompanied by many add-on programmes, making it truly convenient and less time-
consuming [71,72].

2.4.28. MS-Dосk
MS-DOCK is an efficient multiple conformation rigid-body docking approach based on DOCK. It can be easily used for
the generation of multi-conformer libraries and for shape-based filtering within a multi-step structure-based screening
protocol to shorten computation time [42,53].

2.4.29. Ligand Fit

Ligand Fit is a shape-based method for accurately docking the ligands into a protein’s active binding site. The method
employs a cavity detection algorithm for detecting invaginations in the protein as candidate active site regions.
Candidate poses are minimised in the context of the active site using a grid-based method for evaluating protein-ligand
interaction energies [35,36].

2.4.30. UСSF Dосk

UCSF dock is another docking software in which DOCK6 is the latest version written in C++ and is functionally separated
into independent components allowing a high degree of flexibility. It needs about 100 MB of disk space. The new features
added include additional scoring options for energy minimisation, Delphi electrostatics, ligand conformational entropy
corrections, ligand desolvation, receptor desolvation, receptor flexibility, conjugate grading minimization [55,56].

2.4.31. GalaxyPepDock
GalaxyPepDock is a web server-based protein-protein docking interface. It performs similarity-based docking by finding
templates from the database of experimentally determined structures and building models using energy-based
optimisation that allows for structural flexibility [52, 41].

2.4.32. Stаrdrор
It is one of the best in-silico technological tools used in Cheminformatics, model building and analysis of chemical
entities in drug design and development. It brings about the latest data of drug molecules and targets, which is extremely
helpful in predicting biological activity and molecular modelling. It is the best tool to rely on for decision-making while
researching drug design. Both the free version and commercial versions are available for this [66,49].

2.4.33. rDock
rDock is a fast and versatile open-source program for docking ligands to proteins and nucleic acids, primarily designed
for high-throughput virtual screening and prediction of binding mode [38, 67].

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2.5. Biological Activity Prediction Tools

2.5.1. Wаy2Drug
Way2Drug portal has been developed and supported by the multidisciplinary team of researchers working in
bioinformatics, cheminformatics, and computer-aided drug discovery for about thirty years. It provides a local
correspondence concept, according to which biological activity of drugs-like organic compounds are based on the
molecular recognition between the particular atoms of the ligand and the target. Using this concept, we have developed
a consistent system of atom-centred neighbourhoods of atoms descriptors, including MNA (Filimonov et al., 1999), QNA
(Filimonov et al., 2009), and LMNA (Rudik et al., 2014), and have implemented them in several SAR/QSAR/QSPR
modelling approaches [45,46].

2.5.2. РАSS
The concept of the biological activity spectrum was introduced to describe the properties of biologically active
substances. The PASS (prediction of activity spectra for substances) software product, which predicts more than three
hundred pharmacological effects and biochemical mechanisms based on the structural formula of a substance, maybe
efficiently be used to find new targets (mechanisms) for some ligands and, conversely, to reveal new ligands for some
biological targets. We have developed a WWW interface for the PASS software. A WWW server for the online prediction
of the biological activity spectra of substances has been constructed [48,85].

2.5.3. GUSAR
GUSAR software was developed to create QSAR/QSPR models based on the appropriate training sets represented as SD
files containing data about chemical structures and endpoint in quantitative terms. GUSAR has been developed
according to OECD (Organisation for Economic. Co-operation and Development) principles and includes the last
achievements in QSAR modelling: consensus prediction, applicability domain assessment, internal and external models’
validation, and precise interpretations of obtaining results [61,84].

2.5.4. BRENDA
It is the most comprehensive information repository on enzymes and enzyme ligand data. The BRENDA enzyme
information system has developed into an elaborate system of enzyme and enzyme-ligand information obtained from
various sources, combined with flexible query systems and evaluation tools [51,90].

2.5.5. Pharma Expert Software

PharmaExpert determines the existing relationships between pharmacological effects and biochemical mechanisms.
The current version of PharmaExpert covers 1587 mechanisms of action, 418 pharmaco-therapeutical effects and 2664
types of relationships between them. Each biologically active compound reveals various biological actions in biological
systems (human organisms, animals, in vivo and in vitro assays). It is impossible to study each compound in all tests
currently available. Therefore, the ability to select compounds with required types of biological activity and without
unwanted adverse effects and toxicity is very desirable [77,78].

2.5.6. Chemical Checker

It is a resource of chemical and biological small molecule similarities. Molecules are compared from multiple viewpoints
relevant to the drug discovery pipeline, from the chemical properties to the clinical outcomes [37, 65].

2.5.7. Toxtree
Toxtree is a fully featured and flexible, user-friendly open-source application that can estimate toxic hazards using a
decision tree approach. Toxtree could be applied to datasets from various compatible file types. User-defined molecular
structures are also supported – they could be entered by SMILES or the built-in 2D structure diagram editor [74,92].

2.6. Open-Source Cheminformatics toolkits

Open-Source Cheminformatics toolkits are software development kits that allow the development of unique computer
applications for virtual screening and bioinformatics. The toolkits include ADMET predictor, MedChem studio,
MedChem designer and OpenBabel [88].

Strategy to follow is to use keywords from your title in first few sentences

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3. Results and discussion

This from the data reviewed from various authentified journal publications, we found that several bioinformatics tools
are being used for drug design through docking studies. All these software is based on computer simulations and large
databases. By reviewing one by one, it has been noticed that some of them are incredibly useful and precise compared
to others. The consolidated report on these is given as follows:

Table 1 Consolidated report of features of docking software

Docking Auto
Release Open Operating Ligand ADMET 3D
Software score binding site Rating
Year Access System edited properties visualisation
accuracy detection
SeeSAR 2019 No Windows 8 Yes Yes Yes Yes 7
Autodock 1990 Yes Windows 9 Yes Yes Yes Yes 9
Autodock Vina
2018 Yes Windows 9 Yes Yes Yes Yes 9
Extended
Swiss Dock 2011 Yes Windows 7 No No Yes Yes 8
InfiniSee 2019 No Windows 8 Yes Yes Yes Yes 8
Zdock 2010 Yes Windows 6 No No Yes Yes 6
GOLD 1995 No Windows 6 No No Yes Yes 6
Glide 2004 No Windows 7 Yes No Yes Yes 6
FlexAID 2015 Yes Windows 6 No No Yes Yes 5
GEMDOCK 2004 Yes Windows 7 Yes No Yes Yes 7
SeeSAR 2019 No Windows 8 Yes Yes Yes Yes 7
MS-Dock 2008 No Windows 5 No No Yes Yes 5
LigandFit 2003 No Windows 6 Yes No Yes Yes 6
UCSF Dock 1982 Yes Windows 8 Yes Yes Yes Yes 8
GalaxyPepDock 2018 No Windows 5 Yes No Yes Yes 5
Stardrop 2016 No Windows 7 Yes Yes Yes Yes 7
rDock 1998 Yes Windows 5 No No Yes Yes 6
Way2Drug 2016 Yes Windows 7 No No Yes Yes 9
Blaster 2009 Yes Windows 7 No No Yes Yes 5
Haddock 2003 Yes Windows 6 No No Yes Yes 5

4. Conclusion
The present review has shown that several bioinformatics tools are used for drug design through docking studies. For
docking, it has been noticed that a few reliable and high-profile software are available only as commercial versions. To
access these, we need to invest a considerable amount of money annually since they do not provide lifetime access to
any of these paid versions. Apart from all these, only a precise docking result will give perfect biological activity
prediction depending on the flexibility of both the ligand and the target. This can be obtained by dealing with a broad
database and perfect computer simulations. Both these features are found only in a minimal amount of software. Since
it is meant to be used commercially and costs high, it is not familiar among academicians, research scholars, and
students. Therefore, many people are ignorant about the usefulness of these software.

Autodock still has the upper hand among all the bioinformatic tools because of its accuracy and free availability. Its
latest version available is Autodock Vina extended. Several Graphical User Interfaces (GUIs) are available for Autodock

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Vina, making it functional and significantly less time-consuming for the docking process. This programme’s advantage
is that it does not need any language commands now, as in their older versions. It also supports both Windows and Mac
operating systems. The only disadvantage is needing a bit larger disk space to run the programme. Apart from Autodock,
SeeSAR and infiniSee are also high-profile software from BiosolveIT. Next comes UCSF Chimera and PASS because of
their reliability of results. The use of activity prediction and other QSAR studies, the software used are strictly based on
the reliability of its results.

Compliance with ethical standards

Disclosure of conflict of interest

No conflict of interest.

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