Surabhi et al Journal of Drug Delivery & Therapeutics.

2018; 8(5):504-509

Available online on 19.09.2018 at http://jddtonline.info

Journal of Drug Delivery and Therapeutics

Open Access to Pharmaceutical and Medical Research
© 2011-18, publisher and licensee JDDT, This is an Open Access article which permits unrestricted
non-commercial use, provided the original work is properly cited

Open Access Review Article

COMPUTER AIDED DRUG DESIGN: AN OVERVIEW
Surabhi1*, B. K. Singh2
1
PG Scholar, Department of Pharmaceutical Sciences, Kumaun University Nainital, India
2
Head & Dean, Department of Pharmaceutical Sciences, Kumaun University Nainital, India

ABSTRACT
Discovery and development of a new drug is generally known as a very complex process which takes a lot of time and resources. So
now a day’s computer aided drug design approaches are used very widely to increase the efficiency of the drug discovery and
development course. Various approaches of CADD are evaluated as promising techniques according to their need, in between all
these structure-based drug design and ligand-based drug design approaches are known as very efficient and powerful techniques in
drug discovery and development. These both methods can be applied with molecular docking to virtual screening for lead
identification and optimization. In the recent times computational tools are widely used in pharmaceutical industries and research
areas to improve effectiveness and efficacy of drug discovery and development pipeline. In this article we give an overview of
computational approaches, which is inventive process of finding novel leads and aid in the process of drug discovery and
development research.
Keywords: computer aided drug discovery, structure-based drug design, ligand-based drug design, virtual screening and molecular
docking.

Article Info: Received 02 Aug, 2018; Review Completed 11 Sep 2018; Accepted 18 Sep 2018; Available online 19 Sep 2018
Cite this article as:
Surabhi, Singh BK, Computer Aided Drug Design: An Overview, Journal of Drug Delivery and Therapeutics. 2018;
8(5):504-509 DOI: http://dx.doi.org/10.22270/jddt.v8i5.1894

*Address for Correspondence:

Surabhi, PG Scholar, Department of Pharmaceutical Sciences, Kumaun University Nainital, India

INTRODUCTION
Computational approaches in drug design, discovery and in terms of time, money and manpower. Generally it is
development process gaining very rapid exploration, found that drug discovery and development process
implementation and admiration.Introducing a new drug takes around 10-14 years and more than 1 billion dollars
in a market is a very complex, risky and costly process capital in total 1.

10,000 250 5
1 Drug
compounds compounds compounds

Drug discovery Preclinical Phase Clinical Phase 1-4 FDA Approved

10-14 years

>1 Billion dollars

Figure 1: Traditional process of drug discovery and development.

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Surabhi et al Journal of Drug Delivery & Therapeutics. 2018; 8(5):504-509

So for reducing time, cost and risk borne factors cost of drug discovery and development up to 50% 2.
computer aided drug design (CADD) method is widely CADD consist use of any software program based
used as a new drug design approach. It has been seen process for establishing a standard to relate activity to
that by the use of CADD approaches we can reduced the structure 3.

Drug
candidate

Figure 2: General Principle for Drug design through CADD.

Major types of approaches in CADD
There are mainly two types of approaches for drug design through CADD is the following:
1. Structure based drug design / direct approach
2. Ligand based drug design / indirect approach

CADD

Structure based Ligand based

drug design drug design

Pharmacophore Quantitative structure

Binding site
modelling activity relationship
identification

Docking
and scoring

Virtual

Screening

Compound Selection

Lead Optimization

New Drug

Figure 3: General Representation of workflow for CADD.

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Surabhi et al Journal of Drug Delivery & Therapeutics. 2018; 8(5):504-509

1. Structure-based drug design calculate after the process of docking; to design a new
drug molecule, which shows better interaction with
In SBDD, structure of the target protein is known and
target protein 4.
interaction or bio-affinity for all tested compounds

- Molecular Docking

- Molecular Dynamics

Design &
synthesis of new
ligands

SBDD

Figure 4: Layout of SBDD 5.

Overview of the process involved in SBDD with the active site of target protein. Top ranked
compounds are tested with biochemical assays.
SBDD runs through multiple cycles before the
optimized lead reached into clinical trials. The first Second cycle comprises structure determination of the
cycle comprises isolation, purification and structure protein in complex with the most optimistic lead of the
determination of the target protein by one of three key first cycle, the one with minimum micro-molar
methods: like X-ray crystallography, homology inhibition in-vitro, and shows sites of the compound
modeling or NMR. Using compounds comes through which can be optimized for further increment in the
virtual screening of different databases are placed into a potency. After several additional cycles like synthesis of
selected region (active site) of the protein. These lead, further optimization of lead through complex
compounds are scored and ranked on the bases of steric, structure of protein with lead compound, the optimized
hydrophobic, electrostatic interaction of these molecules compounds generally show marked increment in the
target specificity and binding affinity 6.

Target Identification& validation

Analyze structure for potential ligand binding sites

Lead Identification& Molecular Docking

Lead Validation &Optimization

Clinical Trials
Figure 5: Steps involved in SBDD.

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Surabhi et al Journal of Drug Delivery & Therapeutics. 2018; 8(5):504-509

2. Ligand-Based drug design target site is known. These ligands can be used to
develop a pharmacophore model or molecule which
In LBDD, 3D structure of the target protein is not known
possesses all necessary structural features for bind to a
but the knowledge of ligands which binds to the desired
target active site.

Figure 6: Outline of process involved in LBDD 7.

Generally ligand-based techniques are pharmacophore based approach and quantitative-structure activity relationships
(QSARs). In LBDD it is assumed that compounds which having similarity in their structure also having the same
biological action and interaction with the target protein 8.
Virtual screening
Virtual screening has been worked as a most convenient tool now a day to find out the most favorable bioactive
compounds with the help of information about the protein target or known active ligands. In the recent time virtual
screening is known as a mind blowing alternative of high-throughput screening mainly in terms of cost effectiveness
and probability of finding most appropriate novel hit through filter the large of libraries of compounds 9.

Figure 7: Overview of Virtual screening process 10.

There are generally two types of virtual screening active site and LBVS method is based on estimation of
approaches like structure-based virtual screening calculated similarity between the known active and
(SBVS) and ligand-based virtual screening (LBVS), compound come from databases.
SBVS method rely on the structure of target protein

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Surabhi et al Journal of Drug Delivery & Therapeutics. 2018; 8(5):504-509

Figure 8: Schematic diagram of VS process for SBDD & LBDD 11

Molecular docking used to accurate estimation of most favorable binding
modes and bio-affinities of ligands with their receptor,
Molecular docking is in-silico method which predicts
presently it has been broadly applied to virtual screening
the placement of small molecules or ligands within the
for the optimization of the lead compounds.
active site of their target protein (receptor). It is mainly

Figure 9: Process of Docking 12

Molecular docking methodology comprises mainly three  It gives compounds with high hit rates through
goals which are interconnected to each other like: searching huge libraries of compounds in silico in
prediction of binding pose, bio affinity and virtual comparison to traditional high throughput screening
16
screening. In the molecular docking method the basis .
tools are search algorithm and scoring functions for  These approaches minimize chances of failures in
creating and analyzing conformations of the ligand 13. the final phase.
ADVANTAGES OF CADD CONCLUSION AND FUTURE ASPECTS
 Through it we can reduce the synthetic and Computer aided drug design is an efficient tool in the
biological testing efforts 14. area of drug discovery and development, through it we
 It gives the most promising drug candidate by can find the most promising drug candidate in a very
eliminate the compounds with undesirable cost-effective way. It always provides a hope for
properties (poor efficacy, poor ADMET etc.) betterment in drug discovery area. In the past years
through in silico filters 15. through Computer aided drug design many impressive
 It is a Cost-effective, time saving, Rapid and researches are achieved so it will play a very much
automatic process. important role in the near future. With the current
 Through it we can know about the drug-receptor achievement’s, there is a promising future of computer
interaction pattern. aided drug design to aid drug discovery of many more
curatives in future.

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Surabhi et al Journal of Drug Delivery & Therapeutics. 2018; 8(5):504-509

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