INTRODUCTION

Researchers are now constantly making efforts to explore the function of the biological system. Efforts are
only at a stage of unprecedented development and growth, expressed in the amount of data produced
from each experiment (Avashthi etal., 2014;).
Via bioinformatics, these huge datasets from the experiments are turned into usable information.
Bioinformatics is recognized as the science of the 21st century and has tremendous potential for decoding
complex biological systems via analysis and integration of multiomics data. It uses information technology
(IT) to allow various types of biological data to be analyzed, linked, and manipulated to understand new
biological insights.
In other words, bioinformatics is a data management and manipulation method for molecular biology,
biochemistry,the health sector, environmental biology, and agriculture, addressing the storage of data
sets, data mining and processing,structural and functional annotations of gene and protein, system
modeling, and drugs’ discovery. It is used to predict the structure and function of a newly examined
protein and protein sequences to create a cluster of similar family sequences and construct phylogenetic
trees for the study of evolutionary relationships (Wang et al., 2005).
Bioinformatics has a very important role to play in agriculture-dependent countries, where it can be used
to boost nutritional content, increase agricultural produce yields, and implant resistance to many biotic
and abiotic stresses (Jayaram and Priyanka, 2010).
For the agricultural science sector, plant and animal genome sequencing should have an enormous yield.
In both the integration and analysis of genomics, transcriptomics, and other high-throughput sequencing
results, bioinformatics plays a vital role, with great potential in redesigning to boost productivity. To
understand the function and interaction of manygenes, there has been a paradigm change from the
single-gene approach (i.e., gene-by-gene approach) (Kumar et al.,2015).
This change has resulted from the discovery that cross-talking of several biomolecules acting in an
interdependent manner and results in any biological answer. As a consequence, several high-throughput
technologies have been developed that offer insight into all the molecules involved in a process (Kumar et
al., 2015)
. Study in the field of genomics has accelerated the process. There is, however, a large difference in the
expression of a trait between the genotype and the phenotype ( Pathak & Singh, 2020). Studies are
performed at various levels to fill this gap: the whole system, organism, biochemical, gene, and protein
levels. All these fields have contributed to the collection of vast amounts of biological knowledge due to
unprecedented research efforts. Bioinformatics, which culminates in biology andcomputational
technology, aims to develop novel strategies for wide-scale analysis of biological system
Bioinformatics techniques, such as simulation, docking, protein–protein interaction, and analysis of next-
generation sequencing (NGS) data, may be used to investigate or modify the sequence for better fitting of
essential genes for a particularvfunction and to study the function of these genes or proteins at the system
level. It was then possible to use this specified genetic, genomic, and proteomic information to grow
resistant, nutritionally improved, and profitable crops and also discover therapeutic drugs (Allaby and
woodwark,2020; )

Concept behind bioinformatics, in silico biology, and computational biology

There are many definitions are available for bioinformatics in different books and the Internet. We can say
that “Decoding problems arising in the field of biological sciences via computation” is known as
bioinformatics. It handles biological data obtained through several experimental techniques for their
documentation in the form of databases for further availability to the scientific community. This dataset is
analyzed for dissecting the complexity of biological systems, and acquiredknowledge accelerates research
activity and helps scientists to get fruitful results and novel insight. The term “in silicobiology” is
concerned with bioinformatics. Generally, we can say that performing any work using a computer for
biology is known as in silico biology, for example, retrieval of biological sequences from databases.
Computational biology is different from bioinformatics and in silico biology. Here, we are talking about the
development of algorithms and theoretical methods for solving biological problems. These developed
algorithms and methods are
further utilized in the design and development of biological software or tools that help in analyzing
biological data using the computer to create knowledge, that is, bioinformatics. Therefore these disciplines
are linked to each other and use several disciplines of biology and natural sciences along with the
computer, IT, mathematics, and statistics. That is why it is called interdisciplinary science. (Pathak et Al
2018)

Scientific discipline and support systems for bioinformatics

Bioinformatics is a central discipline that is linked with several disciplines of science. These disciplines of
science and
technology provide infrastructure and interdisciplinary nature to bioinformatics. In the sciences discipline,
several traditional and advanced subjects are associated with bioinformatics, such as plant sciences,
animal sciences, molecular biology, genetics, and evolutionary biology, pharmaceuticals, mathematical,
and statistical sciences, and omics. Besides, in the support system, bioinformatics is closely associated with
computer science, IT, and computational resources because theywork as a backbone for bioinformatics.
Therefore these scientific disciplines and support systems are combined to build a new discipline called
bioinformatics for decoding intricate problems linked to biological systems via innovative manner with fast
processing due to the involvement of computer science and IT .

Needs of bioinformatics
Bioinformatics is a need of time because due to advances in several omics platforms have produced big
data in biology related to genomes, transcriptomes, genotyping by sequencing, proteome, metabolome,
etc. The management and analysis of these high-throughput data need bioinformatics. In the era of omics
and availability of organism and discipline/subject-specific data, that is, genomic data, proteomic data,
etc., there is a need to develop specific databases for their documentation.
This will further accelerate the research and help scientists to integrate these available data with novel
discoveries. Besides,these datasets will help in improving the accuracy of available tools and enable
scientists to trained data for the development of new tools via machine and deep learning approaches.
Thus in view of the above facts and contiguous process of experimental data generation needs
bioinformatics professionals to manage and analyze these big data of biology to boosting research and
development in a smart way for mining.

Aim of bioinformatics
As we know that bioinformatics is a need of time in the era of omics, you do not think about research
without bioinformatics or it is necessary for finding new information. The aim of bioinformatics-related
projects is generally
• Documentation of useful information about medicinal plants available in literature/public domains in the
form of a
database.
• Documentation of available information about plants and animal genetic resources.
• Development of useful organism/species-based databases for the documentation of omics data.
• Improvement of the contents and usefulness of already developed/available databases.
• Development of better and fast graphical user interface (GUI)-based tools for data integration and
analysis.
• Improvement of available tool/software for biologist/wet lab scientists/noncomputer background
scientists for their effortless use.
• Development of platform-independent software’s for the computational analysis of biological data.

The recent development in the field of bioinformatics

To understand the code of life that is DNA, bioinformatics has developed and contributed to the growth of
research projectsassociated with high-throughput DNA sequencing and other fields of biology. Its ultimate
aim is to visualize the wealth of biological knowledge hidden in sequences, structures, literature, and
other big data of biology. In the era of omics, the use of computational tools becomes necessary for the
investigation of useful information from large sets of biological data. The analysis of these data required
good bioinformatics skills and most biologists are not familiar with command-line tools, bioinformatics
analysis, and interpretation. Therefore much collaboration has been established among experimental
biologists and bioinformatics groups to make their data meaningful. Now in recent years, several GUI-
based software platformshave been developed that can easily understandable for biologists to integrate
and analyze high-throughput omics data.
Bioinformatics has evolved into a full stream of multiple opportunities for researchers from different
areas, such as medicine, biotechnology, plant breeding, chemistry, statistics, mathematics, computer
sciences, and IT. The main motto of this field is to turn data into knowledge through computation. With
the advancement of many other significant research areas, such as systems biology, synthetic biology,
nanotechnology, and pharmacogenomics, it is still growing. Due to advances in technology and data
accumulation at an unprecedented rate, bioinformaticians are expected to be in constant demand to
decode the complexity of data for addressing the biological problem (hogeweg,,2011).

Challenges in bioinformatics
Different disciplines of science and technology are associated with bioinformatics. This association is also a
challenge to understand the subject due to its interdisciplinary nature for the peoples in different
backgrounds, for example, people with biology background generally facing problem with computer and
people from computer science background facing some problem with the concept of biology. Therefore
bioinformatics gained importance in recent years as compulsory courses for many postgraduate programs
run by universities in different disciplines of science and technology to trained students in this area. The
major challenges in the area of bioinformatics faced by scientists from biology background are:
• Design of small drug-like molecule,
• Development of a quantitative model for signal transduction pathway,
• Accurate prediction of protein secondary and tertiary structure using amino acid sequence,
• Understanding the evolution of protein,
• Understanding the speciation event,
• Understanding gene ontology,
Besides, there are many challenges faced by computer scientists working in the area of bioinformatics,
such as:
• Management of big data in biology,
• Information management,
• Improve the accuracy of software, and
• Programmability.
Therefore it is an urgent need to develop manpower in this emerging field, they know about biology and
computer along
with associated disciplines/subjects for solving complex problems in biology (Moussa et al., 2016).
This will ultimately accelerate the outcome of the research projects but developing interest in computer
science/programming to the biology students and in biology to the computer science/mathematics
students is also a common challenge right
now. Due to dependency on the computer for every work, it may be solved by the near future.

Application of bioinformatics
Bioinformatics has great potential to solve complex problems in biology and associated disciplines. With
the start of thehuman genome project, it becomes an essential tool for scientists and playing a key role in
the area of life sciences, chemical sciences, physical sciences, agricultural sciences, and medical sciences.
Some important applications of bioinformatics are discussed in the following sections.

Sequence analysis
Sequence analysis is one of the major applications of bioinformatics with the development of the Basic
Local Alignment Search Tool (BLAST) program in 1990 and has become popular. The area of sequence
analysis is very broad; here, we
analyze the nucleotide or protein sequence of any organism for several purposes. Here, we can analyze
single or multiple sequences to find out similarity and identity among them via several sequence
alignment tools, such as BLAST and FASTA Clustal. It is also used in the annotation of newly discovered
sequences, find out conserved regions, and other regulatory regions among them. Besides, the prediction
of the physicochemical properties of sequences also comes under the sequence analysis (Chinchole,et Al
2017).

Phylogenetic analysis
Phylogenetic analysis is another important research area in bioinformatics. Here, we can visualize the
evolutionary event and construct a relationship among organisms or sequences. It is extensively used in
evolutionary biology for the objective of determining the evolutionary event via multiple sequence
alignment followed by tree construction. It also supports the identification of key regions within
sequences and plays an important role in vaccine and drug designing programs etc.

Prediction of protein secondary structure

Right now, three computational methods, that is, Chau Fasman, GOR, and PHD, are available for protein
secondary structure prediction. As it is a key area of the structure in the field of structural bioinformatics,
various computational algorithms have been developed and used. Artificial Neural Network and Hidden
Markov Model are the commonly used methods for the different available software. The secondary
structure prediction methods are generally used to determine the number of amino acid residues involved
in the formation of different types of secondary structures, that is, which or how many amino acid
residues are involved in the formation of the helix, strand, coil, and turn. It provides support in the
building of the 3D structure of a protein based on secondary structure information when a suitable
structural homolog is not available in the protein data bank (Pathak,et Al 2020).

Protein 3D structure prediction

Prediction of protein 3D structure from sequence information is a challenging task in bioinformatics for
the quality of
the model. Right now three computational approaches are used, that is, homology or comparative
modeling, threading or fold-recognition, and ab initio. It plays a crucial role when the experimentally
determined structure of the target protein is not available in the PDB database. It is used to determine the
structure of newly discovered proteins or other proteins their structures are not solved by NMR or X-ray
crystallography for ligand small molecule screening for identification of lead molecules for
drugs/agrochemicals development. Besides, modeled structures are utilized for predicting protein–protein
interactions, structural comparison, alignment, etc., for new insight via computation.

Evaluation and validation of predicted protein model

Various computational methods are developed by bioinformatics scientists for the quality analysis and
validation of the
predicted protein 3D model. The most popular program used for evaluation and model validation is Swiss
PDB viewer,
structural analysis and verification server (SAVES), Rampage, and PROCHECK. We can evaluate and refined
our predicted model with the help of the above tools for further investigation (Mamgain, 2015).

Discovery and designing of small molecules leading to drugs/agrochemical development

Bioinformatics plays a vital role in the discovery of lead molecules. Techniques, such as molecular docking,
virtual screening, and molecular dynamics simulation, are widely used for this purpose .With the help of
molecular docking and virtual screening, we can identify novel molecules for the treatment and
prevention of diseases in humans, animals, and plants (Pathak et al.,2020).
Furthermore, it can be validated in terms of conformational behavior and stability during target–ligand
interaction withr espect to time using a molecular dynamics simulation study (. This study helps in the
identification of lead compound quickly with the help of computational tools and reduced the time and
experimental cost, the fast drug discovery process for downstream validation.

Next-generation sequencing data analysis

Due to progress and recent development in several omics platforms and various sequencing technologies,
a big amount of data has been generated every day that need bioinformatics for their analysis and
management. In recent years a bunch of tools and databases has been developed for the management,
integration, and analysis of such big data. These tools are useful in the identification of differentially
expressed genes via analysis of microarray and RNAseq/transcriptome data, assembly and annotation of
genome and transcriptome, SNP discovery, genome-wide association study, identification and
characterization of gene families, the discovery of new genes, etc. The obtained information from big data
analysis will help in different research programs associated with plant and animal breeding, marker
development, drug target identification, and drug discovery.

1.6.8 SNP and SSR identification

Progress in NGS and bioinformatics has enabled the large-scale discovery of SNP and SSR markers. It has
revolutionized research related to genomics and assists in the molecular breeding program, and it will also
help in analyzing geneticndiversity and population structure, designing genetic maps of high density, and
providing genotypes for genome-wide association research.

1.6.9 Pharmacogenomics
In the postgenomic era, pharmacogenomics is recognized as one of the keys and highly demanded
research areas to study the response of a drug based on genetic variants for the development of
personalized medicine. As we know that some drugs are working on a particular population and or group
of peoples but no desired response of these drugs was reported in other populations or countries due to
minute change in genomic regions. So that the concept of pharmacogenomics has been introduced for the
development of a person or population or area-specific medicine to reduce the risk of side effect and
increase their potency. Therefore bioinformatics tools are rapidly utilized for the analysis of high-
throughput genomics data for the detection of how genes alter the response of a drug; this investigation
will lead to the development of personalized medicine (Aneesh, Sekhar, Jose, Chandran, & Zachariah,
2009; Takahashi, Luzum, Nicol, & Jacobson,

PLANT BASED COMPOUNDS FOR CANCER TREATMENT

Plants have a long history of use in the treatment of cancer. Hartwell, in his review of plants used against
cancer, lists more than 3000 plant species that have reportedly been used in the treatment of cancer. In
many instances, however, the “cancer” is undefined, or reference is made to conditions such as “hard
swellings”, abscesses, calluses, corns, warts, polyps, or tumors, to name a few. These symptoms would
generally apply to skin, “tangible”, or visible conditions, and may indeed sometimes correspond to a
cancerous condition. Many of the claims for efficacy in the treatment of cancer, however, should be
viewed with some skepticism because cancer, as a specific disease entity, is likely to be poorly defined in
terms of folklore and traditional medicine. This is in contrast to other plant-based therapies used in
traditional medicine for the treatment of afflictions such as malaria and pain, which are more easily
defined, and where the diseases are often prevalent in the regions where traditional medicine systems are
extensively used. However, despite these observations, it is significant that over60% of currently used anti-
cancer agents are derived in one way or another from natural sources, including plants, marine organisms
and micro-organisms. Indeed, molecules derived from natural sources (so-called natural products),
including plants, marine organisms and micro-organisms, have played, and continue to play, a dominant
role in the discovery of leads for the development of conventional drugs for the treatment of most human
diseases.
The search for anti-cancer agents from plant sources started in earnest in the 1950s with the discovery
and development of the vinca alkaloids, vinblastine and vincristine, and the isolation of the cytotoxic
podophyllotoxins. These discoveries prompted the United States National Cancer Institute (NCI) to initiate
an extensive plant collection program in 1960, focused mainly in temperate regions. This led to the
discovery of many novel chemotypes showing a range of cytotoxic activities, including the taxanes and
camptothecins, but their development into clinically active agents spanned a period of some 30 years,
from the early 1960s to the 1990s. This plant collection program was terminated in 1982, but with the
development of new screening technologies, the NCI revived the collections of plants and other organisms
in 1986. (Siriwantanmetanon et Al 2010).

CANCER
Globally cancer is a disease which severely effects the human population. There is a constant demand for
new therapies to treat and prevent this life-threatening disease. Scientific and research interest is drawing
its attention towards naturally-derived compounds as they are considered to have less toxic side effects
compared to current treatments such as chemotherapy. The Plant Kingdom produces naturally occurring
secondary metabolites which are being investigated for their anticancer activities leading to the
development of new clinical drugs. With the success of these compounds that have been developed into
staple drugs for cancer treatment new technologies are emerging to develop the area further. New
technologies include nanoparticles for nano-medicines which aim to enhance anticancer activities of
plant-derived drugs by controlling the release of the compound and investigating new methods for
administration. This review discusses the demand for naturally-derived compounds from medicinal plants
and their properties which make them targets for potential anticancer treatments. Cancer has been a
constant battle globally with a lot of development in cures and preventative therapies. The disease is
characterised by cells in the human body continually multiplying with the inability to be controlled or
stopped. Consequently, forming tumours of malignant cells with the potential to be metastatic (ochwang
et Al 2014).
Current treatments include chemotherapy, radiotherapy and chemically derived drugs. Treatments such as
chemotherapy can put patients under a lot of strain and further damage their health. Therefore, there is a
focus on using alternative treatments and therapies against cancer
For many years herbal medicines have been used and are still used in developing countries as the primary
source of medical treatment. Plants have been used in medicine for their natural antiseptic properties.
Thus, research has developed into investigating the potential properties and uses of terrestrial plants
extracts for the preparation of potential nanomaterial based drugs for diseases including cancer 3. Many
plant species are already being used to treat or prevent development of cancer. Multiple researchers have
identified species of plants that have demonstrated anticancer properties with a lot of focus on those that
have been used in herbal medicine in developing countries.(Freiburghaus et Al 2013).
Compounds which are characteristic to the plant kingdom and are necessary for plant survival and
“housekeeping” of the organism are being investigated for their ability to inhibit growth and initiate
apoptosis of cancerous cells. This article aims to take an overview of current plant derived compounds
that have anticancer therapeutic properties and their developments in the field.

Epigenetic properties
The step towards development of cancer involves alterations of epigenetic processes and their
deregulation 9.The control of hypermethylation of tumour-suppressor genes on CpG islands is deregulated
in cancer cells. This can result in gene silencing and inactivation of tumour-suppressor genes Drugs which
can inhibit or reverse epigenetic alterations have been in development over recent years.(schnekenburger
et Al 2014).
Chemically derived epigenetic drugs have been developed and undergone trials such as 5-azacytidine
(azacitidine; Vidaza) and 5-aza-2’-deoxycytidine (decitbine; Dacogen) which are both DNMTi 11 and HDACi
such as suberoyanilde hydroxamic acid (SAHA, Vorinostat, Zolinza) and FK228 (Romidespin, Istodax) 9.
However, it is difficult to engineer a chemically derived drug which is non-toxic to normal cells and is
specific to cytotoxicity of cancer cells. Therefore, development and research into naturally derived
compounds to be used for anticancer treatment is becoming high in demand with a focus on those
derived from plant species and their natural products.

There are many forms of cancer amongst the human population but they share similar characteristics or
genotypes such as insensitivity to signals which inhibit cell growth making their replication limitless.
Apoptosis is evaded and never induced in cancer cells and angiogenesis is sustained within the tumour
tissue allowing survival of cancer cells. Plant derived compounds have demonstrated properties to inhibit
cancer cell activity such as inhibiting proliferation of cancer cells and inducing apoptotic cell death.

Plant compounds with anticancer properties

Medicinal plants have been used for thousands of years in folk medicines in Asian and African populations
and many plants are consumed for their health benefits in developed nations. According to the World
Health Organisation (WHO) some nations still reply of plant-based treatment as their main source of
medicine and developing nations are utilising the benefits of naturally sourced compounds for therapeutic
purposes 13. Compounds which have been identified and extracted from terrestrial plants for their
anticancer properties include polyphenols, brassinosteroids and taxols.
a. Polyphenols
Polyphenolic compounds include flavonoids, tannins, curcumin, resveratrol and gallacatechins and are all
considered to be anticancer compounds . Resveratrol can be found in foods including peanuts and grapes
and red wine. Gallacatechins are present in green tea. It is thought including polyphenols in a person’s diet
can improve health and reduce risk of cancers by being natural antioxidants (Azmi et al 2010).

The cytotoxicity of polyphenols on a range of cancer cells has been demonstrated and their antioxidant
properties determined. Polyphenols are thought to have apoptosis inducing properties showing anticancer
properties which can be utilized. The mechanism in which polyphenols are thought to carry out apoptosis
initiation is through regulating the mobilization of copper ions which are bound to chromatin inducing
DNA fragmentation. In the presence of Cu(II), resveratrol was seen to be capable of DNA degradation.
Other properties plant polyphenols show is their ability to interfere with proteins which are present in
cancer cells and promoting their growth. Cancer agents may be altered through the polyphenol regulating
acetylation, methylation or phosphorylation by direct bonding. For example, curcumin treated cancer cells
in various cells lines have shown suppression of the Tumour Necrosis Factor (TNF) expression through
interaction with various stimuli

b. Flavonoids
Flavonoids are from the polyphenolic compounds and constitute a large family of plant secondary
metabolites with 10,000 known structures 19. They are physiologically active agents in plants and
becoming of high interest scientifically for their health benefits .
Various plants have been investigated for their flavonoid content and how these compounds affect cancer
cells, such as fern species and plants used in traditional Chinese medicines like the litchi leaf . There is a
high content of flavonoid compounds such as anthocyanins, flavones, flavonols, chalcones and many more
which can be found in just one structure of the plant like its seed . identified and looked at the anticancer
effects of flavonoids on human lung cancer cells (A456 cell line) from the fern species Dryopteris
erythrosora. They found flavonoids to demonstrate cytotoxicity on cancer cells and to have high free
radical scavenging activity . Purified flavonoids have also shown anticancer activities against other human
cancers including; hepatoma (Hep-G2), cervical carcinoma (Hela) and breast cancer (MCF-7) . The
flavonoids extracted from Erythrina suberosa stem bark (4’-Methoxy licoflavanone (MLF) and Alpinumi
soflavone (AIF)) were shown to have cytotoxic effects in HL-60 cells (human leukaemia) . MLF and AIF
induced apoptosis through intrinsic and extrinsic signalling pathways. The mitochondrial membrane
potential is significantly reduced due to the induction of apoptotic proteins. With mitochondria damage to
cells the cancer cells cannot survive. Other studies have looked at flavonoid extracts from fern species and
found that even in low concentrations they still demonstrate high percentage of anticancer activity .
As previously mentioned polyphenols can inhibit or alter the regulation of proteins and other agents
which may be contributing to the survival of cancer cells. Signal Transducer and Activator of Transcription
(STAT) proteins are anti-apoptotic and contribute to cancer cell growth. MLF and AIF inhibit members of
this family of proteins by preventing their phosphorylation needed for the cancer cells survival. Also, these
flavonoids inhibit the expression of NF-κB which is needed for cancer cell survival and angiogenesis and
proliferation.

ROLE OF BIOINFORMATICS IN DRUG DISCOVERY

The drug discovery process was beginning in 19th century by John Langley in 1905 when he proposed the
theory of respective substances. The first rational development of synthetic drugs was carried out by Paul
Ehrlich (father of modern chemotherapy) and SacachiroHata who produced arsphenamine(Salvarsan) in
1910 by structure activity relationship from atoxyl used in sleeping sickness (trypanosomiasis) and
syphilis .Drug discovery is the stepby-step process by which new candidate drugs are discovered. Normally,
pharmaceutical companies follow well-established pharmacology and chemistry-based drugdiscovery
approaches, and face various difficulties in finding new drugs .The aim of drug discovery is to produce
more and more drugs in a short period of time with low risk in bioinformatics In fact, now there is an
existence of new, separate field, known as computer aided drug design (CADD).(A cm song et al.2009).
The drug discovery process can be described as the identification and validation of a disease target and
the discovery and development of a chemical compound to interact with that target .Pharmaceutical
industry need multidisciplinary informatics systems such as
High Throughput Screening(HTS) data,
Computational Chemistry,
Combinatorial Chemistry,
ADME Informatics,
Cheminformatics,
Toxicology,
Metabolic Modeling,
Bioinformatics in medical substance, Drug Discovery and Metabolism and so on. Information way in and
news between different departments like the development and discovery (y.p Chen.et Al 2008).

DRUG TARGET IDENTIFICATION

The current approach is to identify the biologically activecandidates. Drugs are usually only developed
when the particular drug target for those drugs‟ actions have been identified and studied. The number of
potential targets for drug discovery process is increasing exponentially. Mining and warehousing of the
human genome sequence using bioinformatics has helped to define and classify the nucleotide
compositions of those genes, which are responsible for the coding of target proteins, in addition to
identifying new targets that offer more potential for new drug .This is anarea where the human genome
information is expected to play a master role [12]. Drug developers developed the unnatural good quality
of more genes are identified and the drug discovery cycle becomes more data-intensive.
Bioinformatics is used to identify and analyse more and morebiological drug targets; thus expected to
greatly increase the breath of possible drugs in the pipelines of pharmaceutical companies.(M.Loh 2011).

DRUG TARGET VALIDATION

Bioinformatics also provides strategies and algorithm to predict new drug targets and to store and control
available drug target information. After the discovery of „„potential‟‟ drug targets, there is an insignificant
need to establish a strongassociation between a putative target and disease of interest.The establishment
of such a key association provides justification for the drug improvement process this process is known as
target validation. It is an area where bioinformatics play a vital role. The possibility for failure in the clinical
testing and approval phases can be moderated by Drug target validation.(E.A martis.2011).

HIT TO LEAD SELECTION

Drug discovery involves different phases from target identification to preclinical development. In modern
drug discovery involves the process of transforming small molecules of protein function into high content
lead activities .Most commonly hit compounds are derived by High Throughput Screening (HTS). HTS a
high-tech approach for drug discovery in current trend to show how selective the compounds are for the
chosen target and it is more and more gaining popularity among industrial Researchers.This program have
the potential to screen 10,000 compounds per day, while Ultra High throughput Screening (UHTS) can
screen upto 100,000 assays per day Recently, techniques like Particle Count Measurements for varying
sample concentration, 2D fluorescence intensity distribution analysis for fluorescence interference or color
quenching corrections in scintillation proximity assays (SPAs) have been proposed to eliminate some
artifacts[19].Lead Optimization It follows the lead finding process. The lead aim to synthesize lead
compounds, new analogs with improved potency. Reduce of target activities, and to optimize lead with
other properties such as Selectivity, metabolic stability, etc.
This optimization is proficient through chemical modification of the hit structure, with modifications
chosen by employing structure-activity analysis (SAR) as well as structure based design if structural
information about the target is available [8].The lead compound should have a good drug likeness and
would not interfere with the cytochrome P450 enzymes or with the P-glycoprotein.(p.katara et al 2011).

Drug Development
Once a new chemical was identity and discovered it has to be subjected to the development process.The
ability of chemical is mostly carried out in the R & D divisions of thepharma companies. The structure
activity relationships (SAR) are determined. The compounds are divided into two stages –
preclinical pharmacology (animal studies) and clinical pharmacology (human studies).

Preclinical Studies
The candidate drug is subjected to extensive pharmacological testing invitro and invivo on animal models
(mice, rats, pigs, dogs). Major areas of research are:Acute, subacute and chronic toxicity studies (toxicity
profile) Therapeutic index (safety and efficacy evolution): it is the ratio of median effective
dose(ED50).Absorption, distribution, metabolism &elimination ADME studies (pharmacokinetics)

Clinical Studies
Clinicalstudiesdetermine the metabolic and pharmacologic activity of the drug in humans, side effects due
to increasing the normal dose to higher doses, to gain early evidence on efficacy. About 90% of drug
candidate entering into clinical trials were failed. In 1991, the main reason for failure was problems in
PK/bioavailability (40%) followed by lack of efficacy(30%) and toxicology(12%). In 2000, the main reason
for failure was lack of efficacy (27%), followed by commercial and market reasons (21%).(y yamanishi et al
2010).
There are four phases of clinical trials.
Phase 1: Clnical Phramacology Evolution
Phase 2: Controlled Clinical Evolution
Phase 3: Extended Clinical Evolution
Phase 4: Surveillance During Post Marketing General

Clinical Use
Recent techniques in bioinformatics in drug discovery includes Computer-aided drug design (CADD).
Computer aided drug design is a method to simulate drug receptor
interactions. CADD methods are dependent on bioinformatics tools, applications and databases. There are
several key areas in bioinformatics regarding CADD research.
Bioinformatics techniques are used in two different phases of drug discovery to extract interesting
information and find important genes and proteins speeding the process of drug discovery, this method
gives the accuracy of analysis and its cost is low. Gene identification is a very fundamental and important
technique among them.

CONCLUSION
In recent years bioinformatics has become an essential subject and hot research topic that is associated
with several discipline and methodology. The present chapter highlights the power of bioinformatics and
its approaches for solving a complex biological problem, which leads to research and development.
Besides, it presents several important database resources and tools along with their uses and availability.
In the future, rapid advancement in the generation of big data through omics and other advancements in
different areas are expected in which bioinformatics provide a broad range of applications for their
management, analysis, and novel discovery. Furthermore, this chapter provides career opportunities to
students and researchers in the area of computational and integrated science, that is, bioinformatics.
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