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Abstract: The field of drug discovery is
extremely complex and ever changing, with new
methodologies and technologies being introduced
constantly. In the last few years, the most of the work
done in the industries over the last twenty years are
rapidly being replaced by high-throughput methodology in
several scientific areas, including DNA and genomic
sequencing, protein analysis and high throughput
screening for inhibitor compounds. Biotechnology helps
to create novel structures of high-value biomolecules
for use in medicine and industry, through the directed
alteration of proteins and/or biologically active
molecules in living cells to produce a novel
biometabolites. For the development of new drugs by
biotechnology, desired biomolecules have to be
rationally designed based on their structure-activity
relationship, and then screened through well-established
mutation and selection program. Over the past decade,
there has been significant progress in mutation and
selection methodology; DNA shuffling technology
mimicking natural evolution for artificial DNA
recombination and phage-displayed combinatorial peptide
library for rapid selection of proteins expressed from
mutated genes. Bioinformatic tools including functional
genomics and proteomics have been also developed for the
ready access to the information related to the
protein-function and genome-protein, leading to the
design and identification of new drug targets.
Throughout the use of an enormous amount of
bioinformatic databases, many protein/peptide drugs and
biometabolite molecules have been designed. The
candidates of new drugs are monoclonal antibodies,
vaccines, enzymes, antibiotics, therapeutic peptides,
and so on.
The rapid progresses in genetic engineering and the
development of many more new recombinant DNA techniques
have provided us with the capability of design,
modification and engineering of the natural biomolecules.
Major goal of biotechnology, is the design and creation
of novel biomolecular compounds for medicinal and
industrial application, through the directed alteration
of protein biosynthesis in living cells or engineering
of active biomolecules.
To design and alter biologically active biomolecules,
five aspects have to be considered and dealt with:
bioinformatics related to the functional genomics and
proteomics, protein structure-function relationship,
structure-based design, prediction of designed protein
structure, and mutation and selection (Fig.1).
Bioinformatics databases related to functional genomics
and proteomics are now accumulated for ready access to
the information on the genome protein relationship. Some
of three-dimensional structural informations of
biomolecules required for understanding of
structure-stability/structure-activity relationship are
also available as the results of X-ray crystallographic
and NMR studies. The major approach of biotechnology is
oriented to the development of new biomolecules for
medicinal application. The biotechnology based drugs
often require activity and stability in the presence of
enzymes and natural inhibitory compounds, in addition to
the requirement of their efficient delivery to the
targeted cells or tissues, or long acting property in
vivo system without serious side effects.
Bioinformatics and Drug Discovery
Bioinformatics is a theoretical biology that uses
biological data and knowledge stored in computer
databases to derive new biological knowledge. The first
bioinformatics was the structural genomics established
by mapping and sequencing the whole genomes of
organisms. Based on structural genomics, the comparative
genomics appeared for the prediction of protein function
by pair wise sequence to sequence comparison and profile
to profile comparison. In recent days, functional
genomics and proteomics are newly introduced in order to
accumulate the information directly reflecting the
living cells under different states and conditions. Both
functional genomics and proteomics offer abundance of
information on gene expression patterns and phenotypes
of biological system at the different states. Thus those
bioinformatics databases are already making practical
contributions to the target identification and in the
design of the combinatorial libraries, based on
knowledge of one or more protein structures deduced from
the multiple genomic sequences. For instance, those
bioinformatics may yield insight into many of the most
common but not-easily-cured human diseases, such as
diabetes, arthritis, cancers, and Alzheimer’s disease,
where multiple factors, including environmental and
genetic, are considered to be attributable.
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