2015 International Conference on Soft Computing Techniques and Implementations- (ICSCTI)
Department of ECE, FET, MRIU, Faridabad, India, Oct 8-10, 2015
Applications of Bioinformatics tools to Combat
the Antibiotic Resistance
Hemlata and Archana Tiwari
Centre for Research Studies, Noida International University, Gautam Budh Nagar, India
E-mail address: panarchana @gmail.com
Abstract -Antibiotic drug resistance is a serious concern world
wide. Antibiotics impose selective pressure in spread of resistance
genes through exchange of genetic material among bacterial
isolates. Addition and excessive use of antibacterial compounds
has changed in the microbial populations of the soil, water and
our own micro biota. Antibiotic resistance makes us helpless.
Now it is the need of era to develop new classes of drugs. But the
field of Bioinformatics revolutionize and fascinating the world of
science and technology. Now a day’s homology modeling
technique used to generate 3D structures to evaluate or justify
our desirable results. Bioinformatics change the face of
molecular studies as to determine the protein structure, gene
structure or sequence, molecular markers and relate them to
other previously known structures. Bio informatics studies have
provided fundamental ways of modeling a biological living cell
system and docking proteins that enabled scientists to discover
effective drug strategies to combat the diversifying problem of
antibiotic resistance among the common casuals of infectious
diseases. The field of bioinformatics has involved most pressing
task such as the analysis and interpretation of various types of
data that includes nucleotide and amino acid sequences, protein
domains, protein structures and clear the behavior of protein-
ligand interaction at molecular level. The criteria of analyzing
the biological annotations or data is referred to as homology
modeling or computational biology
Keywords-Antibiotic resistance, selective pressure, bioinformatics,
computational modeling and docking.
I. INTRODUCTION
In the present day scenario, antibiotics have contributed
much towards the acquisition and spread of resistance genes
via, bacterial reproductive methods among bacterial isolates.
Horizontal gene transfer is the basis of phylogenetic studies
[1] and 16s r-DNA is the widely used approach which relate
the evolutionary history or biological origin of various
bacteria. The rate of bacterial infection and mortality are
under control in 1940s because of wonder drug miracles, but
excessive and unauthorized prescription play a major role in
selective pressure. Hence result in antibiotic resistance. As the
antibiotic resistance rise up the demand of antibiotics also
increases and it consumption level is highly uplifted in 2010
[2].
Antibiotic is referring as any organic substance has
bactericidal or bacteriostatic activity that triggers different
target sites of bacterial cell. Antibiotic resistance problem is
solved with the contribution and collaboration of all applied
978-1-4673-6792-9/15/$31.00©2015 IEEE
bioscience disciplines.By doing so different data or
information are annotated and we present a better health
management. Protein structures can be modeled either ab
initio from sequence alone or by comparative methods that
rely on a database of known protein structures. Currently, in
silico studies have provided fundamental ways of modeling a
biological living cell system and docking proteins that enabled
scientists to discover effective drug strategies to combat the
diversifying problem of antibiotic resistance among the
common casuals of infectious diseases. Bioinformatics play a
vital role in medical research its fascinating results
revolutionize the techniques of treatment.
II.WHAT IS ANTIMICROBIAL RESISTANCE?
We are on back foot and facing revised history of
antibiotic resistance after several years of advancement of
science and technology.
Now we have to again concrete thinking about to control
this emerging problem and sometimes it is impossible to treat
as we are seeing in case of multidrug-resistant strains of
Tuberculosis, also focused in WHO report 2013[3]. Extended
spectrum beta lactamases (ESBL) become the global
headache. ESBL presently detected in domestic animals
through manure dissemination and in food products. In
directly resistance problem occurs in food web ultimately it
show bio-magnification[4–6].Survival of the fittest is -
absolutely proved true by bacterial community in relation of
antibiotics.
Now homology modeling and docking tools with
molecular studies provide a new plate form to the scientist to
design new inhibitors which help in solving the emerging
problems of antibiotic resistance. Wet lab studies and
computational studies now become complimentary to each
other and their results fascinating the world. Their combine
effect proves boons for pharmaceutical companies.
III. APPLICATIONS OF BIOINFORMATICS TOOLS
The panoramic results of Bioinformatics change the
present scenario of medical technologies. It reveals the
miracles of the drugs or inhibitor and revolutionized
pharmaceutical companies. Proteins perform many of the
biological functions on other hand DNA carry genetic
information. Homology modeling produces 3D structures for
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proteins, enzymes or gene also. An application of
computational modeling determines the 3-Dimensional
models of macromolecules, which provide necessary
information about the different parameters involves in the
structure development.
Swiss-Model
This online free software used in homology modeling or
comparative modeling. Fully automated server SWISS-
MODEL has been used to generate reliable model for protein
structure modeling. The template library provides the huge
collection of previously generated or submitted data of
biomolecules and different organic molecules; provide the
base of information to generate our desirable structure. The
reliability and validity of the developed structure by SWISS-
MODEL is governed by PROCHECK system. Homology
modeling comprised of following sequence wise steps-
Fold assignment- It searches for the other related
structures have highest homology to our desired target
sequence.
Target– template alignment- Our desired primary
sequence whose structure has to be generated is known as
target. Template is the previously determined structure of a
query. Hence we have to compare both target-template, hence
named as Target– template alignment.
Model building- After performing Target– template
alignment and by utilizing various algorithms a 3D model is
generate it is known as Model building.
Model assessment-It is the last step of modeling which
determine the accuracy and reliability of generated structure.
To predict protein structure by comparative modeling,
two conditions have to mandatory [9, 10].
1. The primary desired sequence whose structure has
to be generating (the target sequence) must have considerable
similarity to another sequence of known structure (the
template).
2. It is more important to create a perfect and accurate
homology between Target-template, which is the base of
model generation. Keep in mind there should be no alignment
error.
When we do not get the positive assessment (result) of the
model or not desirable, then the model can be rebuilt by
selecting different templates, refining the target–template
alignment, or changing model-building parameters.
Autodock
Docking is applied to govern the molecular aspect of
modeled structure formed by the union of two molecules. The
two biomolecule may be proteins, protein-ligand, DNA-
protein and DNA-ligand-complexes.
Docking experiments can suggests inhibitors for specific
target proteins and thus to design new drugs.The formation of
molecular complexes is the pioneer information concerned
with the vital process of the cell or an organism. Hence reveal
its mechanism of the action. Depend on the nature of dock
molecules. Docking is of following types-
• Protein - ligand-docking- This type of docking
involves protein molecule and ligand. It is the pioneer process
of living system.
• Protein - protein-docking- This type of docking
involves two or more protein molecules. It is also known as
protein-protein interactions (PPIs).
• DNA-protein-docking - This type of docking
involves binding of DNA or gene with protein. Hence
complex control the biological activities.
• DNA-ligand-complexes– This type of docking
involvesbinding of DNA with ligand, form complex.
Sometimes ligand/change or alter the Translation. Hence
affect function of a protein.
¾ A ligand is an organic molecule that make complex
with biomolecules and have the tendency to produce
conformational changes (change in shape ).
AutoDock software follow Monte Carlo simulated
annealing; is a computational method which describes
quantitative studies. It also describes all possible probability
of giving input. Lamarckian genetic algorithm is a toolin
automated dockingmode, generate the results of docked
molecules for flexible ligands. Peter Kollman developed
Assisted Model Building with Energy Refinement, commonly
known as AMBER. It provides limited number of atoms and
calculates atomic charges. AutoDock provides free academic
license. (AutoDock launches its several versions all are free).
Inhibitors have low molecular weight, form complex with
biomolecules and causes conformational changes in complex
biomolecule. These structures provide raw information to
pharmaceutical companies to generate better drugs. Present
time it is necessary to know the function and role of the
proteins in organism for its physical activities, biochemical as
well as biophysical processes carry out in living cell such as
metabolic processes, gene expression, cell physiology, ions
transport, cell signaling and different energy conversion
processes.
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 [9] Marti-Renom, M. A., Stuart, A., Fiser, A.,et al. Comparative protein
structuremodeling of genes and genomes. Annu. Rev. Biophys. Biomol.
Struct; 2000;29, 291–325.
Valuable outcomes [10] Blundell, T. L., Sibanda, B. L., Sternberg, M. J., and Thornton, J. M.
Knowledge based prediction of protein structures and the design of
The outcome of this applied work of bioinformatics and novel molecules. Nature; 1987; 326,347–352.
molecular studies will help us in determining the structure of
MDR organism. The study of its interaction with antibiotics or
inhibitor or organic molecule will help us to identify amino
acid residues crucial to their interactions. This information
will further help us in making improved antibiotics which
provide important information for pharmaceutical companies.
In turn companies discover better antimicrobial agents and
present better health assets.

IV. CONCLUSION

In this paper we focus on the multidrug resistance

problem (MDR) which is a globally accepted challenge still
great progress has been made over the last few years but
certain limitations still exist that hinder the widespread use of
computational models for microbiology research.The synergic
effect of bioinformatics and molecular research will prove
more effective to solve the global headache of MDR or
antibiotic resistance. It enables us to fight against or to resist
MDR infections.

ACKNOWLEDGEMENT

I would like to express my heartiest gratitude to my

colleagues. They inspired and advised me in completion of
this paper.

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