International Journal of Theoretical & Applied Sciences, 14(1): 61-67(2022)

ISSN No. (Print): 0975-1718

ISSN No. (Online): 2249-3247

Application of Homology Modeling; A Molecular Visualization Method

Piyusha Sharma1*, Anjana Thakur2 and Neha Kumari2
1
Assistant Professor, Department of Life Sciences,
Desh Bhagat University, Mandi Gobindgarh, 147301 (Punjab), India.
2
Research Scholar, Department of Biotechnology,
Shoolini Institute of Life Science and Business Management (Himachal Pradesh), India.
(Corresponding author: Piyusha Sharma*)
(Received 27 April 2022; Accepted 24 June 2022)
(Published by Research Trend, Website: www.researchtrend.net)
ABSTRACT: Diverse Research in areas like protein engineering, human genetics, structure-based drug
design and analysis of protein function knowledge of the three-dimensional structure of proteins is a
prerequisite. It is ultimately dictated by protein sequence and is typically necessary to comprehend the
mechanism of protein function. It takes a lot of time and doesn't always work with all proteins, particularly
membrane proteins, to determine the structure of a protein using experimental techniques like X-ray
crystallography or NMR spectroscopy. Protein modelling aims to predict a three-dimensional structure
from its sequence with an accuracy using a technique called homology modelling also known as
comparison modelling or knowledge-based modelling. The current review offers a methodical evaluation of
the efficacy of frequently employed (and commercially accessible) homology modelling software for
therapeutically important proteins, evaluating both the sequence alignments and the created 3D models.
The ab-initio approach and homology modelling can be grouped into two extreme categories for theoretical
structure prediction. One objective of the first method is to predict folds using physical chemistry concepts.
A protein sequence's three-dimensional structure can be predicted using a second method, which
principally bases its prediction on the protein sequence's similarity to other proteins with known
structures.
Keywords: Homology modeling, X-ray crystallography, NMR spectroscopy, databases, 3D structure.

I. INTRODUCTION challenging, will encourage the development of a

variety of new computational techniques that can close
A precise definition of homology is having a shared
the knowledge gap and advance our understanding of
evolutionary ancestor. As a result, homology cannot be
the relationship between protein structure and function.
partial and is a qualitative representation of the nature
Homology modelling has been made easier and more
of the relationship between two or more objects. There
efficient by fully automated workflows and servers,
is either an evolutionary connection or there isn't.
which also enable users without specialised
Normally, a homology claim must remain a hypothesis.
computational knowledge to create accurate protein
Sequence or three-dimensional similarities, the
models and have simple access to modelling outcomes,
relationships between which may be quantitatively
their display, and interpretation [34]. The description
defined, are examples of supporting data indicating a
and inclusion of software created for protein modelling
homologous relationship. The fact that the three-
are part of the current review.
dimensional structures of a group of proteins that are
thought to be homologous are more conserved than II. REVIEW OF LITERATURE
their fundamental structures is a key finding in
The idea behind homology modelling is that
homology modelling. By using homologues with
homologous proteins' 3D structures are more conserved
extremely little sequence similarity, this observation
than their sequences [35]. The pioneering homology
has been exploited to create models of proteins. An
modelling articles were published in the late 1970s [8].
effort is made to create homologous protein models of
Finding an appropriate template is the first step in the
an unknown. The ability to accurately predict protein
procedure; Insertions, deletions, and substitutions of
structure, which was not even possible a few years ago,
residues are made after an alignment is created [30].
has been made possible by recent advances in
Homology modeling is applied for constructing protein
homology modelling, particularly in the detection of
3D structures exploiting its primary sequence available
distant homologues, alignment of sequences with
in databases and utilizing prior knowledge gained from
template structures, modelling of loops and side chains,
structural similarities with other proteins [11]. Studying
and error detection. The ongoing efforts to solve protein
the underlying theory and implementation techniques of
structures, which can be time-consuming and frequently
the database's structure, storage, design, maintenance
Sharma et al., International Journal of Theoretical & Applied Sciences, 14(2): 61-67(2022) 61
provides the ease in processing and analysis of the data Protein Structure Prediction (CASP) experiments is to
contained within the database [37]. By using online establish benchmarking criteria for the protein structure
computing resources, high-resolution protein 3D prediction techniques used by various internet servers
structures can be created for research. The modeller and applications. They keep track of advancements in
should be able to access and use the atomic coordinates the field of modelling protein structure from sequence.
for creating homology models through the accessible These experiments' primary goals are to ensure the
experimental 3D-structure sources [10]. models' overall quality, predictability, and evaluation of
Software for homology modelling. There are the parameters offered by various tools [39]. A service
numerous tools and servers for homology modelling for comparative modelling that predicts protein
that are designed to create a whole model using query structure is called Homer (Homology ModellER). It
sequences. In order to create constraints on atomic creates a model structure using a single template
distances, dihedral angles, and other parameters, structure and an alignment in FASTA format (PDB
MODELLER employs the query structures. These format). The CaspR web server is based on a set of
constraints are then paired with statistical distributions common software applications that are popular among
obtained from several homologous structure pairings in protein crystallography and bioinformatics researchers.
the PDB. Sequences and structures are combined by The T-COFFEE software is the first step in the
Modeller 0 to provide a complete alignment that may procedure to create a trustworthy multiple alignment.
be manually modified and inspected with molecular The provision of a dependability index [CORE index]
graphics software. By wrapping the software tool for each place in the alignment is a distinctive feature of
MODELLER in a graphical user interface, Accelrys T-COFFEE. Better multiple alignments are produced
Software Inc.'s programme for modelling protein by T-COFFEE, which integrates structure and
homology is known as DSModeler [25]. Given a sequencing data, and MODELLER's homology models
template(s) and a sequence alignment, DSModeler benefit as a result [4]. An automated service for
creates protein homology models. A molecular force modelling comparative protein structures is called
field, a database of crystal structures in the PDB, and ModWeb. It accepts one or more sequences in the
distance constraints determined from the template are FASTA format and generates models for them using the
used to forecast the structures. Disulfide bonds and cis- best Protein Data Bank template structures. A free
prolines are examples of restrictions and ligand online homology modelling server is Phyre2 Protein
structures that can be introduced into the model Homology/analogy Recognition Engine 2. To represent
building stage. A technique that incorporates those portions of the proteins in question that have no
knowledge-based potentials from well-known crystal discernible similarity to recognised structures, Phyre2
structures generates loops from scratch. Software called uses a new ab-initio folding simulation termed Poing
PROFIT was created using protein fold recognition [22]. In order to satisfy spatial constraints (dihedral and
(threading) technology by Proceryon Biosciences [27]. distances), FASPR is a very helpful tool for protein
Sequence alignments are generated utilizing potential in structure modelling and protein design due to its
terms for atom pair and protein-solvent interactions that excellent accuracy, speed, and determinacy for
are based on information. To generate an alignment of modelling the side-chains of both native and non-native
the target sequence with a template structure, these main-chain conformations [12]. Geno3D models
potentials are used with dynamic programming and comparative protein structures. Homology or
frozen approximation. Optimized gap penalties, gap comparative protein structure modelling is where
restrictions, and potentials are all employed to evaluate Geno3D is most frequently employed. Geno3d accepts
how well the alignment would be [5]. The ExPASy input in a manner similar to FASTA, but all that is
Web server provides access to SWISS-MODEL, a fully required is a single letter of the code. The output is in
automated system for protein structure homology PDB format, which may be viewed in any molecular
modelling. In 1993, Manuel Peitsch launched SWISS- modelling programme. SPORulate server provides
MODEL. A sequence alignment and a PDB file for the several tools, including SWISS-MODEL, CPH models,
template are provided as input. The knowledge-based and SDSC1, are made available through this server to
homology model is created using the ProModII tool assist the user in submitting the sequence for homology
after these are transmitted via a server [23]. Complete modelling. For secondary structure prediction and Fold
backbone and side chain building, loop creation, and identification, it also contains a number of programmes.
model quality assurance, including packing, are all A technology called Wloop the loop homology
components of model construction [29]. In order to modelling server is used to forecast the backbone
create a composite template, PrISM does homology structures of protein loops based on their sequences and
modelling utilising alignment, choosing each secondary flank backbone structures [19].
structure from the best suitable template. Loop Modeled structures through homology modeling.
modelling is done using ab- initio techniques, and side- Over the years, many homology models have been
chain dihedrals are either obtained from the template or developed. Antibodies and other proteins important in
predicted based on the structure's main chain torsion human biology and medicine have been used as targets.
angles using a neural network approach [36]. For Nearly 50% of all drug development programmes target
constructing homology models, COMPOSER makes GPCRs since they are the largest family of signalling
use of a variety of template structures. The primary goal receptors in cells [33]. To evaluate the accuracy of
of the biannual Critical Assessment Approaches for structural predictions and the relevance of those
Sharma et al., International Journal of Theoretical & Applied Sciences, 14(2): 61-67(2022) 62
predictions to chemotaxis research, homology models and STARD3 from humans to worms/insects. Using the
of the chemotaxis proteins CheW from E. coli and T. ConSurf web server, the scores were projected onto a
maritima were built. The sequence for modelling E. coli STAR homology model's three-dimensional structure.
CheW was found in the UniProt database (Entry ID: The potential cholesterol recognition/interaction amino
P0A964), and it was modelled using the T. maritime acid consensus (CRAC) domain and steroid binding
CheW structure as a model that was found in the pocket were shown in relation to the inner
Protein Data Bank (PDB ID: 1K0S) [2]. Using the mitochondrial membrane using the three-dimensional
programme MODELLER9v4, the structure of SRCR1 structure of human CYP11A1 [6]. Osmium basilicum, a
(residues 95-203 on DMBT1, renumbered as 1-109 in plant that has been studied using homology modelling,
this article) was developed based on the knowledge of has many medicinal uses, including decreasing blood
the structure of M2bp SRCR domain (PDB ID: 1BY2) pressure, acting as an antispasmodic, and cleansing
[3]. The homologous X-ray crystal structure of the blood. Homology modelling was used to establish the
Hepatitis C viral helicase served as a basis for creating protein's 3D structure. To locate the most appropriate
the 3D model of the Classical Swine Fever virus templates for homology modelling, a BLAST P search
(CSFV) helicase. The model's geometry, fold against the Protein Data Bank (PDB) was conducted
recognition, and compliance with the standards using default parameters. The homology model was
necessary as a member of the Flaviviridae virus family predicted using Protein Structure Prediction Server
were successfully assessed in silico [31]. Exo-inulinase (PS)2 based on software MODELLER [13]. From the
from Penicillium sp. TN-88(BAC16218) and endo- Protein Knowledgebase of UniProt
inulinase from Penicillium sp. TN-88(BAA19132) (http://www.uniprot.org), the amino acid sequence of
structural modelling and active site research are human MK5 (Swiss-Prot: Q8IW41) was obtained.
reported. For structural modelling, the exo-inulinase BLAST via UniProt was used to find close homologues
sequence from Penicillium sp. TN-88(BAC16218) was having accessible crystal structures in the Protein
obtained from NCBI (http://www.ncbi.nlm.nih.gov/) Databank (http://www.pdb.org) [16].The three-
and uploaded to Swiss model dimensional structure of MP was created using
(http://swissmodel.expasy.org). The RCSB Protein Data homology modelling and molecular dynamic (MD)
Bank was used to model the structures of the obtained methods (Marine alkaline protease). The MP target
sequences (PDB)[26]. A novel strategy based on sequence (accession number ACY25898) was retrieved
additional data from the template structures has been from the protein database of the National Center for
developed to address the shortcomings of standard Biotechnology Information (NCBI). On the BLAST
homology modelling. The strategy uses the space filled web service (http://blast.ncbi.nlm.nih.gov), a sequence
by ligands or substrates in the template structures to similarity search for this protease was conducted
prevent the target protein from folding [32]. In addition against sequences from the Protein Data Bank (PDB)
to being necessary for healthy T-cell development, the database. MODELLER (version 9.9), a programme
BCL11B transcription factor has recently been linked to used for homology modelling of protein three-
the pathogenesis of T-cell acute lymphoblastic dimensional structures, was used to construct MP's
leukaemia (T-ALL), which is brought on by TLX over tertiary structure. The predicted structures were stored
expression or Atm deficiency. Based on the high- in PDB format and organised by scores derived from
resolution crystal structure of Egr1 (Zif268) in GA341 and discrete optimised protein energy (DOPE)
association with DNA, structural homology modelling scoring. The PROCHECK tool
was utilised to simulate BCL11B tandem ZF2-ZF3 zinc (https://saves.mbi.ucla.edu/) is used to analyse the
finger binding to a common GC-rich DNA energy and stereochemical properties of the modelled
oligonucleotide sequence. Using SWISS-MODEL to protein structures from the Structural Analysis and
calculate the structural model, a high-quality structure Verification of Protein (SAVES) website. The
with a model-template C-root mean square deviation of PROCHECK tool is also used to create a
2.9 Angstroms was produced [9]. Using comparative Ramachandran plot for each target in order to determine
modelling, a structural model of mature L. mexicana whether the residues were located in an energetically
CPB2.8 CTE was created in order to get the protein's advantageous area. With the use of SWISS-PDB
3D structure for covalent docking investigations and Viewer, energy minimization and loop creation for
subsite residue identification. When compared to its residues in the Ramachandran plot's forbidden zones
template structure, the final homology model of were carried out. Cancer cells' survival and
CPB2.8 CTE had a C RMSD score of 0.699. By antiapoptotic mechanisms are crucially activated by the
superimposing the two protein structures, the homology phosphatidylinositol 3-kinase/AKT signalling pathway.
model was then structurally compared to bovine A total of 22 putative PH domain inhibitors were found
cathepsin B (BtCatB, PDB ID 1QDQ).By using the using specialised docking software. Using UNITY
coordinates of the human MLN64 protein (1EM2) from (Tripos, L.P.), a three-dimensional pharmacophore
the Brookhaven Protein Database (BPD), an automated search was conducted based on the hydrogen-bonding
comparative protein modelling server (Swiss-Model) at pattern between the ligand, inositol (1,3,4,5)-
the University of Geneva was able to create the three- tetrakisphosphate, and the PH domain of AKT (1H10)
dimensional structure of STAR proteins (cytosolic [21]. The cystic fibrosis transmembrane conductance
steroidogenic acute regulatory protein). ClustalW was regulator protein (CFTR), which causes the disease,
used to align a total of 13 sequences, including STAR was modelled using homology theory (CF). Using
Sharma et al., International Journal of Theoretical & Applied Sciences, 14(2): 61-67(2022) 63
MODELLER, a homology model of the open-channel conserved in all known members of the forisomes
state of CFTR (without the R-domain) was created [24]. proteins. Using the Protein Homology/analogY
For bubaline Pregnancy associated glycoprotein 2, the Recognition Engine (PHYRE) web service, the
first 3D structure and potential activities have been structural prediction was carried out. The thioredoxin-
proposed using homology modelling and comparative fold containing protein [Structural Classification of
genomics methods. Then, in order to create the 3D Proteins (SCOP) code d1o73a_], a member of the
model of buPAG2, the query sequence and template Glutathione peroxidase family, was chosen as a
structure were supplied as inputs in MODELLER9v10 template for modelling the spatial structure of Ps.SEO1
[7]. Actin-binding proteins called filamins help to based on investigations of local sequence alignment.
organise the actin-based cytoskeleton in cells. Human Comparison of the primary sequence, better match
filamin was modelled using homology modelling with quality, and alignment precision were used to make the
Modeller 9v5. The final model's reliability was decision. Motif 1 (EVF) is conserved in Ps.SEO1,
demonstrated through Verify 3D and PROCHECK Viciafaba (Vf.For1), and Medicagotruncatula
evaluations. Human filamin isoforms A, B, and C's (MT.SEO3); motif 2 (KKED), which is present in all
FASTA sequences were downloaded from Uniprot. The forisome proteins, is also conserved; and motif 3, which
FASTA tool was used to query this sequence against is present in Ps.SEO1 and Vf.For1. All known
the PDB. Given a protein sequence (target), forisomes proteins were shown in the alignment studies
comparative modelling predicts the 3-D structure of the to have conserved amino acids (shown by asterisks) and
filamin A, B, and C isoforms based mostly on the conservative amino acid modifications (marked by
alignment to the template (structure determined dots) along the modelled amino acid stretch [28].
experimentally) [14].A human stomach lipase (PDB ID: Target sequences for homology modelling included the
1HLG) was used as a template to generate the HIV2 (UniProt entry P04584), SIVagm (UniProt entry
Arabidopsis thaliana lipase homology model (NP Q02836), and SIVmac (UniProt entry P05897) capsid
179126). The stereochemical quality and side chain protein sequences. As structural models, the
environment of this model was then evaluated [15]. To experimental crystal structures of HIV1 (PDB ID
study the interaction between ligands and substrates, 1AFV), N-MLV (PDB ID 1U7K), and B-MLV (PDB
natural substrates such as tributyrin, trioctanoin, and ID 3BP9) were employed. The MUSCLE algorithm
triolen were docked into the model. Swiss-PDB Viewer was used to accomplish multiple sequence alignment
4.0.1 was used to create the homology model. This between the target and template sequences. The
programme has a user-friendly interface that enables sequence similarity between the capsid proteins of HIV
simultaneous analysis of many proteins. Using the and SIV, which are both members of the lentivirus
relevant software, the stereochemical and amino acid retroviral genus, ranges from 60 to 86%. The N-MLV
environment quality of the Arabidopsis thaliana lipase and B-MLV capsid proteins share 97% of their
homology model was validated. The pathophysiology sequence among themselves, and MLV is a member of
of illness involves the enzyme coagulase significantly. the gammaretroviral genus. Only about 13% of the
The crystal structure of the Staphylococcus aureus capsid protein sequences of lenti viruses and
coagulase is yet unknown. In order to create a three- gammaretro viruses are identical. The MODELLER
dimensional model of the coagulase in S. aureus, programme Version 9 was used to build model
homology modelling is being used in the research. The structures of the HIV-2, SIVagm, and SIVmac capsid
NCBI database provided the coagulase sequence from proteins based on target-template sequence alignments.
S. aureus (Accession Number: CAC 84776.1). The 1. For each protein, 2000 models were created, and the
Protein Data Bank database was queried using the final model was chosen based on the modeler's intended
query sequence from S. aureus coagulase to determine function. The UCSF Chimera program's MatchMaker
the corresponding protein structure that could be command was used to carry out the structural sequence
utilised as a template (or templates) by the BLAST tool. alignments. This alignment is based on a combination
On the basis of the alignment of the target and template of secondary structure correspondence and residue
sequences of coagulase, the 3D homology models were identity/similarity. While the latter is calculated using
constructed using the crystal structure coordinates of the Kabsch and Sander algorithm, the former is derived
the templates. Discovery Studio by Accelerys carried using the Needleman-Wunsch algorithm and the
out the procedures (San Diego, CA, USA). BLOSUM-62 residue similarity matrix [18]. The
Understanding coagulase's native conformation and the coupling of homology modelling and chemical cross-
mechanism of coagulase action requires an linking mass spectrometry provides the side-view
understanding of the three-dimensional structure of the crossover configuration, provides two basal cylinders
enzyme [20]. For the Pisum sativum sieve element view consolidating the crucial functions of the
occlusion 1 (Ps.SEO1) (forisomes) protein, a anchoring domains made up of the ApcE PB loop and
homology-based three-dimensional model was created. ApcD which is necessary for regulating photochemical
The 3D structure of Ps.SEO1 was modelled using a activity [17].
region of amino acids (residues 320 to 456) that is well

Sharma et al., International Journal of Theoretical & Applied Sciences, 14(2): 61-67(2022) 64
III. CONCLUSION functionalities (protein engineering). In the creation of
drugs, it is frequently employed. Based on a survey of
The most comprehensive method for predicting a
the literature, we have created Table 1, which includes
protein's three-dimensional structure from its amino
a list of the applications and programmes used in
acid sequence is homology modelling. This technique
homology modelling. This table lists software
creates realistic 3D models. We observed that
programmes along with a description of the programme
homology modelling is significant because it discovers
and a link to its website. For automatic protein
linkages between sequence patterns and structural
modelling, tools like Geno3d, Swiss Model, CHP
characteristics and further illustrates how proteins have
models, and Homology are employed. For loop
developed. It creates assumptions regarding a protein's
modelling, Wloop is employed. Programming is used in
function, forecasts how a sequence will fold, and builds
conjunction with Profit, CaSpR, and Phyre 2. The basic
a model by comparison with an existing structure with a
goal of homology modelling is to accurately anticipate
comparable sequence. It aids in the study of how
a structure from its sequence, matching the results of
mutations affect structure, functions and forecasts the
experiments.
impact of a novel mutation on either. Additionally, it
creates completely new proteins with inventive
Table 1: Tools for Homology Modeling (Comparative Modeling).
Sr. No. Program Website address Program description
Automatic modeling of protein three-
1. Geno3d http://pbil.ibcp.fr/
dimensional structure
An automated knowledge-based protein
2. Swiss Model http://www.expasy.org/swissmod/SWISS-MODEL.html modeling server; first approach and
optimize
Automated neural-network based protein
3. CPHmodels Http://www.cbs.dtu.dk/services/CPHmodels/
modeling server
A program for automated protein Homology
4. Modeller http://salilab.org/
Modeling
Similar package as CHARMm. Developed
5. Amber http://amber.scripps.edu/
by Kollaman's group at UCSF
Automatic Homology Modeling module.
6. Homology http://www.accelrys.com/ The software suite also has Modeller,
SeqFold modules,
7. Wloop http://psb00.snv.jussieu.fr/wloop/ The Loop Homology Modeling Server
V.Friend's What-IF Homology Modeling
8. What-If Server http://www.cmbi.kun.nl/gv/servers/WIWWWI/
Server
Send jobs by 'SPORulation' (meta server) to
http://cgat.ukm.my/spores/Predictory/sporulate/s_predict_metaser
9. SPORulate selected servers available above using the
ver.html
respective server's default values.
Alignment of hidden Markov models via
10. Phyre2 www.sbg.bio.ic.ac.uk/phyre2/html
HHsearch
Used in combination with dynamic
11. PROFIT http://www.proceryon.com/
programming
Templates are used to provide an average
12. COMPOSER www.tripos.com/data/SYBYL/composer 072505.pdf
frame work form building the structure
13. CASP http://predictioncenter.org Ensure overall quality of the modles
Set of non-redundant chains extracted from
14. ModWeb http://salilab.org/modweb
structure in the PDB
Used with the protein crystallography and
15. CaspR http://igs-server.cnrs-mrs.fr/Caspr/index.cgi
bioinformatics communities

Docking is often utilised to provide a more thorough physiologically active molecules during the crucial
explanation of knowledge that has already been early conceptual stage of a drug discovery project. One
discovered through experimental research. However, of the advantages of this approach is the design of
the docking tool can be used more broadly as a way to molecules that are specifically targeted at particular
describe the shape and interfacial characteristics of a therapeutic target proteins. Such selective substances
protein without attempting to relate the results to can even be used to learn more about the physiological
experimental data. Docking is not flawless, but we function of brand-new medication targets. Being in its
demonstrate here that variations in its level of infancy, in silico protein structure-based prediction of
repeatability can be instructive in and of themselves. metabolism and toxicity of small compounds,
Here are few examples of homology modelling being particularly CYP inhibition and induction and hERG
successfully used in drug development. Homology inhibition, may only be able to classify. The homology
models have aided in the formulation of a number of modelling technique offers one way to fill the gap until
effective pharmacological drugs in the lack of comprehensive experimental structures of proteins that
experimental structures for drug target proteins. The are significant from a pharmacological standpoint are
ease and speed with which homology models can be available. The integration of AI has played a significant
constructed is one of their benefits. Additionally, these role in the development of homology modeling
models could provide evidence in favour of medicinal accuracy. It is evident that the accuracy of results
chemists' assumptions about how to produce obtained through the homology models can be
Sharma et al., International Journal of Theoretical & Applied Sciences, 14(2): 61-67(2022) 65
improved by adding new developed modules. The [10]. Haddad, Y., Adam, V., and Heger, Z. (2020). Ten
improved version of modeling tools will enhance the quick tips for homology modeling of high-resolution
efficiency of homology modeling. Protein homology protein 3D structures. PLoS computational
detection based on sequence has become one of the biology, 16(4): e1007449.
most sensitive and exact methods for predicting protein [11]. Hameduh, T., Haddad, Y., Adam, V. and Heger,
structure. Despite the progress, weakly similar proteins Z. (2020). Homology modeling in the time of collective
with different evolutionary histories still make and artificial intelligence. Computational and
homology identification highly difficult [1]. Structural Biotechnology Journal, 18: 3494-3506.
[12]. Huang, X., Pearce, R., and Zhang, Y. (2020).
ACKNOWLEDGEMENT
FASPR: an open-source tool for fast and accurate
I extend my sincere thanks to Dr. Geeta Puri, Director protein side-chain packing. Bioinformatics, 36(12):
SILB, Dr. Shalini Sharma, HOD Dept of Biotechnology 3758-3765.
and Dr. Deepinderpal Singh for giving me proper [13]. Idrees, S., Nadeen, S., Kanwal, S., Eshsan, B.,
guidance throughout the course of study. I acknowledge Yousaf, A., Nadeen, S. and Rajoka, M.I. (2011).In
the hard work of Research scholars Ms. Neha and silico sequence analysis, homology modeling and
Ms.Anjana. function annotation of Ocimumbasilicum hypothetical
protein GICT28_OCIBA. International Journal
REFERENCES
Bioautomation, 16(2): 111-118.
[1]. Bhattacharya, S., Roche, R., Shuvo, M. H. and [14]. Kumar, S. (2011). Homology modeling and
Bhattacharya, D. (2021). Recent advances in protein consensus protein disorder prediction of human filamin.
homology detection propelled by inter-residue Bioinformation 6(10): 366-369.
interaction map threading. Frontiers in Molecular [15]. Laskowski, R. A., Jabłońska, J., Pravda, L.,
Biosciences, 8: 643752. Vařeková, R. S. and Thornton, J. M. (2018). PDBsum:
[2]. Cashman, D.J., Ortega, D.R., Zhulin, I.B. and Structural summaries of PDB entries. Protein
Bautry, J. (2013). Homology modeling of CheW science, 27(1): 129-134.
coupling protein of the chemotaxis signaling complex. [16]. Lindin, I., Wuxiuer, Y., Kufareva, I., Abagyan,
Public library of Sciences, 8(8): e70705. R., Moens, U., Sylte, I. and Ravna, A.W. (2013).
[3]. Chu, Y., Li, J., Wu, X., Hua, Z. and Wu, Z. (2013). Homology modeling and ligand docking of mitogen-
Identification of human immunodeficiency virus type 1 activated protein kinase-activated proteins kinase
(HIV-1) gp 120 binding sites on scavenger receptor 5MK5. Theoretical Biology and Medical
cysteine rich 1 (SCR) domain of gp 340. Journal of Modelling, 10(1): 1-21.
Biomedical Science, 20(1): 44. [17]. Liu, H., Zhang, M. M., Weisz, D. A., Cheng, M.,
[4]. Claude, J.B., Suhre, K., Notredama, C., Claverie, Pakrasi, H. B. and Blankenship, R. E. (2021). Structure
J.M. and Abergel, C. (2013). CaspR: a web server for of cyanobacterialphycobilisome core revealed by
automated molecular replacement using homology structural modeling and chemical cross-linking. Science
modeling. Oxford Journals, (32): 606-609. advances, 7(2): eaba5743.
[5]. Domingues, F.S., Koppensteiner, W.A., Jaritz, M., [18]. Maillard, P.V., Zoete, V., Michielin, O. and
Prlic, A., Weichenberger, C., Wiederstein, M., Trono, D. (2011). Homology – based identification of
Floeckner, H., Lackner, P. and Sippl, M.J. (1999). Capsid determination that protect HIV 1 from human
Sustained performance of knowledge-based potentials TRIM5ά restriction. Journal of Biological Chemistry,
in fold recognition. Proteins Supplements, (3): 112– 286(10): 8128-8140.
120. [19]. Mifsud, D. and Bateman, A. (2002). Membrane-
[6]. Fan, J. and Papodopoulos, V. (2013). Evolutionary bound progesterone receptors contain a cytochrome b5
origin of the mitochondrial cholesterol transport like ligand-binding domain. Genome Biology, 3(12):
machinery reveals a universal mechanism of steroid 0068.1-0068.5.
hormone biosynthesis in animals. Pubic Library of [20]. Mohamed, N.A. and Mohamad, R. (2012).
Science One, 8(10): e76701. Homology modeling of coagulase in Staphylococcus
[7]. Ganguly, B. and Prasad, S. (2012). Homology aureus. Bioinformation, 8(9): 412-414.
modeling and functional annotation of bubaline [21]. Moses, S.A., Ali, M.A., Zuohe, S., Guny , L.D.,
pregnancy associated glycoprotein. Journal of Animal Zhou, L.L., Lemos, R., Ihle, N., Mash, E.A., Powis, G.
Science Biotechnology, 3(1): 13. and Meuillet, E.J. (2009). In vitro and in vivo activity
[8]. Greer, J. (1980). Model for haptoglobin heavy of novel small molecule inhibitors targeting the
chain based upon structural homology. Proceeding of pleckstrin homology domain of protein kinase B/AKT.
the National Academic Science USA, 77(6): 3393-3397. Cancer Research, 69(12): 5073-5081.
[9]. Gutierrez, A., Kentsis, A., Sanda, T., Holmfeldt, L., [22]. Nema, V. and Pal, S.K. (2013). Exploration of
Chen, S.C., Zhang, J., Protopopov, A., Chin, L., freely available web-interface for comparative
Dhalberg, S.E., Neuberg, D.S., Silverman, L.B., homology modeling of microbial protein.
Winter, S.S., Hunger, S.P., Sallan, S.E. and Zha, S. Bioinformatics, 9 (15): 796-801.
(2011). The BCL11B tumor soppresor is mutated across [23]. Peitsch, M.C. (1995). ProMod: Automated
the major molecular subtypes of T-cell acute knowledge-based protein modeling tool PDB Quarterly
lymphoblastic leukemia. Blood, the Journal of the Newsletter, 72: 4
American Society of Hematology, 118(15): 4169-4173. [24]. Rahman, K.S., Cui, G., Harvey, S.C. and
McCarty, N.A. (2013). Modeling the conformational
Sharma et al., International Journal of Theoretical & Applied Sciences, 14(2): 61-67(2022) 66
changes underlying channel opening in CFTR. Public dengue (Type II)virus. Computational and
Library of Science One, 8(9): e74574. mathematical methods in medicine 2013.
[25]. Sali, A. and Blundell, T.L. (1993). Computational [32]. Vlachakis, D., Kossida, S. (2013). Molecular
protein modeling by satisfaction of spatial restraints. modeling and pharmacophore elucidation study of the
Journal of Molecular Biology, (234): 779-815. classic swine fever virus helicase as a promising
[26]. Singh, P.K. and Shukla, P. (2012). Molecular pharmacological target. Peer J, (1): e85.
modeling and docking microbial inulinase towards [33]. Vyas, V.K., Ukawala, R.D., Ghaye, M., and
perceptine enzyme- substrate interactions. Indian Chintha, C. (2012). Homology Modeling a Fast Tool
Journal of Microbiology, 52(3): 373-380. for Drug Discovery: Current perspective. Indian
[27]. Sippl, M.J. and Weitckus, S. (1992). Detection of Journal of Pharmaceutical Science, 74(1): 1-7.
native-like models for amino acid sequences of [34]. Waterhouse, A., Bertoni, M., Bienert, S., Studer,
unknown three-dimensional structure in a data base of G., Tauriello, G., Gumienny, R. and Schwede, T.
known protein conformations Proteins: Structure, (2018). SWISS-MODEL: homology modelling of
Function, and Bioinformatics, 13(3): 258-271. protein structures and complexes. Nucleic acids
[28]. Tuteja, N. and Umate, P. (2010). Conserved research, 46(1): 296-303.
thioredoxin fold is present in Pisum sativum L. sieve [35]. Wieman, H., Tondel, K., Anderssen, E., and
element occlusion -1 protein. Plant signal Behavior, Drablos, F. (2004). Homology modeling of targets for
5(6): 623-628. drug design. Mini – Reviews in Medicinal Chemistry,
[29]. Van Gunsteren, W., Billeter, S.R., Eising, A.A., (4): 793-804.
Hünenberger, P.H., Krüger, P., Mark, A.E., Scott [36]. Yang, A.S., and Honig, B. (1999). Sequence to
W.R.P. and Tironi, IG (1996). Biomolecular structure alignment in comparative modeling using
simulation: the GROMOS96 manual and user PrISM. Proteins: Structure, Function, and
guide. Vdf Hochschulverlag AG an der ETH Zürich, Bioinformatics, 37(S3): 66-72.
Zürich, 86: 1-1044. [37]. Yang, J., Li, Y., Liu, Q., Li, L., Feng, A., Wang,
[30]. Venselaar, H., Jooster, R.P., Vroling, B., T. and Lyu, J. (2020). Brief introduction of medical
Baakman, C.A.B., Hekkelman, M.L., Krieger, E. and database and data mining technology in big data
Vriend, G. (2010). Homology modeling and era. Journal of Evidence‐Based Medicine, 13(1): 57-69.
spectroscopy , a never ending love story. European [38]. Zemla, A., Venclovas, Moult J. and Fidelis, K.
Biophysics Journal, 39(4): 551-563. (2001). Processing and evaluation of predictions in
[31]. Vlachakis, D., Kontopoulos, D.G. and Kossida, S. CASP4. Proteins: Structure, Function, and
(2013). Space constrained homology modeling: The Bioinformatics, 45(S5): 13-21.
paradigm of the RNA- dependent RNA polymerase of

Sharma et al., International Journal of Theoretical & Applied Sciences, 14(2): 61-67(2022) 67