Homology modeling also known as comparative modeling uses homologous sequences with known 3D structures for the modelling and prediction of the structure of a target sequence Homology modeling is one of the most best performing prediction methods that gives “accurate” predicted models.

1. HOMOLOGY MODELING
Nixon Mendez
Department of Bioinformatics

2. • Proteins of similar sequences fold into similar
structures and perform similar biological
functions.
• The protein sequence has the intrinsic
information to encode the protein structure.
Sequence-Structure-Function
Relationships

3. • Homology modeling also known as comparative
modeling uses homologous sequences with known 3D
structures for the modelling and prediction of the
structure of a target sequence
• Homology modeling is one of the most best
performing prediction methods that gives “accurate”
predicted models.
What is Homology Modeling?

4. • Retrieving the sequence to be modeled (target sequence)
• Identifying suitable templates from PDB using BLAST
• Go for the best hit (> 30 - 40% identity)
• No need to do modeling if hit is 100% identical to target
• Aligning target sequence with template sequences
• Remove gapped positions
• Remove residues in target that are missing in template
• Final alignment should be in PIR format
• Performing homology modeling using MODELLER
• Change the aligned PIR file to add additional information required by
MODELLER
• Mind the syntax (most errors occur because of not following the syntax)
• Model quality check – WHATIF, PROCHECK, VERIFY3D, ERRAT
• Quantitative comparison of model with experimental structure
• Assess RMSD using SUPERPOSE
Homology modelling practical steps,
in brief

5. Steps Overview

6. • To model proteins with lower similarities( eg < 30% sequence
identity)
• To increase accuracy of models and to make it fully automated
• Improvements may include simulataneous optimization techniques
in side chain modeling and loop modeling
• Although comparative modelling needs significant improvement, it
is already a mature technique that can be used to address many
practical problems
Challenges

7. • SWISS Model : http://www.expasy.org/swissmod/SWISS-MODEL.html
• WHAT IF : http://www.cmbi.kun.nl/swift/servers/
• The CPHModels Server : http://www.cbs.dtu.dk/services/CPHmodels/
• 3D Jigsaw : http://www.bmm.icnet.uk/~3djigsaw/
• SDSC1 : http://cl.sdsc.edu/hm.html
• EsyPred3D : http://www.fundp.ac.be/urbm/bioinfo/esypred/
Automated Web-Based Homology Modelling

8. • COMPOSER
http://www.tripos.com/sciTech/inSilicoDisc/bioInformatics/matchmaker.ht
ml
• MODELER http://salilab.org/modeler
• InsightII http://www.msi.com/
• SYBYL http://www.tripos.com/
Comparative Modeling Server & Program

9. SCOPE

10. • In Dr. Khaled Barakat’s Lab, Faculty Of Pharmacy,
University Of Alberta, Immediate Phd opening and
another one in September 2016. Term - 4 year
PhD programmes
Baylor College of Medicine PhD - Structural and
Computational Biology and
Molecular Biophysics, MD/PhD
Graduate School of Biomedical
Sciences
Boston University PhD-Bioinformatics, MS Department of Bioinformatics
Indiana University at
Bloomington
MS bioinformatics, PhD School of informatics, Department of
Biology
Keck Graduate Institute of
Applied Life Sciences
Professional Masters of
Bioscience, PhD Computational
and Systems Biology
PhD: KGI and
the Claremont Graduate
University Degrees Department(s)

11. • Opportunity: Postdoctoral Fellow (#211314) @ Henry M. Jackson Foundation for the
Advancement of Military Medicine -- Bethesda, MD (US) posted on Monday, April 04, 2016
• Opportunity: Bioinformatics Specialist -- Genomics @ Fred Hutchinson Cancer Research
Center -- Seattle, WA (US) posted on Thursday, March 31, 2016
• Opportunity: Senior Bioinformatics Engineer -- Python, genomics, cancer @ Dana-Farber
Cancer Institute -- Boston, MA (US) posted on Thursday, March 31, 2016
• Opportunity: Postdoctoral Research Fellow in computational and synthetic biology @
University of Edinburgh, UK posted on Monday, March 28, 2016
• Opportunity: Senior Biostatistician, Interdisciplinary Health Sciences Initiative @
University of Illinois at Urbana/Champaign posted on Monday, March 28, 2016
• Opportunity: Postdoctoral Fellow @ Rady Children's Hospital-Institute for Genomic
Medicine -- San Diego, CA (US) posted on Wednesday, March 16, 2016
Job opportunity & Post Doctoral

12. • Illustrating and homology modeling the proteins of the Zika virus
• Structural characterization of human CRTh2: a combined homology
modeling, molecular docking and 3D-QSAR-based in silico approach
•
• Homology modeling and docking studies of ENPP4: a BCG activated
tumoricidal macrophage protein
• Homology modeling, docking, and molecular dynamics simulation of
the receptor GALR2 and its interactions with galanin and a positive
allosteric modulator
• Optimized method for TAG protein homology modeling: In silico and
experimental structural characterization
Current Research- 2016

13. THANK YOU