HOMOLOGY MODELING

Nixon MendezDepartment of Bioinformatics

• 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

• 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?

• 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

Steps Overview

• 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

• 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

• COMPOSERhttp://www.tripos.com/sciTech/inSilicoDisc/bioInformatics/matchmaker.html

• MODELER http://salilab.org/modeler

• InsightII http://www.msi.com/

• SYBYL http://www.tripos.com/

Comparative Modeling Server & Program

SCOPE

• 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)

• Opportunity: Postdoctoral Fellow (#211314) @ Henry M. Jackson Foundation for theAdvancement of Military Medicine -- Bethesda, MD (US) posted on Monday, April 04, 2016

• Opportunity: Bioinformatics Specialist -- Genomics @ Fred Hutchinson Cancer ResearchCenter -- Seattle, WA (US) posted on Thursday, March 31, 2016

• Opportunity: Senior Bioinformatics Engineer -- Python, genomics, cancer @ Dana-FarberCancer 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 GenomicMedicine -- San Diego, CA (US) posted on Wednesday, March 16, 2016

Job opportunity & Post Doctoral

• 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

THANK YOU