structural bioinformatics - homology modeling & its scope
TRANSCRIPT
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