Session ii g2 overview protein modeling mmc

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  • First, I will explain some keywords in PHM and give you an introduction about what PHM is. Protein is an important and essential nutrient for everyone.All kinds of proteins in biological body is made up of….
  • In introduction we said that Homology Modeling build the model from amino acid sequence and experimental 3D structure. The experimental 3D structure we said there is the template.
  • Basically in this tool, your input is sequence, then the tool will search the database to find the best template. sometimes several templates are produced for a single query sequence, but we only choose the most likely candidate.
  • You can see it compares target and template sequence.This target template alignment are used to generate the 3D model of protein.
  • After we talk about model construction, Next part I am going to talk about is model chosen. PMP provides access to various server for model building, and quality assessment. I use PSI to get and collect pdb files for input sequence.
  • This figure is what protein model portal uses for structure modeling. We can see steps with blue stars are homology modeling steps what we are using.Besides it, the portal provides more like structure prediction when no template found. Or visualization of a model after built it etc.
  • After we submit the sequence and wait about one or two hours, the result will sent to you by email. Depends on different server, sometime they just send you pdb files, or sometimes they send you a link to a page contains model and some validation.Here we take Swiss Model as an example. In Model summary page we can see template selection stuff, like xxxx. And also some model quality parameter, xxxx.The model it produce we can download as many different format like, xxxx.
  • This table shows the result I get from protein model portal. I got 8 models from one input sequence from these 5 server
  • There are lots of server existing for model building. The input sequence using different server will creates many pdb files.We need to choose the best model from them, but HOW?
  • To decide which model is best we need test the pdb file on validation tools. There are lots of tools but here I just list three here. They are xxxx,All those parameters have different meaning. Basically, we need to understand what value is a good, what value is bad for each tool. To choose the best model, we need to test many validation tools and compare the quality parameters.
  • Session ii g2 overview protein modeling mmc

    1. 1. Protein HomologyModeling
    2. 2. Introduction• What is protein?- providing energy- building/repairing tissue in body• Amino Acids- protein is made up of amino acids.- 20 standard amino acids
    3. 3. Introduction• Sequence- string represent the primary structure of theproteinPrimary structure3D structure
    4. 4. Introduction• Homology Modeling refers to constructing anmodel of the "target" protein from its amino acidsequence and/or an experimental 3D structure (the"template")?
    5. 5. Introduction• Homology Modelingo When we want to know the 3D structure of a protein(target) thathas not been solvedo You have only the sequenceo If there exist a solved experimental 3D structure(template) issimilar to target proteino We can use software to arrange the backbone of the sequence.
    6. 6. Model ProductionStep 1 - Template SelectionStep 2 - Target-Template AlignmentStep 3 - Model ConstructionStep 4 - Model Validation
    7. 7. Step 1. Template Selection• First step in homology modeling is the identificationof the best template structure.• The simplest method of template identification relieson database search techniques such as BLAST.
    8. 8. Step 1. Template Selection• BLAST(Basic Local Alignment Search Tool)Input: sequenceOutput: templates with Identities, E-value …
    9. 9. Step 2. Target-TemplateAlignment• Comparison between target & template.• Used to generate the model of protein.
    10. 10. Step 3. Model Construction• Fragment assemblyrelied on the assembly of a complete model fromclosely related solved structures.• Segment matchingdivides the target into short segments, matched toits own template fitted from the Protein Data Bank.• Spatial restraint basedcommon software used is MODELLER.
    11. 11. Step 4. Model Validation• An example:Tool: Errat
    12. 12. Model SelectionThe Protein Model Portal• ModWeb• M4T• Swiss Model• I-TASSER• HHpred
    13. 13. PMP Work Flowzz
    14. 14. Swiss Model
    15. 15. Model SelectionServer Pdb files Model NameHhpred 1 (Chun)HHpredI-TASSER 3 (Chun)I-TASSER model1 C-score=1.13(Chun)I-TASSER model2 C-score=-1.39(Chun)I-TASSER model3 C-score=0.70M4T 1 (Chun)M4TModelWeb 2 (Chun)ModelWeb Model_fd(Chun)ModelWeb Model_f5Swiss Model 1 (Chun)SwissModel
    16. 16. Model SelectionSequenceDifferentServerpdb1pdb2pdb3pdb4pdb5……bestpdb ?
    17. 17. Model SelectionModel Name Errat(overallquality factor)Verify 3D( percentage ofthe residues had anaveraged 3D-1D score >0.2)Prove(Z score)(Chun)HHpred 86.856 93.52% 0.349(Chun)I-TASSER model1 45.153 93.52% -0.075(Chun)I-TASSER model2 48.329 77.31% 0.042(Chun)I-TASSER model3 52.806 87.78% -0.176(Chun)M4T 77.041 92.52% -0.137(Chun)ModelWeb Model_fd 77.836 96.12% 0.050(Chun)ModelWeb Model_f5 76.350 91.46% 1.196(Chun)SwissModel 85.492 93.42% 0.302
    18. 18. Conclusion• Homology modelingo Input sequence -> Template -> Build Model -> Validation• Need understand and use tools well• It cost time to validate model
    19. 19. Questions?

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