homology modeling

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Homology Modeling. Seminar produced by Hanka Venselaar. Homology modeling. Yes we can. % identity. *. # residues. * Actually, modelling is possible here, but we cannot get an alignment…. NSDSECPLSHDG || || | || NSYPGCPSSYDG. NSDSECPLSHDG. ?. - PowerPoint PPT Presentation

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  • Homology ModelingSeminar produced by Hanka Venselaar

  • Homology modeling # residues% identity** Actually, modelling is possible here, but we cannot get an alignmentYes we can

  • Homology modeling in shortPrediction of structure based upon a highly similar structure

    Add sidechains, Molecular Dynamics simulation on modelKnown structureCopy backbone and conserved residuesModel!

  • The 8 steps of Homology modeling

  • 1: Template recognition and initial alignment

  • 1: Template recognition and initial alignment

    BLAST your sequence against PDB

    Best hit normally template

  • 1: Template recognition and initial alignment

  • 2: Alignment correction

    Functional residues conservedUse multiple sequence alignmentsDeletions shift gaps

    Both are possibleMultipe sequence alignment Sequence with known structureYour sequence

  • 2: Alignment correction

    Core residues conservedUse multiple sequence alignmentsDeletions in your sequence shift gaps

    Known structure FDICRLPGSAEAV Model FNVCRMP---EAI Model FNVCR---MPEAI Correct alignmentF-D--A-V

  • 1: Template recognition and initial alignment2: Alignment correction

  • 3: Backbone generation

    Making the model.Copy backbone of template to modelMake deletions as discussed(Keep conserved residues)

  • 1: Template recognition and initial alignment2: Alignment correction3: Backbone generation

  • 4: Loop modeling

    Known structure GVCMYIEA---LDKYACNC Your sequence GECFMVKDLSNPSRYLCKCLoop library, try different options

  • 1: Template recognition and initial alignment2: Alignment correction3: Backbone generation4: Loop modeling

  • 5: Side-chain modeling

    Several optionsLibraries of preferred rotamers based upon backbone conformation

  • 1: Template recognition and initial alignment2: Alignment correction3: Backbone generation4: Loop modeling5: Sidechain modeling

  • 6: Model optimizationMolecular dynamics simulationRemove big errors

    Structure moves to lowest energy conformation*

    *Which has nothing to do with the real coordinates...

  • 1: Template recognition and initial alignment2: Alignment correction3: Backbone generation4: Loop modeling5: Sidechain modeling6: Model optimization7: Model validation

  • 7: Model ValidationSecond opinion by PDBreport /WHAT IFErrors in active site? new alignment/ template

    No errors? Model!

  • 1: Template recognition and initial alignment2: Alignment correction3: Backbone generation4: Loop modeling5: Sidechain modeling6: Model optimization7: Model validation8: Iteration8: Iteration8: Iteration8: Iteration

  • Model!1: Template recognition and initial alignment2: Alignment correction3: Backbone generation4: Loop modeling5: Sidechain modeling6: Model optimization7: Model validation8: Iteration8: Iteration8: Iteration8: Iteration

  • 8 steps of homology modeling1: Template recognition and initial alignment2: Alignment correction3: Backbone generation4: Loop modeling5: Side-chain modeling6: Model optimization7: Model validation8: Iteration

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