FlexTree%20Package

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Overview

• Background
• FlexTree package
• Development
• Application of FlexTree
• Summary

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Docking Study

• Lock and Key model
• Induced Fit
• 50 of dockings fail because of induced-fit

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Background

• Biological Molecules
• Large conformational space
• Docking Study
• docking related conformational sub-space is
  relatively small
• still too large to explore explicitly

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Example
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FlexTree Basic Objects

• Tree
• Node
• Shape
• Motion
• Shape-Motion Convolution
• Shape Combiner

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XML

• lt?xmlversion"1.0"?gt
• ltroot
• file"1hvrLigRotated.pdbqs"
• name"1hvr"
• id"99"
• selectionString"1hvrLigRotated"
• convolve"FTConvolveApplyMatrix"gt
• ltnode
• name"chainA"
• id"1"
• selectionString"1hvrLigRotatedA"
• convolve"FTConvolveApplyMatrixToCoords"gt
• ltnode
• name"CoreA"
• id"2"
• selectionString"1hvrLigRotatedA,PRO1-GLU34,
  
• motion"FTMotion_Generic
• motionParams"matrixListlist float 0.995
  0.078
• shape"FTLines

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Programming

• Python
• PMV (Python Molecule Viewer)
• Vision (Previously know as ViPEr )
• SciPy (Genetic Algorithm package)
• C
• Scoring function
• Computational intensive

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Application of FlexTreeSearching the
conformational sub-space
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FlexTree-based ComputationsAutomated Docking
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Genetic Algorithm
Float hinge angle
Hinge
Genome
The motion parameters are used as Genes
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Docking Test Result

• Population size 500, converges after 91
  generations
• the best docked conformation
• interaction energy -21.35 Kcal/mol
• compare with experimental result -20.7 Kcal/mol
• RMSD 0.35 Å (all atoms ) v.s. crystal
  structure

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FlexTree Summary

• Represents the flexibility hierarchically
• Given knowledge of protein flexibility
• Conformational sub-space
• Tree structure
• Real-time 3D Visualization
• Python C
• Conformation search Docking test
• http//www.scripps.edu/sanner/python

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Acknowledgment

• Dr.Michel Sanner
• Dr.Daniel Stoffler
• The Molecular Graphics Lab _at_ TSRI
• SciPy community
• NBCR National Biomedical Computational Resources
• NIH Grant BISTI,R21/R33GM65609