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A Definition of Interfaces for Protein Oligomers

A Definition of Interfaces for Protein Oligomers. Andrew Ban Biochemistry & Computer Science Duke University. Protein-Protein Complexes. Ribonuclease Regulation. Venom Neutralization. Retrovirus Propogation. Cell Signaling. Oxygen Transport. Protein-Protein Complexes. DNA Upkeep.

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A Definition of Interfaces for Protein Oligomers

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  1. A Definition of Interfaces for Protein Oligomers Andrew Ban Biochemistry & Computer Science Duke University

  2. Protein-Protein Complexes Ribonuclease Regulation Venom Neutralization Retrovirus Propogation Cell Signaling Oxygen Transport

  3. Protein-Protein Complexes DNA Upkeep Amino Acid Synthesis Nitrogen Metabolism Assisted Protein Folding

  4. Macromolecular Interaction Scenario Separation Function Diffusion Interaction

  5. Methods of Attack • Experimental • Binding Assays • Mutagenesis • Computational • Molecular Simulation • Docking • Interface Characterization

  6. Current Knowledge • Basic statistics • Geometric complementarity • Hot-spot theory • Electrostatic steering

  7. Interface Characterization • Current paradigm • Two components • “Coarse” definitions • Reproducibility issues • Characterization needs • General definition of the “Interface” • Localization of important regions

  8. Intuition • Best separation is a “medial surface” between proteins • Interesting regions should be protected in some manner

  9. Planar Case

  10. R3 Case 1BRS

  11. Delaunay Triangulation

  12. Delaunay Triangulation

  13. Pockets [EFL98]

  14. Retraction

  15. Retraction

  16. 2-Manifold with Boundary

  17. Further Retraction • Extension of the “seal” intuition • Dome structure • Identification by topological persistence pairing [ELZ99] • Relative Persistence • Compare sizes of mouth vs. sink • Gives a hierarchy of interfaces

  18. Level-of-Focus Hierarchy 725,690 394,490 70.183 32.475 10.207 1BRS Interface: Seal Threshold (infinity to –infinity)

  19. Level-of-Focus Hierarchy 3.5121 1.8840 1.0287 .70203 -infinity 1BRS Interface: Seal Threshold (infinity to –infinity)

  20. Persistent = Important? 1A22 Interface: Hot Spots

  21. Future Work • Geometric and topological measures • Energy measures • Critical points • Simultaneous critical points • Extension to volumes • Skin surface

  22. Energy Maps 1BRS Interface: Isolines of Power Distance

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