1 / 53

A Definition of Interfaces for Protein Oligomers

This work by Andrew Ban explores the definition and characterization of interfaces in protein oligomers, highlighting essential interactions within protein-protein complexes. Discussing topics such as regulatory mechanisms in ribonuclease activity, venom neutralization, and retrovirus propagation, the study employs various methods including experimental binding assays, mutagenesis, molecular simulations, and docking. Additionally, it addresses current knowledge on interface properties, geometric complementarity, and the importance of hot-spot theory. The implications for protein dynamics and metabolism are also analyzed.

sebastian-mathis
Download Presentation

A Definition of Interfaces for Protein Oligomers

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  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

More Related