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

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

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

5. Macromolecular Interaction Scenario
Separation
Function
Diffusion
Interaction

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

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

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

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

10. Planar Case

18. R3 Case
1BRS

19. Delaunay Triangulation

20. Delaunay Triangulation

21. Pockets
[EFL98]

41. Retraction

42. Retraction

43. 2-Manifold with Boundary

45. 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

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

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

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

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

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

51. Summary Current Status Uniqueness
Definition of a surface of interaction between proteins
Construction of a hierarchy of interfaces
Apparent localization of the important regions in protein-protein interactions
Uniqueness
Bridges biology, geometry, and topology

52. Goals Hot-spot Prediction Theoretical Mutagenesis
Computational Kinetics
Interface Classification

53. Acknowledgements Duke Biochemistry Duke Computer Science
Johannes Rudolph
Duke Computer Science
Herbert Edelsbrunner
Pankaj Agarwal
Sergei Bespamyatnikh (UT Dallas)
Alper Üngör
Yusu Wang