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A Definition of Interfaces for Protein Oligomers
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Transcript of A Definition of Interfaces for Protein Oligomers
ITR Meeting 2002
A Definition of Interfaces for Protein Oligomers
Andrew Ban
Biochemistry & Computer Science
Duke University
ITR Meeting 2002Yih-En Andrew Ban
Protein-Protein Complexes
Cell Signaling
Retrovirus Propogation Venom Neutralization
Oxygen Transport
Ribonuclease Regulation
ITR Meeting 2002Yih-En Andrew Ban
Protein-Protein Complexes
Amino Acid Synthesis Assisted Protein FoldingNitrogen Metabolism
DNA Upkeep
ITR Meeting 2002Yih-En Andrew Ban
Macromolecular Interaction Scenario
Separation
Diffusion
Function
Interaction
ITR Meeting 2002Yih-En Andrew Ban
Methods of Attack
• Experimental Binding Assays Mutagenesis
• Computational Molecular Simulation Docking Interface
Characterization
ITR Meeting 2002Yih-En Andrew Ban
Current Knowledge
• Basic statistics• Geometric
complementarity• Hot-spot theory• Electrostatic steering
ITR Meeting 2002Yih-En Andrew Ban
Interface Characterization
• Current paradigm Two components “Coarse” definitions Reproducibility issues
• Characterization needs General definition of the
“Interface” Localization of important
regions
ITR Meeting 2002Yih-En Andrew Ban
Intuition
• Best separation is a “medial surface” between proteins
• Interesting regions should be protected in some manner
ITR Meeting 2002Yih-En Andrew Ban
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
su
susf
),(
ITR Meeting 2002Yih-En Andrew Ban
Level-of-Focus Hierarchy
725,690 394,490 70.183 32.475 10.207
1BRS Interface: Seal Threshold (infinity to –infinity)
ITR Meeting 2002Yih-En Andrew Ban
Level-of-Focus Hierarchy
3.5121 1.8840 1.0287 .70203 -infinity
1BRS Interface: Seal Threshold (infinity to –infinity)
ITR Meeting 2002Yih-En Andrew Ban
Future Work
• Geometric and topological measures
• Energy measures Critical points Simultaneous critical points
• Extension to volumes Skin surface
ITR Meeting 2002Yih-En Andrew Ban
Summary
• Current Status 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
ITR Meeting 2002Yih-En Andrew Ban
Goals
• Hot-spot Prediction• Theoretical Mutagenesis• Computational Kinetics• Interface Classification