1. Development of on-line database & tool for protein interface analysis Suk-hoon Jung

2. Page  2 Contents  Introduction  What have done  What to do  Discussion

3. Page  3 Introduction  Interface : binding site of domain-domain or protein-protein interaction  Extracted from 3D structure in PDB d1 : HHRDSASDFEWETDVPMGQHNFQASDFSDFVV d2 : HHWEFNMAGEISNDOFKENSLEOFMTLRTSDFK d3 : ADSFADNGKIPMFEERFERWFSDFSDFTLRTLRTT d4 : HASDFASSDSTTDVPMSDFAADSFEERFELRTSDF 3D protein structures in PDB DDI Interfaces

4. Page  4 Introduction  Analysis of protein interface give an insight into Protein-protein interaction Pathway formation Dynamic protein-protein interaction network  Currently, public database offers only domain-domain interface data extracted from 3D structure in PDB  Need tools and database for protein interface analysis

5. Page  5 PPI interface prediction  DDI interface can be extended to PPI that is not recorded in PDB, by domain-protein mapping  d2 in p1 interacts with d3 but not with d1 in p2, since the interface for d1 is occupied by intra-molecular interaction. PPI p1{d1, d2, d4} p2{d1, d3} d1 d2 d3 d1 d4 d1 d2 d3 3D structure Predicted PPI docking p1 p2

6. Page  6 Mutually Exclusive Interactions (MEI)  In static Protein interaction network (PPIN), A pair of PPIs may mutually exclusive when they bind to overlapping surface of a protein  MEI cannot be activated together simultaneously  Simultaneous Protein Interaction Network (SPIN) –a snapshot of dynamic PPIN based on MEI P2 P1 P3 Common interfacial surface on P1 P1 P3 P2 P1 P3 OR a) PPIN b) spin 1 b) spin 2

7. Page  7 Interface detection issue  A domain has mutations, insertions, and deletions according to the protein which it appears in.  MEI detection calculates indexes in the all cases of PDB entity with buffer residues –Is not accurate –Cannot identify interface template –Cannot specify PPI docking interface PDB1: -------------------------------------------- PDB2: --------------------------------------- PDB3: ---------------------------------------------------- PDB4: ----------------------------------------------

8. Page  8 Interface clustering  Sequence clustering identifies interface template  SCOPPI provide clustered interfaces  Using clustered interfaces –Accuracy of MEI detection will increase –Can Specify PPI docking interface PDB1: ------------------------- ---- ----- - - - ------- PDB2: ------ ------ - --------------- ------ ----- PDB3: -------------------------------------------------- PDB4: -------------------- ------ -- ---------- -- ----- Interface 1 Interface 2 Interface 3

9. Page  9 MEI detection issue  A pair of domains may interact in several ways mediated by different interfaces  Those cases should be formulated  Current research regards it as ‘No’, but it may lose some correct cases –Without interface clustering, we cannot specify distinct interfaces when the their indexes are overlapped d1 d2 d3 Are they mutually exclusive? -if Yes : loose MEI, 9244 DDI MEIs -if No : strict MEI, 3505 DDI MEIs

10. Page  10 Proposed database provides  Data –Protein-Protein interface candidates Representation of DDI in Protein & PPI pair –Mutually Exclusive Interactions & their evidences in PDB 13456052 evidences for D-D MEIs from 6524 DDIs in PDB  Function –Protein-Protein interface prediction –SPIN generation –Path routing in PPIN d1 d2 d3 d1 d4 p1 p2

11. Page  11 Discussion  Proposed database contains what I have done for SPIN based protein complex prediction  For the further research dealing with MEI, MEI data should be refined and organized –Dynamic representation of PPIN –Functional analysis of hub-protein : date-hub vs. party hub –Routing rule for Signaling pathway prediction Date-hub Party-hub SPIN PaPa PbPb MEI