1. Computational prediction of protein-protein interactions Rong Liu 2014-04-22

2. Quaternary structure

3. Types of protein-protein interactions Homo-oligomers vs. hetero-oligomers Permanent vs. transient interactions Strong transient Weak transient Covalent vs. non-covalent interactions Classification based on function enzyme-inhibitor antibody-antigen Others (e.g. hormone-receptor, signaling-effector)

4. Experimental methods to detect PPI Yeast two hybrid (Y2H) Tandem affinity purification coupled to mass spectrometry (TAP-MS) Co-inmunoprecipitation (CoIP) Protein microarrays Phage display Surface plasmon resonance ……

6. Reliability of high-throughput methods

7. PPI database

8. A sample of DIP protein table

9. List of interacting partners

10. Graphic representation of interactions Nodes are proteins Edges are PPIs The center node is DIP:1143N Edge width encodes the number of independent experiments identifying the interactions. Green (red) is used to draw core (unverified) interactions. Click on each node (edge) to know more about the protein (interaction).

12. Techniques to study the protein complex structures X-ray crystallography Nuclear magnetic resonance spectroscopy Electron Microscopy

13. Header of PDB file

14. Format of PDB file

16. Preparation of PPI and non-PPI datasets PPI dataset (Gold standard dataset) Data from multiple database At least two separate publications Each of these publications needs to have a binary evidence code Non-PPI dataset Random selection from all possible protein pairs Proteins come from different sub-localization

17. The first non-PPI database

18. PPI prediction based on homology

19. InParanoid8

20. Genome context-based methods

21. Domain association-based method

22. Domain combination

23. Machine learning-based method

24. Feature representation of amino acid sequences

26. Protein feature server

27. Validation of the predicted PPIs

28. Protein-protein binding interface

29. Hotspots in binding interface (ΔΔG >2kcal/mol)

30. Definition of binding interface Define surface residue (DSSP, NACCESS) Define interface residue Distance-based method Solvent accessible surface area-based method

31. Format of DSSP file

32. Characteristics analysis of binding interface

33. Features of transient and obligate interactions

34. Features used to predict PPI binding interface Sequence conservation Propensity of residue types in binding regions Secondary structure Solvent accessibility Protrusion index Side-chain conformational entropy

35. Position specific scoring matrix and neighborhood

36. Training and testing Cross-validation and independent test Balanced positive and negative samples Evaluation measures

37. State-of-the-arts of feature-based prediction

38. Similarity between binding interfaces

39. Protein interface conservation across structure space

40. Performance comparison between different algorithms

41. Hybrid method

42. Residue interaction network

43. Network-based features Degree centrality Closeness centrality Betweenness centrality Clustering coefficient

44. Protein complexes and small-world networks

45. Network-based features of other binding sites

46. Graph-based interface alignment

47. InterPreTS: protein Interaction Prediction through Tertiary Structure

48. Structure-based prediction of protein–protein interactions on a genome-wide scale

49. Protein Docking

50. Procedure of protein docking

51. Search of conformations

52. Scoring function

53. Docking programs and benchmark

54. Evaluation measures

55. Structure visualization tools FeatureRasMolCn3DPyMolSWISS- PDBViewer Chimera ArchitectureStand-AlonePlug-inStand-AloneWeb-enabled Manipulation Power LowHigh Hardware Requirements Low/ModerateHigh ModerateHigh Ease of UseHigh; command line Moderate HighModerate;GUI +command line Special FeaturesSmall Size; easy install Powerful GUI GUI; ray tracing Powerful GUIGUI; collaboration Output QualityModerateVery highHigh Very high DocumentationGood LimitedGoodVery good SupportOnline; Users groups SpeedHighModerate Moderate/Slow OpenGL SupportYes

56. Pymol http://www.jhu.edu/pfleming/bioinform/files/PyMOL_Tutorial.pdf http://wenku.baidu.com/view/483b70fa0242a8956bece41f.html

57. Application of PPI network