Post on 03-Jan-2016
Computational prediction of protein-protein interactions
Rong Liu2014-04-22
Quaternary structure
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)
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• ……
Reliability of high-throughput methods
PPI database
A sample of DIP protein table
List of interacting partners
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).
Techniques to study the protein complex structures
• X-ray crystallography• Nuclear magnetic resonance spectroscopy• Electron Microscopy
Header of PDB file
Format of PDB file
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
The first non-PPI database
PPI prediction based on homology
InParanoid8
Genome context-based methods
Domain association-based method
Domain combination
Machine learning-based method
Feature representation of amino acid sequences
Feature representation of amino acid sequences
Protein feature server
Validation of the predicted PPIs
Protein-protein binding interface
Hotspots in binding interface (ΔΔG >2kcal/mol)
Definition of binding interface • Define surface residue (DSSP, NACCESS)
• Define interface residue• Distance-based method• Solvent accessible surface area-based method
Format of DSSP file
Characteristics analysis of binding interface
Features of transient and obligate interactions
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
Position specific scoring matrix and neighborhood
Training and testing
• Cross-validation and independent test• Balanced positive and negative samples• Evaluation measures
State-of-the-arts of feature-based prediction
Similarity between binding interfaces
Protein interface conservation across structure space
Performance comparison between different algorithms
Hybrid method
Residue interaction network
Network-based features
• Degree centrality
• Closeness centrality
• Betweenness centrality
• Clustering coefficient
Protein complexes and small-world networks
Network-based features of other binding sites
Graph-based interface alignment
InterPreTS: protein Interaction Prediction throughTertiary Structure
Structure-based prediction of protein–proteininteractions on a genome-wide scale
Protein Docking
Procedure of protein docking
Search of conformations
Scoring function
Docking programs and benchmark
Evaluation measures
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Structure visualization toolsFeature RasMol Cn3D PyMol SWISS-
PDBViewerChimera
Architecture Stand-Alone Plug-in Stand-Alone Web-enabled Web-enabled
Manipulation Power
Low High High High High
Hardware Requirements
Low/Moderate High High Moderate High
Ease of Use High; command line
Moderate Moderate High Moderate;GUI +command line
Special Features Small Size; easy install
Powerful GUI
GUI; ray tracing
Powerful GUI GUI; collaboration
Output Quality Moderate Very high High High Very high
Documentation Good Good Limited Good Very good
Support Online; Users groups
Online; Users groups
Online; Users groups
Online; Users groups
Online; Users groups
Speed High Moderate Moderate Moderate Moderate/Slow
OpenGL Support Yes Yes Yes Yes Yes
Pymol
• http://www.jhu.edu/pfleming/bioinform/files/PyMOL_Tutorial.pdf• http://wenku.baidu.com/view/483b70fa0242a8956bece41f.html
Application of PPI network