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SiteEngine: Functional Sites Structural Search Engine
Shulman-Peleg A., Nussinov R. and Wolfson H. J. Recognition of Functional Sites in Proteins Structures, J. Mol. Biol. 339(3), 607 633.
SiteEngine• Recognizes surface regions of one protein
that resemble a specific binding site of another.
• Measures the similarity of physico-chemical and geometrical properties.
SiteEngineInput Output
1. Complete protein
2. Binding site
1. 3D transfor-mation.
2. Similarity Score
Biological Motivation
Potential ligands and ligand fragments. Prediction of side effects. Inferring a function of a novel protein. Biological classifications.
3-D Database Searches
DB of binding sites
DB of complete proteins
Application I:
Query: a binding site
DB: complete proteins
Application II:
Query: a binding site
DB: binding sites
Application III:
Query: a complete proteinDB: binding sites
Representation
I. Each amino acid is represented by a set of its physico-chemical properties (Schmitt 02’).
II. Each property creates a physico-chemical patch on the protein surface.
III. The solid angle shape function (Connolly 83’) is calculated at the center of each physico-chemical patch.
- Hydrogen bond acceptor- Hydrogen bond donor- donor/acceptor- Hydrophobic Aliphatic- Aromatic (PI) contacts
- cAMP-dependent protein kinase (1atp)
- MJ0577 Structural genomics protein (1mjh, ranked 7)
*The ligands are displayed for verification only!
Recognition of adenine binding sitesA benchmark data set (121 proteins) was searched for binding sites similar to that of cAMP-dependent protein kinase (1atp).
Ranked 7 was the an ATP binding site of a structurally different “hypothetical” protein MJ0577 from Methanococcus jannaschii.
Searching the Entire PDB
Replication factor C (1iqp, purple). Ranked 19.D-Ala-D-Ala ligase (1iow). Ranked 31.
1. Searching the ASTRAL dataset with the adenine binding site of c-AMP dependent protein kinase (1atp).
2. Searching the ASTRAL dataset with the estradiol binding site of sex hormone-binding globulin (1lhu).
Estrogen sulfotransferase (1aqu). Ranked 38.
Tropinone reductase (2ae2). Ranked 43.
