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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.
1. Complete
protein
2. Binding
site
Input
SiteEngine
Output
1. 3D transformation.
2. Similarity
Score
Biological Motivation
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
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Potential ligands and ligand fragments.
Prediction of side effects.
Inferring a function of a novel protein.
Biological classifications.
3-D Database Searches
Application I:
Application II:
Application III:
Query: a binding site
Query: a binding site
DB: complete proteins
DB: binding sites
Query: a complete
protein
DB: binding sites
DB of complete
proteins
DB of binding sites
Representation
I. Each amino acid is
represented by a set of its
physico-chemical
properties (Schmitt 02’).
II. Each property
creates a physicochemical patch on
the protein surface.
- Hydrogen bond acceptor
- Hydrogen bond donor
- donor/acceptor
- Hydrophobic Aliphatic
- Aromatic (PI) contacts
III. The solid angle shape
function (Connolly 83’) is
calculated at the center of
each physico-chemical
patch.
Recognition of adenine binding sites
A 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.
- cAMP-dependent protein
kinase (1atp)
*The ligands are displayed for verification only!
- MJ0577 Structural genomics
protein (1mjh, ranked 7)
Searching the Entire PDB
1. Searching the ASTRAL dataset with the adenine binding site of c-AMP
dependent protein kinase (1atp).
Replication factor C (1iqp, purple).
Ranked 19.
2. Searching the ASTRAL dataset with the estradiol binding site of sex
hormone-binding globulin (1lhu).
D-Ala-D-Ala ligase (1iow). Ranked 31.
Tropinone reductase (2ae2).
Ranked 43.
Estrogen sulfotransferase (1aqu).
Ranked 38.
Web Server
http://bioinfo3d.cs.tau.ac.il/SiteEngine