Functional Sites Structural Search Engine [ About SiteEngine][ Server Help][ Download]
Recognizes regions on the surface of one protein that resemble a specific binding site of another.

Below is a detailed description of the main forms used in the SiteEngine server.
To speed up the search please click on the stage on interest.

Forms and stages of the SiteEngine server:
Stage1 - Input molecules definition
Stage2 - Selection of the chain and the binding site of interest
Stage3 - Process of SiteEngine
Stage4 - Output of SiteEngine


Stage1 - Input molecules definition:
The first stage in activating the SiteEngine is the definition of the molecules of interest. The definition is performed through the form below.
The first field specifies the molecules that will be searched for the binding site of interest. The second field specifies the molecule from which the binding site will be extracted. If the molecules are available in the Protein Data Bank (PDB) the PDB codes are to be specified, otherwise the molecules of interest can be uploaded to our server. Using the PDB codes speeds up the process, since no file transfer is required.

form1

Stage2 - Selection of the chain and the binding site of interest:
First, the user can specify the specific chains of interest that are to be searched in the complete molecule. This restriction will significantly speed up the search process.
Second the user must specify the ligand that is present in the binding site of interest. The region of radius 4.0A  around the ligand will be extracted and used as the searched pattern. SiteEngine will recognize regions, similar to this pattern, on the surface of the complete molecule.
Below is an example of a molecule (pdb:1a27) that has two ligands EST and NAP. By selecting the ligand of interest the user specifies the regions of interest that his is interested to search in the other molecule

form2

Stage3 - Process of SiteEngine:
This window shows the process of activation of SiteEngine. The five main stages are presented and those that are complete are checked in the checkbox.
In most of the cases the most time consuming stages are the construction of the surfaces.

form3

Stage4 - Output of SiteEngine:
This window presents the output of the SiteEngine algorithm. The 10 top ranking solutions are presented. These represent the 10 regions of the surface of the complete molecule that are recognized to be most similar to the binding site of interest. The file aligned.pdb is the superimposition of the two molecules by the transformation recognized by SiteEngine. It can be either downloaded of viewed directly from the browser. The file contains the superimposition of the two molecules as well as the functional groups that are recognized to be shared by the regions. These are also detailed in the output table. To view these features in the rasmol view please use the following rasmol script.
The output table of SiteEngine presents the details of the common functional groups.
Below is the description of the columns of the table (click on the column of interest to jump to a description):
Chain.ID
AminoAcid
Property
Source
Dist
Conserved AA
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Chain.ID:
The protein chain, followed by the identity of the amino acid
AminoAcid:
The one letter amino acid code. However it must be noted that the method is based on the physico-chemical properties and does not consider the identity of the amino acids. These are only displayed for the convenience of analysis.
Property:
The physico-chemical property that is matched by the algorithm. The method is based on a representation of each amino acid of a protein as a set of features that are important for its interaction with other molecules. The abbreviations of these features are:
DON - Hydrogen bond donor
ACC - Hydrogen bond acceptor
DAC - Hydrogen bond donor and acceptor (e.g in histidine)
ALI - Aliphatic Hydrophobic property
PII - Aromatic property (pi contacts)
Source:
This field specifies whether the matched property is contributed by the backbone or the side-chain of the amino acid.
The abbreviations are:
b - feature contributed by the backbone
s - feature contributed by the backbone
Dist:
The  distance in space measured between the matched features.
Conserved AA:
Marks the features shared by the two molecules that are contributed by residues with the same identity of the amino acid.

Reference: Shulman-Peleg A, Nussinov R, Wolfson HJ, Recognition of functional sites in protein structures. J Mol Biol. 2004 Jun 4;339(3):607-33.

Contact: shulmana@tau.ac.il