Structural and Physico-Chemical Alignment of Protein-Protein Interfaces [About I2I-SiteEngine][Server Help]
Interface-to-Interface (I2I)-SiteEngine compares pairs of interacting protein binding sites.

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 I2I-SiteEngine server:
Stage1 - Input complexes definition
Stage2 - Selection of the interacting chains that determine the interface of interest
Stage3 - Process of I2I-SiteEngine
Stage4 - Output of I2I-SiteEngine


Stage1 - Input molecules definition:
The first stage in activating the I2I-SiteEngine is the definition of the complexes of interest. The definition is performed through the form below.
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 - Interface definition The method automatically extracts all pairs of interacting protein chains and prompts the user to select the chains of interest. Each pair of the presented interacting protein chains (separated by a semicolon) define a potential protein-protein interface. I2I-SiteEngine will compare only the interfaces defined by the selected chains.
Single chain protein molecules that have no protein binding partner in the submitted PDB file can not be compared by the I2I-SiteEngine method


form2

Stage3 - Process of I2I-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 I2I-SiteEngine:
This window presents the output of the SiteEngine algorithm. The correspondence between the chains of the two interfaces is a-priori unknown, e.g. given two interfaces determined by chains Z:I and E:I respectively, we have to determined whether the binding site of chain Z in one interface is more similar to that of chain E or chain I in the other. I2I-SiteEngine checks both options and selects the highest ranking correspondence. The output of I2I-SiteEngine is the list of the matching functional groups of the corresponding binding sites that constitute the interfaces. Suppose that in the example above we have recognized that the correct correspondence is to align the binding site chain Z in one interface to chain E in the other. Then the output of I2I-SiteEngine will first present the "Match List of Side 1", i.e. the functional groups common to the aligned binding sites of chains E and Z. The it will present the "Match List of Side 2", which will contains the matching functional groups recognized in the binding site of chains I in both interfaces.

The 10 top ranking solutions are presented. These represent the highest scoring ways of superimposition of the interfaces of interest. The file aligned.pdb is the superimposition of the two complexes by the transformation recognized by I2I-SiteEngine. It can be either downloaded of viewed directly from the browser. The file contains the superimposition of the two complexes 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.

Contact: shulmana@tau.ac.il

Reference: Shulman-Peleg A, Mintz S,Nussinov R, Wolfson HJ,  J Mol Biol. 2004 Jun 4;339(3):607-33. Protein-Protein Interfaces: Recognition of Similar Spatial and Chemical Organizations,  Accepted to WABI-4th Workshop on Algorithms in Bioinformatics, LNCS, Norway, Sep. 14-17 [PDF].