MultiBind: Multiple Alignment of Protein Binding Sites


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Multiple Alignment of Protein Binding Sites Recognizes Spatial Chemical Binding Patterns Common to a Set of Protein Structures

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

Forms and stages of the MultiBind server:
Stage1 - Input PDB files definition
Stage1 - Input binding sites definition
Stage3 - Running MultiBind
Stage4 - Output of MultiBind
Stage5 - Jmol options

Stage1 - Input PDB files definition:
The first stage in activating MultiBind is the definition of the complexes and binding sites 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 in a single ZIP file.

form1

Stage2 - Input binding sites definition:

Currently, MultiBind defines a binding site by the surface area around the ligand of interest (Connolly points within the distance of 4A of the ligand). The form below prompts the user to select the ligand of interest that will define the binding site.
form2

Note: Unbound protein molecules that have no small molecule binding partners (defined as HETATM records in PDB files) can not be compared by the current version of MultiBind web server.

Stage 3 - Process of MultiBind:
This window shows the process of activation of MultiBind. 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

Note: The user does not have to wait for the process to finish, since he/she will receive an email with the link to the output.
Stage 4 - Output of MultiBind:
The window below presents the output of the MultiBind algorithm. Each pair of rows details the interacting pseudocenters (physico-chemical properties) of two PPI chains. Each three columns present the details of a specific PPI: (i) chain identifier and residue number; (ii) residue type; (iii) pseudocenter type, which can be donor (DON), acceptor (ACC), mixed donor/acceptor (DAC), hydrophobic aliphatic (ALI) or aromatic (PI). The next column presents the origin of the feature: backbone(b) or side-chain(s) if it is the same for all the matched pseudocenters. The last column details whether all the pseudocenters were initiated by amino acids with the same identity.

The 5 top ranking solutions are presented. Each solution can be viewed with Jmol by clicking on the "View solution with Jmol". In addition the PDB file with the superimposition of all the complexes can be downloaded as a separated file (aligned.pdb).
The details of the following column fields can be found below (click 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.
Stage 5 - Jmol options:
Each solution can be visualized with Jmol. The default view presents the superimposition of all the complexes, with their corresponding ligands and the matched physico-chemical properties. The molecules are colored by model (according to the order of input molecules, the first is cyan, the second is magenta, the third is yellow). The physico-chemical properties (pseudocenters) are represented as balls. Hydrogen bond donors are blue, acceptors - red, donors/acceptors - green, hydrophobic aliphatic - orange and aromatic - gray. The surface points that have a similar location in all the molecules are represented as smaller dots with the same coloring.
form5

The "Radio groups" at the bottom allow to hide the protein molecules and focus on the physico-chemical properties, the ligands or the amino acids.
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Please don't hesitate to contact if you have further problems or questions: shulmana@tau.ac.il

Reference: Shatsky M, Shulman-Peleg A, Nussinov R, Wolfson H.J. The Multiple Common Point Set Problem and its Application to Molecule Binding Pattern Detection, J. Comp. Biol., 2006, Vol 13, pp. 407-428.