|Multiple Alignment of Protein-Protein InterfaceS (PPIs)|
|Recognizes spatially conserved chemical interactions shared by a set of PPIs|
1 - If the chain IDs are known use the following format [PDB] [chain 1]:[chain 2]:
e.g. 1cse E:I, 1cbw HG:I
This will compare between two interfaces:
PPI 1 - created by chains E and I of 1cse
PPI 2 - created by chains HG interacting with chain I in 1cbw
2 - If the interacting chains are unknown type the PDB codes separated by spaces.
e.g.1cse, 1tgs, 1acb
The advantage of the first option is that it allows to define complex interfaces created by more than a pair of proteins chains (for example chains HG of 1cbw and chain I of 1cbw). However, you should not use it if you are not sure that the chains you type actually interact with each other.
If the second option is used and no chains are specified by the user 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. MAPPIS will compare only the interfaces defined by the selected chains. Files that are uploaded by the user will be handled in a similar manner.
Note: Single chain protein molecules that have no protein binding partner in the submitted PDB file can not be compared by the MAPPIS method
Stage 2 - Process of MAPPIS:
This window shows the process of activation of MAPPIS. 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.
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 3 - Output of MAPPIS:
The window below presents the output of the MAPPIS 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):
The protein chain, followed by the identity of the amino acid
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.
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)
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
The distance in space measured between the matched features.
Marks the features shared by the two molecules that are contributed by residues with the same identity of the amino acid.
Stage 4 - Jmol options:
Each solution can be visualized with Jmol. The default view presents the superimposition of all the complexes as well as the matched interactions and their physico-chemical properties. The molecules are colored by model (according to the order of input molecules, the first is red and blue, the second is lighter red and lighter blue etc.). The physico-chemical properties (pseudocenters) are represented as balls and the common interactions are represented by yellow bars. The matched properties are represented only for the first PPI. Hydrogen bond donors are blue, acceptors - red, donors/acceptors - green, hydrophobic aliphatic - orange and aromatic - gray. The interactions are represented by yellow bars. surface points that have a similar location in all the molecules are represented as smaller dots with the same coloring.
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.
Please don't hesitate to contact if you have further problems or questions: firstname.lastname@example.org
Reference: Shulman-Peleg A, Shatsky M, Nussinov R. and Wolfson H.J. Spatial chemical conservation of hot spot interactions in protein-protein complexes. BMC Biol. 2007 Oct 9;5(1):43