News & Events
Protein –Protein Interaction Saga
- April 10, 2018
- Posted by: rasa
- Category: Molecular Modelling & Simulation
Protein-Protein docking is a kind of bioinformatics tool for studying protein-protein interaction. Protein-protein interaction plays important role in biological processes like signal transduction, cellular motion, gene regulation and transport, it is the way to find target for drug discovery. Generally, the protein structures which had high resolution and were determined by X-ray crystallography was considered for docking but recently focus has been shifted towards low resolution proteins.
Protein-protein docking is the prediction of the structure of the protein-protein complex from the structure of the individual proteins. The similarity between proteins of complex can be accessed through comparison or alignment of sequences. There are two instances of protein-protein docking task; first one is bound docking in which proteins in co-crystallized complex are separated and redocked the original complex by a computational method. It does not involve any conformational changes. The second one is unbound docking where protein molecules in their native form. In this case docking algorithm should consider the conformational changes upon binding of two proteins.
There are many online web servers for protein-protein docking. PatchDock is one of important web servers; it performs the structure prediction of protein-protein and protein-small molecule complexes. It is geometry based molecular docking algorithm and is aimed at docking transformation that yield good molecular shape complementary. This transformation induces both wide interfaces and small amount of steric clashes. A wide interface is ensured to include several matched local features of the docked molecules that have complementary characteristics. In PatchDock, molecule is represented in Connolly dot surface and it divided into concave, convex and flat patches. Then, complementary patches are matched to generate candidate transformations. . Each candidate is further evaluated by a scoring function that considers both geometric fit and atomic desolvation energy. Finally, a root mean square deviation clustering is applied to the candidate solutions to discard redundant solutions.
The PatchDock has high efficiency because of its fast transformational search. The input for PatchDock is two molecules in PDB format.The molecules are either uploaded or directly retrieved from Protein Data Bank. User can also enter the PDB code only. If someone wants to dock certain chain/chains of proteins then they should specify the desired chain ID/IDs. The output web page presents the top 20 solutions is automatically generated. The solutions are presented in a table form, a row for each solution. The geometric score, the desolvation energy, the interface area size and actual rigid transformation of the solution are shown. There will be a link to PDB file that presents the docking solution is also present in each line. The user may view or download it. Protein-protein docking can also explain the details of specific interaction at atomic level.
1.Vakser, Ilya A. “Protein-protein docking: From interaction to interactome.” Biophysical journal 107, no. 8 (2014): 1785-1793.
2.Schneidman-Duhovny, Dina, Yuval Inbar, Ruth Nussinov, and Haim J. Wolfson. “PatchDock and SymmDock: servers for rigid and symmetric docking.” Nucleic acids research 33, no. suppl_2 (2005): W363-W367.