prediction of ligand binding sites
TRANSCRIPT
PREDICTION OF LIGAND BINDING SITES
Amit SinghBioinformaticianCentral University of Punjab
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http://www.ceitec.eu/ceitec-mu/protein-structure-and-dynamics/rg110Weisel,M. et al. (2007) PocketPicker: analysis of ligand binding-sites with shapedescriptors. Chem. Cent. J., 1, 7.
Ligand Binding Sites
These are the sites of activity in proteins usually lie in cavities.
Binding of substrate typically serves as a mechanism for triggering some events like chemical modification or conformational change.
The size and shape of these cavities command the three dimensional geometry of ligands.
Cavities determination is prerequisite for protein ligand docking, structure-based drug design.
•J. Yu, Y. Zhou, I. Tanaka, M. Yao, Roll: A new algorithm for the detection of protein pockets and cavities with a rolling probe sphere. Bioinformatics, 26(1), 46-52, (2010)
Methods for prediction of ligand binding sites.
PocketPicker
PASS. RollLIGSITE
PocketPicker.
5.Preparation of shape descriptors to enable comparisons of different pocket shapes.
4.Clustering of adjoining grid probes(BI 16-26) indicating buried regions of the structure to find potential binding-sites.
3.Calculation of buriedness values of grid probe installed in areas closely above the protein surface.
2.Grid points that exceed maximal distance of 4.5Ao to the closet protein atom are excluded.
1A rectangular grid with 1Ao mesh size is generated around the protein.
Shapes of pocket conformation by PocketPicker.
PASS(Putative Active Sites with Spheres)
Schematic illustration of Roll: Slice of the grid system.
Jian Yu et al. Bioinformatics 2010;26:46-52
Roll
Volume depth.
Jian Yu et al. Bioinformatics 2010;26:46-52
LIGSITE
1. Protein is projected onto a 3D grid and grid points are labelled as protein,surface,solvent.
2. Sequence of grid points starts and ends with surface grid points and which has solvent grid point in between is identified.
3. Number of surface -solvent-surface event of each solvent grid is recorded.
4. A minimum threshold for surface -solvent-surface event is applied to solvent grid to mark them as pocket.
5. Clustering of pocket grid points and ranked by no. of grid points.
References
Brady GP, Stouten PFW: Fast prediction and visualization of protein binding pockets with PASS. J Comput-Aided Mol Des 2000, 14:383-401.
Weisel,M. et al. (2007) PocketPicker: analysis of ligand binding-sites with shape descriptors. Chem. Central J., 1, 7–23.
Jian Yu, Yong Zhou, Isao Tanaka: Roll: a new algorithm for the detection of protein pockets and cavities with a rolling probe sphere. Bioinformatics, (2010) 26(1):46-52.
Huang,B. and Schroeder,M. (2006) LIGSITEcsc: predicting ligand binding sites using the Connolly surface and degree of conservation. BMC Struct. Bio., 6, 19.