Developing & Benchmarking Large-scale Docking (LSD) Pipeline. Niu Huang, 02/17/2004. LSD pipeline. Model Building (ModBase/PDB). Binding Site Refinement (PLOP/Modeller). LigBase. Post-docking Refinement (PLOP). Ligand Docking (DOCK22.214.171.124). Central Database System. Where are we now?.
Niu Huang, 02/17/2004
Binding Site Refinement
Central Database System
Using focused set of spheres appears to be essential for reducing the noise caused by inaccurate scoring function that favors the wrong docking poses, which is alleviated by only using the spheres filled in hot spot region.
Test1 docked ligands top scored mddr decoys
Test10 docked ligands top scored mddr decoys
DHFR cont. 3
The conformational flexibility of the binding site appears to contribute to the poor enrichment as implicated by crystal structures, however it may be also due to other factors such as, lack of protein desolvation penalty in scoring function.
* Structure, 1997, 5:601-612
Top scored MDDR decoysPARP cont. 1
Multiple binding sub-sites? anything to do with the way to generate dockable database
and the way to match spheres?
Enrichment data sets (known ligands and decoys datasets)
Docking and scoring test sets (experimental structures and binding affinities)