Virtual docking

Forino M, Jung D, Easton JB, Houghton PJ, Pellecchia M. Virtual docking approaches to protein kinase B inhibition. J Med Chem 2005 48 2278-81. 

Plate 15 MIF transformation obtained with PathFinder program. Left, the transformation for the NAD site of the protein L-aspartate oxidase. Right, the MIF transformation for the NAD ligand molecule alone. The two maps are very similar, although the NAD molecule was roto-translated from the initial true position. The map comparison obtained from PathFinder can substitute virtual docking procedures. 

The main sonrces for the identification of natural compound functional scaffolds are the public literature, database mining, screening or bioassays, and virtual docking of natural compounds into three-dimensional structures of target proteins (see Chapter 3). 

Table 10.4 3. Common docking tools for virtual screening.

The calculation of the binding affinity with con.sidcration of all tbc.se effects for virtual screening is not possible. In order to circumvent thus difficulty, scoring functions arc used instead, c.g., the Liidi scoring function [80, or consensus scoring functions derived from FlevX score, DOCK score, GOLD score, ChemScore, or PMF score [81 ]. 

Examples of this coordination number are virtually confined to linear Dock complexes of Cu Ag Au and Hg of which a well-known instance is the ammine formed when ammonia is added to an aqueous solution of Ag+ [H3N-Ag-NH3]+... 

If structural information of the protein target is available, e.g., a crystal structure, in silico screening of huge virtual compound libraries can be conducted by the use of docking simulations. Based on identified primary hits, structural variations of the ligand can be evaluated by computational modeling of the ligand-protein complex. 

Virtual screening uses computational docking methods to assess which of a large database of compounds will fit into the unliganded structure of the target protein. Current protocols and methods can, with up to 80% success, predict the binding position and orientation of ligands that are known to bind... 

Kitchen DB, Decornez H, Furr JR, Bajorath J. Docking and scoring in virtual screening for drug discovery methods and applications. Nat Rev Drug Discov 2004 3(ll) 935-49. 

Makino S, Ewing TJ, Kuntz ID. DREAM-r-i- flexible docking program for virtual combinatorial libraries. J Comput Aided Mol Des 1999 13 513-32. 

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